Publications by authors named "Xian-Bao Liu"

30 Publications

  • Page 1 of 1

Myocardial infarction detected by a smartwatch after transcatheter aortic valve replacement during the COVID-19 pandemic.

World J Emerg Med 2021 ;12(3):247-248

Department of Cardiology, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188292PMC
January 2021

A case of a successful post-transcatheter aortic valve replacement His bundle pacing.

World J Emerg Med 2021 ;12(2):157-159

Department of Cardiology, the Second Affi liated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947553PMC
January 2021

Sex differences in patients undergoing transcatheter aortic valve replacement in Asia.

Open Heart 2021 01;8(1)

Department of Cardiology, Sichuan University West China Hospital, Chengdu, China.

Objectives: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.

Methods: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.

Results: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.

Conclusions: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
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http://dx.doi.org/10.1136/openhrt-2020-001541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798412PMC
January 2021

Post-dilatation improves stent apposition in patients with ST-segment elevation myocardial infarction receiving primary percutaneous intervention: A multicenter, randomized controlled trial using optical coherence tomography.

World J Emerg Med 2020 ;11(2):87-92

Department of Cardiology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI.

Methods: The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI.

Results: There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE).

Conclusion: In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifier: NCT02121223).
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2020.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010524PMC
January 2020

The first two cases of transcatheter mitral valve repair with ARTO system in Asia.

World J Emerg Med 2020 ;11(1):33-36

Cardiovascular Department, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Background: MAVERIC (Mitral Valve Repair Clinical Trial) validates the safety and efficacy of the ARTO system. We here report the first two successful cases of utilizing the ARTO system in patients with symptomatic heart failure (HF) with functional mitral regurgitation (FMR) in Asia.

Methods: Two patients, aged 70 and 63, had severe HF with FMR. Transesophageal echocardiography confirmed that the left ventricular ejection fractions were less than 50% with severe mitral regurgitation (MR) in both patients. Optimizing drug treatment could not mitigate their symptoms. Therefore, we used the ARTO system to repair the mitral valve for these patients on March 5 and 6, 2019, respectively.

Results: Mitral valve repairs using the ARTO system were successfully performed under general anaesthesia for these two patients. MR was decreased immediately after the procedures in both patients. The 30-day and 3-month transthoracic echocardiography (TTE) revealed a moderate to severe MR in both patients, and the New York Heart Association (NYHA) scales were also partially improved.

Conclusion: The first two cases in Asia indicate that the ARTO system is feasible for patients with heart failure with FMR, and the patient selection appears to be crucial.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885581PMC
January 2020

Ascending aortic dilatation rate after transcatheter aortic valve replacement in patients with bicuspid and tricuspid aortic stenosis: A multidetector computed tomography follow-up study.

World J Emerg Med 2019 ;10(4):197-204

Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Background: Current data is lacking about the progression of ascending aortic dilatation after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). This study aims to assess the ascending aortic dilatation rate (mm/year) after TAVR in patients with BAV versus TAV using a multidetector computed tomography (MDCT) follow-up and to determine the predictors of ascending aortic dilatation rate.

Methods: Severe AS patients undergoing TAVR from March 2013 to March 2018 at our center with MDCT follow-ups were included. BAV and TAV were identified using baseline MDCT. Baseline and follow-up MDCT images were analyzed, and the diameters of ascending aorta were measured. Study end point is ascending aortic dilatation rate (mm/year). Furthermore, factors predicting ascending aortic dilatation rate were also investigated.

Results: Two hundred and eight patients were included, comprised of 86 BAV and 122 TAV patients. Five, 4, 3, 2, and 1-year MDCT follow-ups were achieved in 7, 9, 30, 46, and 116 patients. The ascending aortic diameter was significantly increased after TAVR in both BAV group (43.7±4.4 mm vs. 44.0±4.5 mm; P<0.001) and TAV group (39.1±4.8 mm vs. 39.7±5.1 mm; P<0.001). However, no difference of ascending aortic dilatation rate was found between BAV and TAV group (0.2±0.8 mm/year vs. 0.3±0.8 mm/year, P=0.592). Multivariate linear regression revealed paravalvular leakage (PVL) grade was independently associated with ascending aortic dilatation rate in the whole population and BAV group, but not TAV group. No aortic events occurred during follow-ups.

Conclusion: Ascending aortic size continues to grow after TAVR in BAV patients, but the dilatation rate is mild and comparable to that of TAV patients. PVL grade is associated with ascending aortic dilatation rate in BAV patients post-TAVR.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732170PMC
January 2019

The first four cases of successful NeoChord procedure in mainland China.

World J Emerg Med 2019 ;10(3):133-137

Cardiovascular Department, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Background: Transapical off-pump NeoChord procedure is a novel minimally invasive surgical repair of degenerative mitral regurgitation (MR). Here, we report the first four cases of NeoChord procedure in patients with mitral valve prolapse in mainland China.

Methods: Four patients, aged 86, 84, 80 and 60 years, with severe MR due to posterior middle scallop prolapse (P2), underwent transapical off-pump artificial chordae implantation on April 9 and 10, 2019. The procedure was performed by left mini-thoracotomy under general anaesthesia and guided by 2D and 3D dimensional transoesophageal echocardiography (TEE).

Results: Mitral valve repair via NeoChord procedure was successfully performed with implantation of 3 artificial chordae in the first patient and 3, 2, and 3 artificial chordae in the following patients, respectively. Intraoperative TEE and pre-discharge transthoracic echocardiography (TTE) showed only mild to moderate MR of these four patients and no postoperative complications were noted. There were no changes of TTE finding between one-month follow-up and pre-discharge.

Conclusion: The successful NeoChord procedures in four Chinese indicate that the valve repair using the NeoChord system for Chinese population is feasible.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545367PMC
January 2019

Regulation of Vascular Calcification by Growth Hormone-Releasing Hormone and Its Agonists.

Circ Res 2018 05 4;122(10):1395-1408. Epub 2018 Apr 4.

From the Departments of Cardiology (J.S., N.Z., Y.-N.L., P.P.X., X.-b.L., X.-y.H., W.Z., J.W., H.Y.)

Rationale: Vascular calcification (VC) is a marker of the severity of atherosclerotic disease. Hormones play important roles in regulating calcification; estrogen and parathyroid hormones exert opposing effects, the former alleviating VC and the latter exacerbating it. To date no treatment strategies have been developed to regulate clinical VC.

Objective: The objective of this study was to investigate the effect of growth hormone-releasing hormone (GHRH) and its agonist (GHRH-A) on the blocking of VC in a mouse model.

Methods And Results: Young adult osteoprotegerin-deficient mice were given daily subcutaneous injections of GHRH-A (MR409) for 4 weeks. Significant reductions in calcification of the aortas of MR409-treated mice were paralleled by markedly lower alkaline phosphatase activity and a dramatic reduction in the expression of transcription factors, including the osteogenic marker gene and its downstream factors, osteonectin and osteocalcin. The mechanism of action of GHRH-A was dissected in smooth muscle cells isolated from human and mouse aortas. Calcification of smooth muscle cells induced by osteogenic medium was inhibited in the presence of GHRH or MR409, as evidenced by reduced alkaline phosphatase activity and Runx2 expression. Inhibition of calcification by MR409 was partially reversed by MIA602, a GHRH antagonist, or a GHRH receptor-selective small interfering RNA. Treatment with MR409 induced elevated cytosolic cAMP and its target, protein kinase A which in turn blocked nicotinamide adenine dinucleotide phosphate oxidase activity and reduced production of reactive oxygen species, thus blocking the phosphorylation of nuclear factor κB (p65), a key intermediate in the ligand of receptor activator for nuclear factor-κ B-Runx2/alkaline phosphatase osteogenesis program. A protein kinase A-selective small interfering RNA or the chemical inhibitor H89 abolished these beneficial effects of MR409.

Conclusions: GHRH-A controls osteogenesis in smooth muscle cells by targeting cross talk between protein kinase A and nuclear factor κB (p65) and through the suppression of reactive oxygen species production that induces the gene and alkaline phosphatase. Inflammation-mediated osteogenesis is thereby blocked. GHRH-A may represent a new pharmacological strategy to regulate VC.
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http://dx.doi.org/10.1161/CIRCRESAHA.117.312418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948169PMC
May 2018

Effect of corticosteroids on atrial fibrillation after catheter ablation: a meta-analysis.

J Zhejiang Univ Sci B 2018 Jan.;19(1):57-64

Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Objective: The purpose of this meta-analysis was to explore the effect of corticosteroids on atrial fibrillation (AF) following catheter ablation.

Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for published articles describing the effect of corticosteroids in preventing AF recurrence after catheter ablation. Data on study and patient were extracted. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by use of a random-effect model, and P values of <0.05 were considered significant.

Results: Two randomized controlled trials (RCTs) and three cohort studies involving 846 patients were included in this meta-analysis. Within one month of catheter ablation, corticosteroid use was associated with a declined risk of recurrence of AF in RCT (RR 0.57, 95% CI 0.39 to 0.85, P=0.005), but without significant effect in cohort studies (RR 1.01, 95% CI 0.79 to 1.30, P=0.94). After three months of catheter ablation, corticosteroids did not have a significant effect in the prevention of late recurrence of AF in either RCT (RR 0.78, 95% CI 0.38 to 1.59, P=0.49) or cohort studies (RR 0.96, 95% CI 0.70 to 1.31, P=0.78).

Conclusions: Our meta-analysis suggested that periprocedural administration of corticosteroids of catheter ablation was associated with reduction of early but not late recurrence of AF.
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http://dx.doi.org/10.1631/jzus.B1600529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802978PMC
August 2018

First-in-man implantation of the retrievable and repositionable VenusA-Plus valve.

World J Emerg Med 2018 ;9(1):64-66

Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: No retrievable and repositionable second generation transcatheter aortic valve is available in China. Here, we report the first-in-man implantation of the retrievable and repositionable VenusA-Plus valve.

Methods: A 76-year-old patient with symptomatic severe aortic stenosis and high surgical risk (STS 13.8%) was recommended for transcatheter aortic valve replacement (TAVR) by heart valve team. Type 0 bicuspid aortic valve with asymmetric calcification was identified by dual source computed tomography, and the unfavorable anatomies increased the possibility of malposition and paravalvular leakage during TAVR. Therefore, we used the retrievable and repositionable VenusA-Plus valve for the patient.

Results: Transfemoral TAVR was performed under local anesthesia with sedation, and a 26mm VenusA-Plus valve was successfully implanted. No transvalvular pressure gradient and trace paravalvular leakage were found.

Conclusion: The successful first-in-man implantation indicates the retrievable and repositionable VenusA-Plus valve is feasible in complicated TAVR cases such as bicuspid aortic valve.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2018.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717379PMC
January 2018

Dexmedetomidine mitigates isoflurane-induced neurodegeneration in fetal rats during the second trimester of pregnancy.

Neural Regen Res 2017 Aug;12(8):1329-1337

Department of Anesthesia, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China.

Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.
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http://dx.doi.org/10.4103/1673-5374.213554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607829PMC
August 2017

Bispectral index-guided sedation in transfemoral transcatheter aortic valve implantation: a retrospective control study.

J Zhejiang Univ Sci B 2017 Apr.;18(4):353-359

Department of Anesthesia, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Objective: Transcatheter aortic valve implantation (TAVI) is a minimally invasive therapy for elderly patients with severe aortic valve stenosis who were refused surgical aortic valve replacement because of the high perioperative risk. Traditionally, this procedure has been done under general anesthesia, but more recently local anesthesia and sedation have become popular. This research assessed the effectiveness of transfemoral TAVI under bispectral index (BIS)-guided sedation.

Methods: In this single-center retrospective control analysis, clinical data, including demographic characteristics, echocardiography, periprocedural data, and main complications, were collected and assessed in 113 patients undergoing TAVI through the femoral artery under general anesthesia (GA group, n=36) and under BIS-guided sedation (SED group, n=77).

Results: The demographic characteristics and echocardiographic parameters between the two groups were similar (P>0.05). Two (2.6%) of patients were moved from BIS-guided sedation to general anesthesia for surgical reasons. Procedures were significantly shorter in the SED group than in the GA group ((127.10±44.43) min vs. (165.90±71.62) min, P=0.004). Patients in the SED group lost less blood and received significantly fewer red blood cells and catecholamines than those in the GA group (5.19% vs. 22.22%, P=0.017 and 67.53% vs. 97.22%, P<0.001). The length of hospital stay was significantly shorter and there were fewer pulmonary complications in the SED group than in the GA group. Thirty-day mortality was similar between the two groups.

Conclusions: BIS-guided sedation is a feasible and safe approach for transfemoral TAVI. The anesthesiologist should choose the best anesthetic method according to the team's experience.
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http://dx.doi.org/10.1631/jzus.B1600522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394100PMC
September 2017

A hospital-based survey of patients with severe valvular heart disease in China.

Int J Cardiol 2017 Mar 25;231:244-247. Epub 2016 Nov 25.

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address:

Objectives: Due to increasing aging, the epidemiology of VHD may have changed in China. This study aimed to provide contemporary information on the prevalence, distribution patterns, and etiology of severe VHD in China.

Methods: This was a retrospective survey at Second Affiliated Hospital of Zhejiang University, which included all consecutive patients between 2010 and 2015.

Results: In all, 139,496 patients were enrolled. Among severe valve diseases, MR was the most frequent (n=946, 0.68%) followed by MS (n=524, 0.38%), AS (n=392, 0.28%), and AR (n=371, 0.27%). Severe MR and AS prevalence rates increased strikingly with age. Rheumatic heart disease had an prevalence of 1.56% (n=2179), and remained one of the most common causes of severe VHD in patients younger than 65years old (99.5% of MS with rheumatic; 27.6% of MR with rheumatic; 25.7% of AS with rheumatic; 31.6% of AR with rheumatic). Aortic valve calcification was the predominant AS etiology, and its prevalence greatly increased with age. In severe AR, rheumatic fever was the most common etiology in patients below 65; in those above 65, etiology was mostly degenerative. In severe primary MR, mitral valve prolapse was the most common cause. Prevalence of secondary MR increased with age, from 16.4% in 18-44years old to 51.7% in individuals ≥75.

Conclusions: Severe valvular diseases are very common; rheumatic fever and degenerative valvular changes remain predominant causes in patients below 65 and older ones, respectively. Young adults present mainly with primary MR, while secondary MR is more common in elderly ones.
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http://dx.doi.org/10.1016/j.ijcard.2016.11.301DOI Listing
March 2017

Roles of SIRT3 in heart failure: from bench to bedside.

J Zhejiang Univ Sci B 2016 Nov.;17(11):821-830

Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Heart failure (HF) represents the most common endpoint of most cardiovascular diseases (CVDs) which are the leading causes of death around the world. Despite the advances in treating CVDs, the prevalence of HF continues to increase. It is believed that better results of prognosis are obtained from prevention rather than additional treatment for HF. Therefore, it is reasonable to prevent the development of CVDs or other complications to HF. Most types of HF are attributed to contractile dysfunction, cardiac hypertrophy or remodeling, and ischemic injuries. SIRT3 is a mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase whose substrates vary from metabolic biogenesis-associated proteins to stress-responsive proteins. In recent years, a number of studies have highlighted the cardio-protective role of SIRT3 and, as such, efforts have been made to induce over-expression or increased activity of this protein. In this review, we provide an overview of the roles of SIRT3 in cardiac hypertrophy induced by pressure overload or agonists and cardiomyocytes ischemic injuries. Moreover, we will introduce the application of SIRT3 agonists in the prevention of cardiac hypertrophy and ischemia reperfusion injury.
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http://dx.doi.org/10.1631/jzus.B1600253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120224PMC
June 2017

Fractional Flow Reserve Guided Percutaneous Coronary Intervention Improves Clinical Outcome with Reduced Cost in Contemporary Clinical Practice.

Chin Med J (Engl) 2015 Aug;128(15):2000-5

Department of Cardiology, Second Affiliated Hospital, College of Medicine; Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.

Background: Fractional flow reserve (FFR) is currently considered as the gold standard for evaluating the functional significance of coronary stenosis. However, its potential benefits in real-world practice remain unknown in China. This study aimed to test the hypothesis that the use of FFR is associated with improved outcome and reduced cost in Chinese real-world clinical practice.

Methods: A retrospective cohort study was carried out using the database of Second Affiliated Hospital of Zhejiang University, a tertiary and high-volume center in China. Clinical events were compared using the Cox proportional hazards model during a median follow-up of 13 months.

Results: The study cohort consisted of 366 consecutive patients referred for coronary revascularization with adjunct FFR and 366 matched controls, from 2010 to 2014. Major adverse cardiac events (MACEs) (death, myocardial infarction, repeated revascularization, or hospitalization for angina) at 4 years were found in 12.0% of angiography-guided patients and 4.9% in the FFR-guided group (P < 0.001). The mean number of implanted stents was significantly lower in FFR treated subjects (0.52 ± 0.82 stents) compared with the angiography-guided group (0.93 ± 0.96 stents) (P < 0.001). No difference in overall costs at initial hospitalization was observed between angiography-guided percutaneous coronary intervention (PCI) compared with FFR-guided PCI (RMB 33,000 Yuan, range: RMB 7393-44,700 Yuan) versus RMB 21,200 Yuan (RMB 19,100-47,100 Yuan) (P = 0.54). However, costs for MACEs during follow-up were significantly reduced in the FFR-guided arm (P < 0.001).

Conclusions: In the contemporary clinical practice, FFR-guided PCI is associated with decreased use of stents, improved clinical outcome, and reduced costs, compared with angiography-guided PCI.
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http://dx.doi.org/10.4103/0366-6999.161341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717962PMC
August 2015

Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians.

J Zhejiang Univ Sci B 2015 May;16(5):370-9

Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Background: A lot of studies have demonstrated that C242T polymorphism in CYBA genes may play an important role in the pathological process of acute coronary syndrome (ACS). However, the results are not consistent. To further evaluate this debate, we performed a meta-analysis to determine the relationship between C242T polymorphism and ACS.

Methods And Results: We screened PubMed/MEDLINE, EBSCIO, and EMBASE research reports until Mar. 2014 and extracted data from 10 studies involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity documented a significant decreased risk of ACS for C242T polymorphism in the Asian population under allelic comparison (odd ratio (OR) 0.73; 95% confidence intervals (CI) 0.64-0.83), dominant model (OR 0.71; 95% CI 0.62-0.82), and homozygote comparison (OR 0.57; 95% CI 0.35-0.92). However, in the overall population and especially with Caucasians, no significant association was uncovered. Further meta-regression analysis revealed that the heterogeneity among studies was largely attributed to ethnicity. No publication bias was detected through a funnel plot and an Egger's linear regression test.

Conclusions: Taken together, our results suggest that the C242T polymorphism might be a protective factor against developing ACS in the Asian population. Further researches will be needed to identify the confounding factors which modified the protective effect of T allele among Caucasians.
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http://dx.doi.org/10.1631/jzus.B1400241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432989PMC
May 2015

Evaluation of the safety and efficacy of transcatheter aortic valve implantation in patients with a severe stenotic bicuspid aortic valve in a Chinese population.

J Zhejiang Univ Sci B 2015 Mar;16(3):208-14

Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Radiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Echocardiography, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Cardiosurgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Objective: The purpose of this study is to evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with a severe stenotic bicuspid aortic valve (BAV) in a Chinese population. While several groups have reported the feasibility, efficacy, and safety of TAVI for patients with a BAV, worldwide experience of the technique is still limited, especially in China.

Methods: From March 2013 to November 2014, high surgical risk or inoperable patients with symptomatic severe aortic stenosis (AS) who had undergone TAVI at our institution were selected for inclusion in our study. RESULTS were compared between a BAV group and a tricuspid aortic valve (TAV) group.

Results: Forty patients were included in this study, 15 (37.5%) of whom were identified as having a BAV. In the BAV group, the aortic valve area was smaller ((0.47±0.13) vs. (0.59±0.14) cm(2)), the ascending aortic diameter was larger ((40.4±4.4) vs. (36.4±4.3) mm), and the concomitant aortic regurgitation was lower. No significant differences were found between the groups in the other baseline characteristics. No differences were observed either in the choice of access or valve size. The procedural success achieved in this study was 100%. There were no differences between groups in device success (86.7% vs. 88.0%), 30-d mortality (6.7% vs. 8.0%), or 30-d combined end point (13.3% vs. 12.0%). The incidences of new pacemaker implantation, paravalvular regurgitation and other complications, recovery of left ventricle ejection fraction and heart function were similar in both groups.

Conclusions: Patients with a severely stenotic BAV can be treated with TAVI, and their condition after treatment should be similar to that of people with a TAV.
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http://dx.doi.org/10.1631/jzus.B1500017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357370PMC
March 2015

Preconditioning of bone marrow mesenchymal stem cells by prolyl hydroxylase inhibition enhances cell survival and angiogenesis in vitro and after transplantation into the ischemic heart of rats.

Stem Cell Res Ther 2014 Sep 25;5(5):111. Epub 2014 Sep 25.

Introduction: Poor cell survival and limited functional benefits have restricted the efficacy of bone marrow mesenchymal stem cells (BMSCs) in the treatment of myocardial infarction. We showed recently that hypoxia preconditioning of BMSCs and neural progenitor cells before transplantation can enhance the survival and therapeutic properties of these cells in the ischemic brain and heart. The present investigation explores a novel strategy of preconditioning BMSCs using the Hypoxia-inducible factor 1α (HIF-α) prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG) to enhance their survival and therapeutic efficacy after transplantation into infarcted myocardium.

Methods: BMSCs from green fluorescent protein transgenic rats were cultured with or without 1 mM DMOG for 24 hours in complete culture medium before transplantation. Survival and angiogenic factors were evaluated in vitro by trypan blue staining, Western blotting, and tube formation test. In an ischemic heart model of rats, BMSCs with and without DMOG preconditioning were intramyocardially transplanted into the peri-infarct region 30 minutes after permanent myocardial ischemia. Cell death was measured 24 hours after engraftment. Heart function, angiogenesis and infarct size were measured 4 weeks later.

Results: In DMOG preconditioned BMSCs (DMOG-BMSCs), the expression of survival and angiogenic factors including HIF-1α, vascular endothelial growth factor, glucose transporter 1 and phospho-Akt were significantly increased. In comparison with control cells, DMOG-BMSCs showed higher viability and enhanced angiogenesis in both in vitro and in vivo assays. Transplantation of DMOG-BMSCs reduced heart infarct size and promoted functional benefits of the cell therapy.

Conclusions: We suggest that DMOG preconditioning enhances the survival capability of BMSCs and paracrine effects with increased differentiation potential. Prolyl hydroxylase inhibition is an effective and feasible strategy to enhance therapeutic efficacy and efficiency of BMSC transplantation therapy after heart ischemia.
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http://dx.doi.org/10.1186/scrt499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535299PMC
September 2014

Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and refractory to sevoflurane-induced protection.

PLoS One 2013 4;8(10):e76652. Epub 2013 Oct 4.

Department of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejaing, China.

Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076652PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790738PMC
May 2014

Update of transcatheter valve treatment.

J Zhejiang Univ Sci B 2013 Aug;14(8):670-5

Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Transcatheter valve implantation or repair has been a very promising approach for the treatment of valvular heart diseases since transcatheter aortic valve implantation (TAVI) was successfully performed in 2002. Great achievements have been made in this field (especially TAVI and transcatheter mitral valve repair--MitraClip system) in recent years. Evidence from clinical trials or registry studies has proved that transcatheter valve treatment for valvular heart diseases is safe and effective in surgical high-risk or inoperable patients. As the evidence accumulates, transcatheter valve treatment might be an alterative surgery for younger patients with surgically low or intermediate risk valvular heart diseases in the near future. In this paper, the updates on transcatheter valve treatment are reviewed.
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http://dx.doi.org/10.1631/jzus.BQICC702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735966PMC
August 2013

Hypercholesterolemia blocked sevoflurane-induced cardioprotection against ischemia-reperfusion injury by alteration of the MG53/RISK/GSK3β signaling.

Int J Cardiol 2013 Oct 12;168(4):3671-8. Epub 2013 Jul 12.

Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address:

Background: Recent studies have demonstrated that volatile anesthetic preconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats.

Methods: Normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane during three 5 min periods with and without PI3K antagonist wortmannin (10 μg/kg, Wort) or the ERK inhibitor PD 98059 (1 mg/kg, PD). The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined.

Results: Two hundred and six rats were analyzed in the study. In the healthy rats, sevoflurane significantly reduced infarct size by 42%, a phenomenon completely reversed by wortmannin and PD98059 and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β. In the hypercholesterolemic rats, sevoflurane failed to reduce infarct size and increase the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts.

Conclusions: Hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.
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http://dx.doi.org/10.1016/j.ijcard.2013.06.037DOI Listing
October 2013

Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts.

J Zhejiang Univ Sci B 2013 Jun;14(6):511-7

Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo. Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into six groups (n=12): a sham-operation group, an I/R group, and four sevoflurane postconditioning groups (S2, S5, S10, and S15). In the S2, S5, S10, and S15 groups, the duration times of sevoflurane administration were 2, 5, 10, and 15 min after the onset of reperfusion, respectively. The isolated rat hearts were mounted on the Langendorff system, and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion. Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30, 60, 90, and 120 min of reperfusion were analyzed. Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group). Compared with the I/R group, the S5, S10, and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and the maximal rate of rise or fall of the LV pressure (±dP/dtmax), and decreased myocardial infarct size (P<0.05), but not the S2 group. After 15 min of reperfusion, the expression of p-Akt was markedly up-regulated in the S5, S10, and S15 groups compared with that in the I/R group (P<0.05), but not in the S2 group. Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.
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http://dx.doi.org/10.1631/jzus.B1200195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682167PMC
June 2013

Complex coronary lesions and rotational atherectomy: one hospital's experience.

J Zhejiang Univ Sci B 2012 Aug;13(8):645-51

Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Objective: To evaluate the safety and effectiveness of rotational atherectomy followed by drug eluting stent (DES) implantation in patients with complex coronary lesions.

Methods: From August 2006 to August 2012, 253 consecutive patients with 289 lesions and who underwent rotational atherectomy in our center were enrolled in this study.

Results: The overall procedure success rate was 98% with the cost of two (0.8%) coronary perforations, three (1.2%) dissections, five (2.0%) slow flows or no flows, three (1.2%) peri-procedure myocardial infarctions, and two (0.8%) in hospital deaths. During follow-up (mean three years), one (0.4%) patient died, two (0.8%) patients had acute myocardial infarction, 14 (5.5%) had restenosis, and target lesion revascularization occurred in eight patients (3.2%).

Conclusions: Rotational atherectomy followed by DES implantation is a safe and effective technique for patients with complex coronary lesions, especially calcified and non-dilatable lesions.
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http://dx.doi.org/10.1631/jzus.B1201008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411098PMC
August 2012

Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation.

J Zhejiang Univ Sci B 2012 Aug;13(8):616-23

Cardiovascular Key Lab of Zhejiang Province, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Objective: Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation.

Methods: MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson's trichrome staining, respectively.

Results: Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group.

Conclusions: Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.
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http://dx.doi.org/10.1631/jzus.B1201004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411094PMC
August 2012

Nerve growth factor induces cord formation of mesenchymal stem cell by promoting proliferation and activating the PI3K/Akt signaling pathway.

Acta Pharmacol Sin 2011 Dec;32(12):1483-90

Cardiovascular Key Lab of Zhejiang Province, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Aim: To investigate whether nerve growth factor (NGF) induced angiogenesis of bone marrow mesenchymal stem cells (MSCs) and the underlying mechanisms.

Methods: Bone marrow MSCs were isolated from femors or tibias of Sprague-Dawley rat, and cultured. The cells were purified after 3 to 5 passages, seeded on Matrigel-coated 24-well plates and treated with NGF. Tube formation was observed 24 h later. Tropomyosin-related kinase A (TrkA) and p75NTR gene expression was examined using PCR analysis and flow cytometry. Growth curves were determined via cell counting. Expression of VEGF and pAkt/Akt were analyzed with Western blot.

Results: NGF (25, 50, 100 and 200 μg/L) promoted tube formation of MSCs. The tubular length reached the maximum of a 2.24-fold increase, when the cells were treated with NGF (50 μg/L). NGF (50 μg/L) significantly enhanced Akt phosphorylation. Pretreatment with the specific PI3K inhibitor LY294002 (10 μmol/L) blocked NGF-stimulated Akt phosphorylation, tube formation and angiogenesis. NGF (25-200 μg/L) did not affect the expression of TrkA and vascular endothelial growth factor (VEGF), but significantly suppressed the expression of p75NTR. NGF (50 μg/L) markedly increased the proliferation of MSCs.

Conclusion: NGF promoted proliferation of MSCs and activated the PI3K/Akt signaling pathway, which may be responsible for NGF induction of MSC angiogenesis.
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http://dx.doi.org/10.1038/aps.2011.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010210PMC
December 2011

Tongxinluo promotes mesenchymal stem cell tube formation in vitro.

J Zhejiang Univ Sci B 2011 Aug;12(8):644-51

Cardiovascular Key Lab of Zhejiang Province, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Objective: To study whether Tongxinluo (TXL) can induce angiogenesis in bone marrow mesenchymal stem cells (MSCs), and to investigate the underlying mechanism.

Methods: Bone marrow MSCs were obtained from male Sprague-Dawley rats. We established an angiogenesis model in vitro via matrigel experiment. MSCs were seeded on matrigel coated 24-well plates, and treated by TXL 50 and 100 mg/L. After 24 h, we observed the tube formations of MSCs in the matrigel. Cell migration ability was examined by wound scratch test and transwell assay. Expressions of vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed at the protein level by Western blot. Gelatin zymography assay was applied to investigating the MSC paracrine abilities of pro-MMP-2 and activated MMP-2.

Results: TXL promoted MSC tube formation in matrigel. The ratio of TXL 100 mg/L treated-MSC tubular length was increased 3.04-fold compared to the control group (P<0.05). Scratch test and transwell assay showed that TXL could improve the cell migration ability of MSCs. Western blot experiments showed that TXL promoted MSC synthesis of MMP-2, but it had no influence on the expressions of MMP-9 and TIMP-2. This effect was confirmed by gelatin zymography assay, which showed that TXL increased MSC secretion of pro-MMP-2 and activated MMP-2. VEGF expression of TXL treated-MSCs was increased compared to the control group. The expression of Flk-1 was not different among the groups.

Conclusions: This study demonstrates that TXL can promote the tube formation of MSCs, and the underlying mechanisms are associated with increased migration ability of MSCs and the up-regulation of MMP-2 and VEGF expressions.
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http://dx.doi.org/10.1631/jzus.B1101005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150718PMC
August 2011

Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways.

J Zhejiang Univ Sci B 2010 Aug;11(8):608-17

Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Mesenchymal stem cell (MSC) transplantation has shown a therapeutic potential to repair the ischemic and infracted myocardium, but the effects are limited by the apoptosis and loss of donor cells in host cardiac microenvironment. The aim of this study is to explore the cytoprotection of heat shock protein 90 (Hsp90) against hypoxia and serum deprivation-induced apoptosis and the possible mechanisms in rat MSCs. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric analysis with annexin V/PI staining. The gene expression of Toll-like receptor-4 (TLR-4) and V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ErbB2) was detected by real-time polymerase chain reaction (PCR). The protein levels of cleaved caspase-3, Bcl-2, Bcl-xL, Bax, total-ERK, phospho-ERK, total-Akt, phospho-Akt, and Hsp90 were detected by Western blot. The production of nitric oxide was measured by spectrophotometric assay. Hsp90 improves MSC viability and protects MSCs against apoptosis induced by serum deprivation and hypoxia. The protective role of Hsp90 not only elevates Bcl-2/Bax and Bcl-xL/Bax expression and attenuates cleaved caspase-3 expression via down-regulating membrane TLR-4 and ErbB2 receptors and then activating their downstream PI3K/Akt and ERK1/2 pathways, but also enhances the paracrine effect of MSCs. These findings demonstrated a novel and effective treatment strategy against MSC apoptosis in cell transplantation.
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http://dx.doi.org/10.1631/jzus.B1001007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916094PMC
August 2010

Prolyl hydroxylase inhibitor dimethyloxalylglycine enhances mesenchymal stem cell survival.

J Cell Biochem 2009 Apr;106(5):903-11

Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Mesenchymal stem cell (MSC) transplantation is a promising approach in the therapy of ischemic heart or CNS diseases; however, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. Prolyl hydroxylase inhibition followed by HIF-1alpha up-regulation participates in the regulation of apoptosis and cell survival, which have been shown in cancer cells and neurons. The role of prolyl hydroxylase inhibition by dimethyloxalylglycine (DMOG) in regulation of cell survival has not been investigated in MSCs. In the present investigation with MSCs, apoptosis and cell death induced by serum deprivation were assessed by caspase-3 activation and trypan blue staining, respectively. The mitochondrial apoptotic pathway and PI3K/Akt cell survival pathway were evaluated. DMOG significantly attenuated apoptosis and cell death of MSCs, stabilized HIF-1alpha and induced downstream glucose transport 1 (Glut-1) synthesis. DMOG treatment reduced mitochondrial cytochrome c release, nuclear translocation of apoptosis inducing factor (AIF), and promoted Akt phosphorylation. A specific PI3K inhibitor, wortmannin, blocked Akt phosphorylation and abrogated the beneficial effect of DMOG. These data suggest that the DMOG protection of MSCs may provide a novel approach to promote cell survival during cell stress.
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http://dx.doi.org/10.1002/jcb.22064DOI Listing
April 2009

Angiopoietin-1 protects mesenchymal stem cells against serum deprivation and hypoxia-induced apoptosis through the PI3K/Akt pathway.

Acta Pharmacol Sin 2008 Jul;29(7):815-22

Department of Cardiology, Second affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Aim: The angiopoietin-1 (Ang1)/Tie-2 signaling system not only plays a pivotal role in vessel growth, remodeling, and maturation, but also reduces apoptosis of endothelial cells, neurons, and cardiomyocytes. However, relatively little is known as to whether Ang1 has a protective effect on mesenchymal stem cells (MSC). The aim of the present study was to investigate the protective effect of Ang1/Tie-2 signaling on MSC against serum deprivation and hypoxia-induced apoptosis, and to determine the possible mechanisms.

Methods: Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling staining were used to assess the apoptosis of MSC. The expression of Tie-2, Akt, Bcl-2, Bax, and cleaved caspase-9 and -3 was detected by Western blot analysis.

Results: This study showed that MSC expressed Tie-2 receptor, and Ang1 induced Tie-2 receptor phosphorylation. The protective effect of Ang1 on MSC was dose-dependent and peaked at 50 microg/L; however, the soluble Tie-2/Fc fusion protein, which acts as an inhibitor by sequestering Ang1, abrogated the anti-apoptotic effect. Ang1 induced Akt phosphorylation, increased the Bcl-2/Bax ratio, and decreased the activation of caspase-9 and -3. All these effects were attenuated by Tie-2/Fc and a phosphatidylinositol 3 kinase (PI3K) inhibitor, wortmannin.

Conclusion: These results demonstrate that Ang1 can protect MSC against serum deprivation and hypoxia-induced apoptosis; Ang1/Tie-2 signaling and its downstream PI3K/Akt messenger pathway are crucial in the processes leading to MSC survival.
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http://dx.doi.org/10.1111/j.1745-7254.2008.00811.xDOI Listing
July 2008

Expression of heregulin and ErbB receptors in mesenchymal stem cells.

Chin Med J (Engl) 2008 Jan;121(2):155-60

Division of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.

Background: Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction. Type I neuregulins-1, also known as heregulin, can promote the survival of cardiomyocytes and stimulate angiogenesis. The purpose of this study was to investigate the expression of heregulin and ErbB receptors in mesenchymal stem cells, then further detect the secretion of heregulin and the changes in expression of heregulin and ErbB receptors under conditions of serum deprivation and hypoxia.

Methods: Mesenchymal stem cells isolated from bone marrow of 180 g male Sprague-Dawley rats were cultured. Passage 3 cells were detected experimentally by regular reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real time PCR and Western blotting.

Results: Heregulin and ErbB receptors were expressed in mesenchymal stem cells, and all three ErbB receptors mRNA expressions were significantly down-regulated by serum deprivation and hypoxia, but serum deprivation and hypoxia significantly increased the protein expression of heregulin. Serum deprivation and hypoxia more than 12 hours could induce the secretion of heregulin.

Conclusions: Mesenchymal stem cells can express all three ErbB receptors and heregulin. Serum deprivation and hypoxia decrease the mRNA expression of ErbB receptors, increase the expression of heregulin, and activate the secretion of heregulin.
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January 2008
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