Publications by authors named "Wangping Chen"

11 Publications

  • Page 1 of 1

TMSB4 Overexpression Enhances the Potency of Marrow Mesenchymal Stromal Cells for Myocardial Repair.

Front Cell Dev Biol 2021 9;9:670913. Epub 2021 Jun 9.

Department of the Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Objective: The actin-sequestering proteins, thymosin beta-4 (Tβ4) and hypoxia-inducible factor (HIF)-1α, are known to be associated with angiogenesis after myocardial infarction (MI). Herein, we aimed to identify the mechanism of HIF-1α induction by Tβ4 and investigate the effects of bone marrow mesenchymal stromal cells (BMMSCs) transfected with the Tβ4 gene () in a rat model of MI.

Methods: Rat BMMSCs were isolated, cultured, and transfected with the gene by using the lentivirus-mediated method. Rats with surgically induced MI were randomly divided into three groups ( = 9/group); after 1 week, the rats were injected at the heart infarcted border zone with TMSB4-overexpressed BMMSCs (BMMSC-TMSB4 ), wild-type BMMSCs that expressed normal levels of TMSB4 (BMMSC-TMSB4 ), or medium (MI). The fourth group of animals ( = 9) underwent all surgical procedures necessary for MI induction except for the ligation step (Sham). Four weeks after the injection, heart function was measured using transthoracic echocardiography. Infarct size was calculated by TTC staining, and collagen volume was measured by Masson staining. Angiogenesis in the infarcted heart area was evaluated by CD31 immunofluorescence histochemistry. experiments were carried out to observe the effect of exogenous Tβ4 on HIF-1α and explore the various possible mechanism(s).

Results: experiments showed that vascular density 4 weeks after treatment was about twofold higher in BMMSC-TMSB4 -treated animals than in BMMSC-TMSB4 -treated animals ( < 0.05). The cardiac function and infarct size significantly improved in both cell-treatment groups compared to controls. Notably, the cardiac function and infarct size were most prominent in BMMSC-TMSB4 -treated animals (both < 0.05). HIF-1α and phosphorylated HIF-1α (p-HIF-1α) were significantly enhanced by exogenous Tβ4, which was nonetheless blocked by the factor-inhibiting HIF (FIH) promoter (YC-1). The expression of prolyl hydroxylase domain proteins (PHD) was decreased upon treatment with Tβ4 and further decreased with the combined treatment of Tβ4 and FG-4497 (a specific PHD inhibitor).

Conclusion: TMSB4-transfected BMMSCs might significantly improve recovery from myocardial ischemia and promote the generation of HIF-1α and p-HIF-1α the AKT pathway, and inhibit the degradation of HIF-1α the PHD and FIH pathways.
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http://dx.doi.org/10.3389/fcell.2021.670913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221609PMC
June 2021

miR-199a Overexpression Enhances the Potency of Human Induced-Pluripotent Stem-Cell-Derived Cardiomyocytes for Myocardial Repair.

Front Pharmacol 2021 3;12:673621. Epub 2021 Jun 3.

Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.

Mammalian cardiomyocytes exit the cell cycle during the perinatal period, and although cardiomyocytes differentiated from human induced-pluripotent stem cells (hiPSC-CMs) are phenotypically immature, their intrinsic cell-cycle activity remains limited. Thus, neither endogenous cardiomyocytes nor the small number of transplanted hiPSC-CMs that are engrafted by infarcted hearts can remuscularize the myocardial scar. microRNAs are key regulators of cardiomyocyte proliferation, and when adeno-associated viruses coding for microRNA-199a (miR-199a) expression were injected directly into infarcted pig hearts, measures of cardiac function and fibrosis significantly improved, but the treatment was also associated with lethal arrhythmia. For the studies reported here, the same vector (AAV6-miR-199a) was transduced into hiPSC-CMs, and the cells were subsequently evaluated in a mouse model of myocardial infarction. AAV6-mediated miR-199a overexpression increased proliferation in both cultured and transplanted hiPSC-CMs, and measures of left ventricular ejection fraction, fractional shortening, and scar size were significantly better in mice treated with miR-199a-overexpressing hiPSC-CMs than with hiPSC-CMs that had been transduced with a control vector. Furthermore, although this investigation was not designed to characterize the safety of transplanted AAV6-miR-199a-transduced hiPSC-CMs, there was no evidence of sudden death. Collectively, these results support future investigations of miR-199a-overexpressing hiPSC-CMs in large animals.
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http://dx.doi.org/10.3389/fphar.2021.673621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209326PMC
June 2021

Visualization and Identification of Bioorthogonally Labeled Exosome Proteins Following Systemic Administration in Mice.

Front Cell Dev Biol 2021 7;9:657456. Epub 2021 Apr 7.

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.

Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the non-canonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes and resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
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http://dx.doi.org/10.3389/fcell.2021.657456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058422PMC
April 2021

Cardiac Fibroblasts and Myocardial Regeneration.

Front Bioeng Biotechnol 2021 25;9:599928. Epub 2021 Mar 25.

Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, United States.

The billions of cardiomyocytes lost to acute myocardial infarction (MI) cannot be replaced by the limited regenerative capacity of adult mammalian hearts, and despite decades of research, there are still no clinically effective therapies for remuscularizing and restoring damaged myocardial tissue. Although the majority of the cardiac mass is composed of cardiomyocytes, cardiac fibroblasts (CFs) are one type of most numerous cells in the heart and the primary drivers of fibrosis, which prevents ventricular rupture immediately after MI but the fibrotic scar expansion and LV dilatation can eventually lead to heart failure. However, embryonic CFs produce cytokines that can activate proliferation in cultured cardiomyocytes, and the structural proteins produced by CFs may regulate cardiomyocyte cell-cycle activity by modulating the stiffness of the extracellular matrix (ECM). CFs can also be used to generate induced-pluripotent stem cells and induced cardiac progenitor cells, both of which can differentiate into cardiomyocytes and vascular cells, but cardiomyocytes appear to be more readily differentiated from iPSCs that have been reprogrammed from CFs than from other cell types. Furthermore, the results from recent studies suggest that cultured CFs, as well as the CFs present in infarcted hearts, can be reprogrammed directly into cardiomyocytes. This finding is very exciting as should we be able to successfully increase the efficiency of this reprogramming, we could remuscularize the injured ventricle and restore the LV function without need the transplantation of cells or cell products. This review summarizes the role of CFs in the innate response to MI and how their phenotypic plasticity and involvement in ECM production might be manipulated to improve cardiac performance in injured hearts.
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http://dx.doi.org/10.3389/fbioe.2021.599928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026894PMC
March 2021

Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia.

Front Pediatr 2021 19;9:611007. Epub 2021 Feb 19.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

The purpose of this study was to report our experience in the surgical reconstruction of the right ventricular outflow tract in double outlet right ventricle with a major coronary artery crossing the right ventricular outflow tract in the presence of mirror image-dextrocardia. From January 2005 to December 2019, 19 double outlet right ventricle patients (median age 4 years) with mirror image-dextrocardia and a major coronary artery crossing the right ventricular outflow tract received surgical repair. An autologous pericardial patch was used to enlarge the right ventricular outflow tract in four patients without pulmonary stenosis and three patients with mild pulmonary stenosis. A valved bovine jugular venous conduit was added to a hypoplastic native pathway in nine patients, among which six patients with moderate pulmonary stenosis received small-sized bovine jugular venous conduit implantation (diameter ≤ 16 mm). In comparison, a large-sized bovine jugular venous conduit (diameter >16 mm) was adopted in a total of three patients with severe pulmonary stenosis. Finally, three patients with preoperative pulmonary hypertension (mean pulmonary artery pressure ≥40 mmHg) did not undergo further intervention of right ventricular outflow tract due to the adequate outflow tract blood flow. There was no hospital mortality. One patient with sub-pulmonary ventricular septal defect and concomitant severe pulmonary hypertension died from respiratory failure 11 months after the operation. Kaplan-Meier survival was 94% at 5, 10 years. Within a mean echocardiographic follow-up of 6.9 ± 3.6 years, a total of two patients received reintervention due to valvular stenosis of the bovine jugular venous conduit (pressure gradient > 50 mmHg at 4 and 9 years) after surgical operation. Actuarial freedom from reoperation was 90 and 72% at 5 and 10 years, respectively. During the last echocardiographic follow-up phase, all the survivors were in NYHA class I. Double outlet right ventricle with mirror image-dextrocardia is a rare and complicated congenital cardiac malformation. Surgical reconstruction of the right ventricular outflow tract should be individualized based on the degree of pulmonary stenosis and the specific anatomical features of each patient. Reconstructing the pulmonary artery using the various sizes of valved bovine jugular venous conduit is a safe and effective surgical method.
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http://dx.doi.org/10.3389/fped.2021.611007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933223PMC
February 2021

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

Cardiovasc Diagn Ther 2020 Oct;10(5):1200-1215

Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China.

Background: The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up.

Methods: Data of 3,068 patients from March 2011 through June 2019 was retrospectively extracted from The Provincial National Cardiac Database of Xiangya Second Hospital. The activities considered (and costs calculated) were outpatient consultations, hospital admissions, and drug treatment. Quality of life (QoL) questionnaires were also carried out to assess whether concomitant AFib correction procedures increase risk in patients, or improve patient's QoL.

Results: A total of 3,068 patients completed the questionnaires at a minimum of one time-point during the follow-up. The total cost was combined to obtain incremental costs per quality-adjusted life-years (QALYs). The total costs of the AFib catheter ablation group were remarkably higher compared to surgery as usual group. The incremental cost-effectiveness ratio was $76,513,227 (¥542,287,667) per QALY, with an acceptability line graph for cost at 43%.

Conclusions: AFib is an extraordinarily costly and worrisome public health problem. Precision medicine is vital as it provides a platform for the clinical translation of targeted interventions that are designed to help treat and prevent AFib. Thus, to improve the QoL expectancy outcome(s), both therapeutic and surgical interventions should be aimed at addressing the underlying heart disease rather than restoring sinus rhythm.
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http://dx.doi.org/10.21037/cdt-20-574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666964PMC
October 2020

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity.

Front Genet 2020 16;11:571467. Epub 2020 Oct 16.

School of Pharmacy, Binzhou Medical University, Yantai, China.

Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombin-stimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized a direct interaction between NEAT1 and SFPQ.
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http://dx.doi.org/10.3389/fgene.2020.571467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596361PMC
October 2020

Application of Modified Sliding Anastomosis in the Repair of Aortic Coarctation.

Biomed Res Int 2020 14;2020:3805385. Epub 2020 May 14.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Middle Renmin Road 139, Changsha 410000, China.

Objectives: To evaluate the early and midterm results of a modified sliding anastomosis technique in patients with aortic coarctation.

Materials And Methods: In this study, we reported a new repair method and compared the early and midterm outcome(s) with a conventional surgical approach for the management of patients with aortic coarctation. Forty-eight aortic coarctation patients with a narrowed segment length longer than 2 cm were operated at our department's pediatric surgical division. Excision of the coarctation and end-to-end anastomosis was carried out in twenty-five patients (control group). In contrast, a modified sliding technique was used for twenty-three cases in the observation group. Other accompanying cardiac anomalies simultaneously repaired included ventricular septal defect and patent ductus arteriosus. All patients received 1.5-10 years of postoperative echocardiographic follow-up.

Results: This is a retrospective study carried out between January 2005 and June 2018. The study population consisted of forty-eight patients, which included twenty-six male and twenty-two female patients, with an average age of 5.2 ± 1.9 months (range, 28 days to 1 year). There was no mortality. The operative time, the number of intercostal artery disconnection, the drainage volume, and arm-leg systolic pressure gradient postoperation were less in the observation group as compared to the control group ( < 0.05). Also, cases with an anastomotic pressure gradient exceeding 10 mmHg during follow-up were less in the observation group as compared to the control group ( < 0.05). The postoperative complications encountered were chylothorax (control group 2 cases vs. observation group 0) and pulmonary atelectasis (control group 4 cases vs. observation group 1). They all, however, recovered after conservative treatment. Three patients in the control group underwent balloon angioplasty (reintervention) postoperative 2-4 years due to an increase in the anastomotic pressure gradient (>20 mmHg). After reintervention, the anastomotic pressure gradient reduced to 14 mmHg, 15 mmHg, and 17 mmHg, respectively.

Conclusions: For long segment aortic coarctation patients (longer than 2 cm), the use of the modified sliding anastomotic technique effectively helps to retain more autologous tissues, enlarge the diameter of the anastomosis, and decrease anastomotic tension and vascular injury. Therefore, this technique provides a new idea for the surgical treatment of aortic coarctations.
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http://dx.doi.org/10.1155/2020/3805385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245663PMC
March 2021

Endomyocardial fibrosis.

Cardiovasc Diagn Ther 2020 Apr;10(2):208-222

Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Background: Endomyocardial fibrosis (EMF) is a neglected cardiovascular disease of poverty which carries a poor prognosis with no specific treatment affecting mainly children and young adults. Here, we report our 10-year experience in the therapeutic management and surgical treatment for EMF.

Methods: From February 2009 to 2019 March, 55 patients diagnosed with EMF from our cardiology unit underwent surgical repair at our department's pediatric surgical division. There were 35 male, and 20 female patients whose ages varied from 1 year 2 months to 12 years mean age 5.7 (±3.2). We designed the study aimed at assessing the cardio-structural abnormalities and coronary vascular changes faced with EMF patients using echocardiography, and coronary angiography with a detailed and thorough surgical examination of each case.

Results: Of the 55 operated patients, 1 had mild lesions, 26 had moderate lesions, and 28 had severe heart disease. All but one patient was in NYHA functional class III or IV at the time of surgery. All but one female patient with mild ventricular lesions and no valvular involvement had severe atrioventricular valve regurgitation with valves considered suitable for both replacements; 45 patients mean age 6.0 (±3.1) and repair nine patients mean age 3.8 (±2.9). The mean endocardial thickness was 3,000 (±1519) µm.

Conclusions: The echocardiographic changes corresponded well to the findings on surgery and histopathology. The coronary changes seen included a spectrum of fibrin deposition, medial sclerosis and degeneration, and the formation of plexiform lesions. Surgically evaluating the resected cardiac tissue might help improve disease management.
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http://dx.doi.org/10.21037/cdt.2020.02.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225420PMC
April 2020

Pulmonary Arteriovenous Malformation Detected by Three-dimensional Computed Tomographic Angiography.

Heart Lung Circ 2017 Aug 22;26(8):e59-e61. Epub 2017 Mar 22.

Department of the Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China. Electronic address:

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http://dx.doi.org/10.1016/j.hlc.2017.02.016DOI Listing
August 2017

Congenital enlargement of the right atrium in a child with progressive dyspnea.

J Card Surg 2017 May 4;32(5):313-315. Epub 2017 Apr 4.

Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China.

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http://dx.doi.org/10.1111/jocs.13126DOI Listing
May 2017
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