Publications by authors named "Xin-Xue Liao"

47 Publications

Causal effect of education on type 2 diabetes: A network Mendelian randomization study.

World J Diabetes 2021 Mar;12(3):261-277

Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.

Background: The causality between education and type 2 diabetes (T2DM) remains unclear.

Aim: To identify the causality between education and T2DM and the potential metabolic risk factors [coronary heart disease (CHD), total cholesterol, low-density lipoprotein, triglycerides (TG), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting insulin, fasting glucose, and glycated hemoglobin] from summarized genome-wide association study (GWAS) data used a network Mendelian randomization (MR).

Methods: Two-sample MR and network MR were performed to obtain the causality between education-T2DM, education-mediator, and mediator-T2DM. Summary statistics from the Social Science Genetic Association Consortium (discovery data) and Neale Lab consortium (replication data) were used for education and DIAGRAMplusMetabochip for T2DM.

Results: The odds ratio for T2DM was 0.392 (95%CI: 0.263-0.583) per standard deviation increase (3.6 years) in education by the inverse variance weighted method, without heterogeneity or horizontal pleiotropy. Education was genetically associated with CHD, TG, BMI, WC, and WHR in the discovery phase, yet only the results for CHD, BMI, and WC were replicated in the replication data. Moreover, BMI was genetically associated with T2DM.

Conclusion: Short education was found to be associated with an increased T2DM risk. BMI might serve as a potential mediator between them.
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http://dx.doi.org/10.4239/wjd.v12.i3.261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958473PMC
March 2021

Serum Albumin and Incident Heart Failure: Insights From Epidemiological and Mendelian Randomization Studies.

Circ Genom Precis Med 2020 12 15;13(6):e002989. Epub 2020 Nov 15.

Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University (X.-d.Z., S.-z.Z., H.-m.Z., X.-b.Z., X.-t.S., Z.-m.D., X.-x.L.).

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http://dx.doi.org/10.1161/CIRCGEN.120.002989DOI Listing
December 2020

Education and heart failure: New insights from the atherosclerosis risk in communities study and mendelian randomization study.

Int J Cardiol 2021 02 2;324:115-121. Epub 2020 Oct 2.

Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China; Guangdong Engineering Research Center for Light and Health, Guangzhou Higher Education Mega Center, Guangzhou, GuangDong, PR China. Electronic address:

Introduction: We aim to characterize the nature and magnitude of the prospective association between education and incident heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them.

Methods: The final sample size was 12,315 in this study. Baseline characteristics between education levels were compared using 1-way ANOVA test, the Kruskal-Wallis test, or the χ2 test. We used the Kaplan-Meier estimate to compute the cumulative incident of HF by education levels and the difference in estimate was compared using the log-rank test. Cox hazard regression models were used to explore the association between education levels and incident HF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies (GWASs) was used to estimate the causal influence of the education and incident HF.

Results: During a median follow-up of 25.1years, 2453 cases (19.9%) of incident HF occurred. After multiple adjustments in the final model, participants in the intermediate and advanced education levels were still associated with 18% and 21% decreased rate of incident HF separately. In MR analysis, we detected a protective causal association between education and HF (P=0.005).

Conclusions: Participants with higher education levels were associated with a decreased rate of incident HF. There was a causal association between education and HF.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.068DOI Listing
February 2021

Long-term tracking of fasting blood glucose variability and peripheral artery disease in people without diabetes.

BMJ Open Diabetes Res Care 2020 09;8(1)

Cardiology, Sun Yat-sen University First Affiliated Hospital, GuangZhou, China

Introduction: Long-term changes of fasting blood glucose (FBG) in relation to lower-extremity peripheral artery disease (lower-extremity PAD) in people without diabetes has barely been reported. Our study aimed to investigate the association between FBG variability and the incidence of lower-extremity PAD in people without diabetes.

Research Design And Methods: We included 7699 participants without prior lower-extremity PAD and diabetes from the Atherosclerosis Risk in Communities study in the final analysis. At least two measurements of FBG were required during follow-up. Variability of FBG was identified using SD, coefficient of variation (CV), variability independent of the mean (VIM) and average real variability. Lower-extremity PAD was defined as an ankle brachial index <0.9, or hospitalization with a lower-extremity PAD diagnosis. Cox regression model was used to calculate HR for incidence of lower-extremity PAD and FBG variability.

Results: During a median follow-up of 19.5 years, 504 (6.5 %) lower-extremity PAD events were observed, 54.4% (n=274) were male, and 17.5% (n=88) were African-American. FBG variability was positively associated with incident lower-extremity PAD, with a linear relationship. HRs for CV and VIM were 1.015 (95% CI: 1.001 to 1.03; p0.023), and 1.032 (95% CI: 1.004 to 1.06; p0.022) for lower-extremity PAD, respectively. Participants in the lowest quartile of CV were at lower lower-extremity PAD risk compared with the highest ones (HR: 1.499, 95% CI: 1.16 to 1.938; p0.002).

Conclusions: Higher FBG variability was independently associated with increased prevalence of lower-extremity PAD in people without diabetes.

Trial Registration Number: NCT00005131.
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http://dx.doi.org/10.1136/bmjdrc-2019-000896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526273PMC
September 2020

A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft.

Eur J Clin Invest 2021 Jan 25;51(1):e13405. Epub 2020 Sep 25.

Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice.

Methods And Results: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery.

Conclusions: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.
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http://dx.doi.org/10.1111/eci.13405DOI Listing
January 2021

Exploring the causal pathway from body mass index to coronary heart disease: a network Mendelian randomization study.

Ther Adv Chronic Dis 2020 27;11:2040622320909040. Epub 2020 May 27.

Cardiology Department, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, PR China.

Background: We applied a network Mendelian randomization (MR) framework to determine the causal association between body mass index (BMI) and coronary heart disease (CHD) and explored whether glycated hemoglobin (HbA1c) and lipid parameters (total cholesterol, TC; low-density lipoprotein cholesterol, LDL; high-density lipoprotein cholesterol, HDL; triglycerides, TG) serve as causal mediators from BMI to CHD by integrating summary-level genome-wide association study data.

Methods: Network MR analysis, an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed. Summary statistics from the GIANT consortium were used ( = 152,893) for BMI, CARDIoGRAMplusC4D consortium data were used ( = 184,305) for CHD, Global Lipids Genetics Consortium data were used ( = 108,363) for TC, LDL, HDL and TG, and MAGIC consortia data were used ( = 108,363) for HbA1c.

Results: The inverse-variance-weighted-method estimate indicated that the odds ratio (95% confidence interval) for CHD was 1.562 (1.391-1.753) per 1 standard deviation (kg/m) increase in BMI. Results were consistent in MR Egger method and weighted-median methods. MR estimate indicated that BMI was positively associated with HbA1c and TG, and negatively associated with HDL, but was not associated with TC or LDL. Moreover, HbA1c, TC, LDL, and TG were positively associated with CHD, yet there was no causal association between HDL and CHD. HbA1c was positively associated with TC, LDL, and HDL, but was not associated with TG.

Conclusions: Higher BMI conferred an increased risk of CHD, which was partially mediated by HbA1c and lipid parameters. HbA1c and TG might be the main mediators in the link from BMI to CHD.
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http://dx.doi.org/10.1177/2040622320909040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257848PMC
May 2020

Causal assessment of sleep on coronary heart disease.

Sleep Med 2020 03 30;67:232-236. Epub 2019 Aug 30.

The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Yue Xiu, GuangZhou, 510080, GuangDong, PR China. Electronic address:

Objective: Sleep is an essential physiological process that protects our physical and mental health. However, the causality of the association between sleep and coronary heart disease (CHD) is unknown. Mendelian randomization (MR), using genetic variants as instrumental variables to test for causality, can infer credible causal associations. We applied a two-sample MR framework to determine the causal association between sleep (sleeplessness, sleep duration, and daytime dozing) and CHD by integrating summary-level genome-wide association study (GWAS) data.

Methods: Data included in this study were the GWAS summary statistics datasets from the C4D Consortium for CHD; Neale Lab UKB-a:13 Consortium for sleeplessness; Neale Lab UKB-a:9 Consortium for sleep duration and Neale Lab UKB-a:15 Consortium for daytime dozing. The conventional MR approach (inverse variance weighted, IVW) method and Egger method were used. Heterogeneity was calculated using each of the different MR methods where possible. Horizontal pleiotropy was evaluated by p-value of the MR-Egger intercept.

Results: The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval, CI) for CHD was 3.924 (1.345-11.447) per standard deviation increase in sleeplessness (p = 0.012). Results were consistent in MR-Egger method (OR, 4.654; 95% CI, 1.191-18.186; p = 0.009). The genetically predicted sleeplessness was positively casually associated with CHD. The causal association between sleep duration (or daytime dozing) and CHD was not established.

Conclusion: Our analysis provided evidence supporting a causal relationship between sleeplessness (not sleep duration or daytime dozing) and CHD.
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http://dx.doi.org/10.1016/j.sleep.2019.08.014DOI Listing
March 2020

Serum albumin and atrial fibrillation: insights from epidemiological and mendelian randomization studies.

Eur J Epidemiol 2020 Feb 18;35(2):113-122. Epub 2019 Nov 18.

Cardiology Department, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Yue Xiu, Guangzhou, 510080, Guangdong, People's Republic of China.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Low serum albumin level is linked to the emergence of many cardiovascular diseases, including AF. In this study, we aim to characterize the nature and magnitude of the prospective association between serum albumin and incident AF in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. ARIC Study is a population-based, prospective, cohort study of cardiovascular risk factors in four US communities, initially consisting of 15,792 participants, aged 45-64 years, recruited between 1987 and 1989 (visit 1). The final sample size was 12,833 in this study. Baseline (visit 1) characteristics were compared between groups using one-way ANOVA test, Chi square test, or Kruskal-Wallis test as appropriate. We used multivariable Cox' hazard regression models to assess the association between albumin and incident AF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies was used to estimate the causal influence of the serum albumin and incident AF. During a median follow-up of 25.1 years, 2259 (17.6%) participants developed incident AF. After multiple adjustment, serum albumin was inversely associated with incidence of AF [HR = 0.90, 95% CI 0.86-0.94, per SD (0.27 g/dL) increase; HR = 0.80, 95% CI 0.71-0.91, Q4 vs. Q1]. In MR analysis, we detected no evidence for a causal relation between serum albumin level and AF in inverse-variance weighted (IVW) method (odds ratio: 0.996, 95% CI 0.980-1.012, per 1 g/dL increase of albumin; P = 0.620) without evidence of heterogeneity between estimates from individual SNPs (P = 0.981 [MR-Egger] and P = 0.860 [IVW]) nor pleiotropy effect (P = 0.193). The serum albumin level is independently inverse associated with incident AF in a linear pattern. However, MR analyses did not support a causal role of serum albumin in the etiology of AF.
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http://dx.doi.org/10.1007/s10654-019-00583-6DOI Listing
February 2020

Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study.

Nutr Metab Cardiovasc Dis 2020 02 16;30(2):233-240. Epub 2019 Sep 16.

The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Yue Xiu, Guangzhou, 510080, GuangDong, PR China. Electronic address:

Background And Aims: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data.

Methods And Results: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD.

Conclusions: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.
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http://dx.doi.org/10.1016/j.numecd.2019.09.013DOI Listing
February 2020

Phenomapping of subgroups in hypertensive patients using unsupervised data-driven cluster analysis: An exploratory study of the SPRINT trial.

Eur J Prev Cardiol 2019 11 18;26(16):1693-1706. Epub 2019 Jun 18.

Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, China.

Background: Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment.

Methods: An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters.

Results: Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55-0.98) and cluster 1 (HR 0.54, 95% CI 0.37-0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05-1.32).

Conclusion: Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.
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http://dx.doi.org/10.1177/2047487319856733DOI Listing
November 2019

Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials.

Cardiovasc Diabetol 2019 04 8;18(1):47. Epub 2019 Apr 8.

Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhong Shan 2nd Road, Guangzhou, 510080, China.

Background: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes.

Methods: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications.

Results: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant.

Conclusions: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.
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http://dx.doi.org/10.1186/s12933-019-0853-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454617PMC
April 2019

The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University.

Med Teach 2019 05 21;41(5):603-605. Epub 2018 Nov 21.

c Department of Pancreatobiliary Surgery , First Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.

To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.
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http://dx.doi.org/10.1080/0142159X.2018.1510177DOI Listing
May 2019

Comparative cardiovascular outcomes in the era of novel anti-diabetic agents: a comprehensive network meta-analysis of 166,371 participants from 170 randomized controlled trials.

Cardiovasc Diabetol 2018 06 5;17(1):79. Epub 2018 Jun 5.

Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents.

Methods: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included. We used network meta-analysis to obtain estimates for the outcomes of interests. In addition, post hoc correlation analysis of severe hypoglycemia and primary outcome as per ranking order was conducted. Outcomes were major adverse cardiovascular events (MACE) and all-cause mortality.

Results: A total of 170 trials (166,371 participants) were included. By class and by individual, sulfonylureas (SU) ranked last. Therefore, with SU as reference, categorically sodium-glucose co-transporter 2 inhibitor (SGLT2i), insulin (INS), glucagon-like peptide-1 receptor agonist, and dipeptidyl peptidase 4 inhibitor were significantly superior in term of MACE; as were SGLT2i and INS in term of all-cause mortality. Moreover, ranking orders of MACE and all-cause mortality were both positively correlated with that of severe hypoglycemia risk (by individual: R = 0.3178, P = 0.018; by class: R = 0.2574, P = 0.038).

Conclusions: Novel anti-diabetic agents possess favorable CV safety profile, despite small but robust differences between individuals. In addition, increase in CV risk was again shown to be partly attributable to a concomitant increase in the risk of severe hypoglycemia, for which SU performed the worst.
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http://dx.doi.org/10.1186/s12933-018-0722-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989345PMC
June 2018

Serum Klotho, vitamin D, and homocysteine in combination predict the outcomes of Chinese patients with multiple system atrophy.

CNS Neurosci Ther 2017 Aug 19;23(8):657-666. Epub 2017 Jun 19.

Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Aims: Neuroinflammation contributed to the pathogenesis of multiple system atrophy (MSA). We aimed to detect the correlation between inflammatory mediators, such as Klotho (Klt), vitamin D (25(OH)D) and homocysteine (Hcy), and disease severity among MSA patients.

Methods: A total of 53 MSA patients, 65 PD patients, and 62 normal subjects were recruited in our cross-sectional study. Serum Klotho (Klt), vitamin D (25(OH)D), and homocysteine (Hcy) levels were measured. Several scales were undertaken to assess the motor/nonmotor function and cognitive impairment of MSA.

Results: Decreased Serum Klt and 25(OH)D levels and increased Hcy levels were found in patients with MSA, compared with healthy controls. These results were more pronounced in male patients. The three biomarkers also displayed differences between MSA and PD subgroups based on genders. Interestingly, Klt, 25(OH)D and Hcy levels associated with cognition impairment, motor dysfunction, mood/cardiovascular disorder among MSA patients. In addition, the combination of Klt, 25(OH)D and Hcy had a better diagnostic ability for distinguishing MSA patients from healthy subjects, as well as distinguishing male MSA patients from male PD patients.

Conclusion: This study suggested that Klt, 25(OH)D and Hcy levels could be a potential predictor for MSA severity evaluation.
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http://dx.doi.org/10.1111/cns.12711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492708PMC
August 2017

A Nomogram to Predict Contrast Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention.

Int Heart J 2017 Apr 21;58(2):191-196. Epub 2017 Mar 21.

Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University.

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury (AKI). Emerging evidence has revealed that soluble klotho (sklotho) could be a novel biomarker for early AKI diagnosis. The aims of this study were to assess the predictive role of sklotho for CIN and to develop a prediction nomogram in patients undergoing percutaneous coronary intervention (PCI). This study is registered on Clinicaltrials.gov (NCT 02650336).Patients aged 18 years or older undergoing planned PCI were prospectively recruited between May 2014 and July 2015. CIN was defined as an increase in serum creatinine of 0.5 mg/dL within 48-72 hours after the procedure. Plasma sklotho was measured by enzyme linked immunosorbent assay (ELISA). Stratified analysis, interaction test, covariate screening, and curve fitting were performed to explore the association between sklotho and CIN. A nomogram was then developed and validated using the bootstrapped technique.A total of 192 patients aged 54.75 ± 12.19 years were selected, 32 (16.7%) of whom were diagnosed with CIN. A logistic regression model indicated significant associations between CIN and sklotho, age > 75 years, diabetes, and the Mehran risk score. Saturation effects analysis detected a two-stage change between sklotho and CIN, with the inflection point was 477.4 pg/mL. The area under the ROC curve was 0.758 and the sensitivity and specificity of this point were 90.6% and 53.9%, respectively. A nomogram was developed for the prediction of CIN and showed a bootstrapped-corrected area under the curve value of 0.913. In addition, sklotho significantly increased the predictive value of the nomogram.A strong association between sklotho and CIN was identified in patients undergoing elective PCI. A lower level of sklotho would be well correlated with CIN. The nomogram with sklotho is a useful tool to predict CIN in patients who will undergo PCI.
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http://dx.doi.org/10.1536/ihj.16-213DOI Listing
April 2017

Renin-angiotensin system inhibitors in patients with coronary artery disease who have undergone percutaneous coronary intervention.

Ther Adv Cardiovasc Dis 2016 Jun 15;10(3):172-7. Epub 2016 May 15.

Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, No. 58, ZhongShan Er Road, Guangzhou 510080, P. R. China

The percutaneous coronary intervention (PCI) procedure has become one of the pivotal options in the treatment of coronary artery disease (CAD). Although the PCI procedure has rapidly developed in China, some concerns including in-stent restenosis and dissatisfactory long-term prognosis remain unsolved. Large-scale randomized controlled clinical trials indicate that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) can reduce all-cause mortality and recurrent cardiac events in patients with CAD. ACEIs/ARBs are recommended as a fundamental treatment in the secondary prevention of CAD and reduce in-stent restenosis after PCI. This review focuses on the role of ACEIs/ARBs in improving long-term prognosis and reducing in-stent restenosis.
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http://dx.doi.org/10.1177/1753944716648851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933676PMC
June 2016

Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.

Drug Des Devel Ther 2016 5;10:129-39. Epub 2016 Jan 5.

Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice.
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http://dx.doi.org/10.2147/DDDT.S96315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708961PMC
October 2016

Effectiveness and Safety of Warfarin in Dialysis Patients With Atrial Fibrillation: A Meta-Analysis of Observational Studies.

Medicine (Baltimore) 2015 Dec;94(50):e2233

From the Department of Cardiology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

In routine practice, warfarin is widely used in dialysis patients with atrial fibrillation (AF) for stroke prevention though the ratio of risks to benefits remains unclear. Recent cohort studies investigating the association between warfarin use and the risks of stroke and bleeding in dialysis patients with AF present conflicting results. The objective of this study was to assess the effectiveness and safety of warfarin use in patients with AF undergoing dialysis. Three databases PubMed, EMBASE, and OVID were searched from their inception to August 2015. Observational studies which assessed the ischemic stroke or bleeding risk of warfarin use in dialysis patients with AF were included. Two reviewers independently extracted data and assessed methodological quality based on the Newcastle-Ottawa Scale score. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model and heterogeneity was assessed based on the Cochrane Q-statistic test and the I statistic. Metaregression analyses were performed to explore the source of heterogeneity. A total of 11 eligible studies with 25,407 patients were included in the analysis. Warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for ischemic stroke (HR 0.95, 95% CI 0.66-1.35). Sensitivity analyses found results to be robust. Metaregression analysis showed that demographic feature, clinical characteristics, or study-level variable had no impact of warfarin use on stroke risk. In addition, warfarin use was associated with a 27% higher risk for bleeding (95% CI 1.04-1.54). Overall, warfarin use did not have a significant association with reduced mortality (95% CI 0.96-1.11). It appears that warfarin use is not beneficial in reducing stroke risk, but with a high risk for bleeding in dialysis patients with AF. Randomized trials are needed to determine the risk-benefit ratio of warfarin in dialysis patients with AF.
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http://dx.doi.org/10.1097/MD.0000000000002233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058909PMC
December 2015

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk.

J Am Coll Cardiol 2015 Nov;66(20):2173-2184

Department of Cardiology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Background: Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events.

Objectives: This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.

Methods: We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.

Results: Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.

Conclusions: Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.
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http://dx.doi.org/10.1016/j.jacc.2015.09.029DOI Listing
November 2015

Critical appraisal of international guidelines on chronic heart failure: Can China AGREE?

Int J Cardiol 2016 Jan 20;203:111-4. Epub 2015 Oct 20.

Department of Cardiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2015.10.105DOI Listing
January 2016

Rationale and design of RETAIN study: Rosuvastatin Effect on Telomere-telomerase system in Acute coronary syndrome patients undergoing percutaneous coronary Intervention.

Int J Cardiol 2015 Apr 24;184:388-390. Epub 2015 Feb 24.

Department of cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2015.02.032DOI Listing
April 2015

Efficacy and safety of low-dose clopidogrel after 12-month dual antiplatelet therapy for patients having drug-eluting stent implantation.

J Thorac Dis 2014 May;6(5):459-65

1 Division of Cardiology, 2 Department of Ultrasound, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Background: To prevent stent thrombosis (ST) after implantation of drug-eluting stents (DESs) in patients with coronary heart disease, 12-month dual antiplatelet therapy (DAPT) is recommended. However, the optimal long-term antiplatelet regimen is not clear for the patients who have completed the 12-month DAPT.

Methods: We reviewed the data of 755 consecutive patients who had undergone percutaneous coronary intervention (PCI) three years ago and completed 12-month DAPT. They were divided into three groups according to the antiplatelet medication they had used for two years after 12-month DAPT [low-dose clopidogrel (Talcom(®), 25mg/d), clopidogrel (Plavix(®), 75mg/d) and aspirin (100 mg/d)]. The efficacy (a composite incidence of cardiac death, myocardial infarction and target vessel revascularization) and safety (incidences of bleeding, gastrointestinal trouble and drug discontinuation) were compared among the three groups.

Results: The rates of multi-vessel lesions, prior MI, hemoglobin A1C (HbA1c) and low-density lipoprotein cholesterol were significantly higher in the clopidogrel (75 mg/day) group than in the other two groups (P>0.05 for both comparisons). There was no significant difference in the overall composite incidence of cardiac death, myocardial infarction and target vessel revascularization in the three groups at three years after PCI. The rates of bleeding (especially minor bleeding), gastrointestinal trouble, drug discontinuation and any blood transfusion were markedly lower in the low-dose clopidogrel (25 mg/d) group than in the other two treatment groups (P<0.05).

Conclusions: The 25-mg maintenance dose of clopidogrel after 12-month DAPT may be more preferable to Chinese patients who have undergone DES implantation, because of its lower cost but no less efficacy and safety.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2014.02.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015003PMC
May 2014

Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via inhibition of leptin signaling in H9c2 cells.

Mol Cell Biochem 2014 Jun 1;391(1-2):147-55. Epub 2014 Apr 1.

Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.

Hydrogen sulfide (H₂S) protects cardiomyoblasts against high glucose (HG)-induced injury by inhibiting the activation of p38 mitogen-activated protein kinase (MAPK). This study aims to determine whether the leptin-p38 MAPK pathway is involved in HG-induced injury and whether exogenous H2S prevents the HG-induced insult through inhibition of the leptin-p38 MAPK pathway in H9c2 cells. H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. Cell viability; mitochondrial membrane potential (ΔΨ m); apoptosis; reactive oxygen species (ROS) level; and leptin, leptin receptor, and p38 MAPK expression level were measured by the methods indicated. The results showed pretreatment of H9c2 cells with NaHS before exposure to HG led to an increase in cell viability, decrease in apoptotic cells, ROS generation, and a loss of ΔΨ m. Exposure of H9c2 cells to 35 mM glucose for 24 h significantly upregulated the expression levels of leptin and leptin receptors. The increased expression levels of leptin and leptin receptors were markedly attenuated by pretreatment with 400 μM NaHS. In addition, the HG-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with 50 ng/ml leptin antagonist. In conclusion, the present study has demonstrated for the first time that the leptin-p38 MAPK pathway contributes to the HG-induced injury in H9c2 cells and that exogenous H₂S protects H9c2 cells against HG-induced injury at least in part by inhibiting the activation of leptin-p38 MAPK pathway.
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http://dx.doi.org/10.1007/s11010-014-1997-3DOI Listing
June 2014

PDE5 inhibitor sildenafil in the treatment of heart failure: a meta-analysis of randomized controlled trials.

Int J Cardiol 2014 Apr 24;172(3):581-7. Epub 2014 Jan 24.

Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China. Electronic address:

Background: Clinical trials have evaluated the use of phosphodiesterase (PDE) 5 inhibitors sildenafil as a potential adjunct in the treatment of heart failure (HF) with mixed results. Thus, we undertook a meta-analysis to evaluate the clinical viability of sildenafil in HF.

Methods: Relevant studies were searched and identified in the MEDLINE and EMBASE databases. Randomized clinical trials (RCT) comparing sildenafil to placebo, in heart failure patients, reporting at least one outcome of interest were included. Data were extracted regarding the characteristics and clinical outcomes.

Results: We identified 9 RCTs enrolling 612 HF patients. There were no significant differences in adverse events between sildenafil group and placebo group (RR=1.10, 95% CI=0.74 to 1.65, P=0.41), whereas sildenafil therapy was associated with a marked improvement in hemodynamic parameter peak VO2 (MD=3.25, 95% CI=2.07 to 4.42, P<0.00001) in HF with reduced ejection fraction (HFrEF) patients but not in HF with preserved ejection fraction (HFpEF) patients. Also, sildenafil therapy improved VO2 at anaerobic threshold (AT) (MD=3.47, 95% CI=1.68 to 5.27, P=0.0002), VE/VCO2 slope (MD=-7.06, 95% CI=-8.93 to -5.19, P<0.00001) and LV ejection fraction (MD=5.43, 95% CI=3.66 to 7.20, P<0.00001) compared to placebo in HF patients, which had no impact on blood pressure and heart rate. For quality of life (emotional function, fatigue and breathlessness), there was no significant difference between the two groups.

Conclusions: Sildenafil improved hemodynamic parameters particularly in HFrEF patients when compared to placebo, with no increase in adverse events. Sildenafil treatment was well tolerated and had no impact on quality of life.
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http://dx.doi.org/10.1016/j.ijcard.2014.01.102DOI Listing
April 2014

Higenamine Combined with [6]-Gingerol Suppresses Doxorubicin-Triggered Oxidative Stress and Apoptosis in Cardiomyocytes via Upregulation of PI3K/Akt Pathway.

Evid Based Complement Alternat Med 2013 5;2013:970490. Epub 2013 Jun 5.

Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road, Guangzhou 510080, China ; Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-Sen University, Guangzhou 510080, China.

Sini decoction is a well-known formula of traditional Chinese medicine, which has been used to treat cardiovascular disease for many years. Previously, we demonstrated that Sini decoction prevented doxorubicin-induced heart failure in vivo. However, its active components are still unclear. Thus, we investigated the active components of Sini decoction and their cardioprotective mechanisms in the in vitro neonatal rat cardiomyocytes and H9c2 cell line models of doxorubicin-induced cytotoxicity. Our results demonstrated that treatment with higenamine or [6]-gingerol increased viability of doxorubicine-injured cardiomyocytes. Moreover, combined use of higenamine and [6]-gingerol exerted more profound protective effects than either drug as a single agent, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. In addition, we found that treatment with doxorubicin reduced SOD activity, increased ROS generation, enhanced MDA formation, induced release of LDH, and triggered the intrinsic mitochondria-dependent apoptotic pathway in cardiomyocytes, which was inhibited by cotreatment of higenamine and [6]-gingerol. Most importantly, the cytoprotection of higenamine plus [6]-gingerol could be abrogated by LY294002, a PI3K inhibitor. In conclusion, combination of higenamine and [6]-gingerol exerts cardioprotective effect against doxorubicin-induced cardiotoxicity through activating the PI3K/Akt signaling pathway. Higenamine and [6]-gingerol may be the active components of Sini decoction.
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http://dx.doi.org/10.1155/2013/970490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687593PMC
July 2013

Spinal MCP-1 contributes to the development of morphine antinociceptive tolerance in rats.

Am J Med Sci 2012 Dec;344(6):473-9

Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China.

Background: The chemokine monocyte chemoattractant protein-1 (MCP-1) has been shown to contribute to neuropathic pain. However, whether MCP-1 is involved in the development of morphine antinociceptive tolerance is incompletely understood.

Methods: Morphine antinociceptive tolerance was induced by intrathecal administration of 15 μg of morphine daily for 7 days. Immunohistochemistry was used to test the changes in the morphology of spinal MCP-1 immunoreactivity and OX-42-IR. The role of MCP-1 in morphine antinociceptive tolerance is explored by hot-water tail-flick test.

Results: Our findings showed that intrathecal chronic morphine exposure obviously increased MCP-1 immunoreactivity in the spinal cord. Moreover, the increased MCP-1 immunoreactivity was observed mainly in the spinal neurons. Intrathecal injections of MCP-1-neutralizing antibody significantly reduced the development of morphine antinociceptive tolerance, suggesting that spinal neuronal MCP-1 contributes to tolerance to morphine antinociception. Treatment with MCP-1-neutralizing antibody also reduced the spinal microglial activation induced by chronic morphine treatment.

Conclusions: This study revealed for the first time that spinal neuronal MCP-1 is a key mediator of the spinal microglial activation and that spinal MCP-1 is involved in morphine antinociceptive tolerance. Inhibition of MCP-1 may provide a new therapy for morphine tolerance management.
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http://dx.doi.org/10.1097/MAJ.0b013e31826a82ceDOI Listing
December 2012

Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress.

Mol Cell Biochem 2012 Apr 28;363(1-2):419-26. Epub 2011 Dec 28.

Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

The roles of hydrogen sulfide (H(2)S) and endoplasmic reticulum (ER) stress in doxorubicin (DOX)-induced cardiotoxicity are still unclear. This study aimed to dissect the hypothesis that H(2)S could protect H9c2 cells against DOX-induced cardiotoxicity by inhibiting ER stress. Our results showed that exposure of H9c2 cells to DOX significantly inhibited the expression and activity of cystathionine-γ-lyase (CSE), a synthetase of H(2)S, accompanied by the decreased cell viability and the increased reactive oxygen species (ROS) accumulation. In addition, exposure of cells to H(2)O(2) (an exogenous ROS) mimicked the inhibitory effect of DOX on the expression and activity of CSE. Pretreatment with N-acetyl-L: -cysteine (NAC) (a ROS scavenger) attenuated intracellular ROS accumulation, cytotoxicity, and the inhibition of expression and activity of CSE induced by DOX. Notably, the ER stress-related proteins, including glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were obviously upregulated in DOX-treated H9c2 cells. Pretreatment with sodium hydrosulfide (NaHS, a H(2)S donor) before DOX exposure markedly suppressed DOX-induced overexpressions of GRP78 and CHOP, cytotoxicity and oxidative stress. In conclusion, we have demonstrated that ROS-mediated inhibition of CSE is involved in DOX-induced cytotoxicity in H9c2 cells, and that exogenous H(2)S can confer protection against DOX-induced cardiotoxicity partly through inhibition of ER stress.
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http://dx.doi.org/10.1007/s11010-011-1194-6DOI Listing
April 2012

Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells.

Mol Cell Biochem 2012 Mar 2;362(1-2):149-57. Epub 2011 Dec 2.

Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Hydrogen sulfide (H(2)S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H(2)S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl(2)), a chemical hypoxia mimetic agent, was applied to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury model. The results showed that pretreatment with NaHS (a donor of H(2)S) before exposure to CoCl(2) attenuated the decreased cell viability, the increased apoptosis rate, the loss of mitochondrial membrane potential (ΔΨm), and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells. Exposure of H9c2 cells to CoCl(2) or hydrogen peroxide (H(2)O(2)) upregulated expression of phosphorylated (p) ERK1/2, which was reduced by pretreatment with NaHS or N-acetyl-L-cysteine, a ROS scavenger. More importantly, U0126, a selective inhibitor of ERK1/2, mimicked the above cytoprotection of H(2)S against CoCl(2)-induced injury in H9c2 cells. In conclusion, these results indicate that H(2)S protects H9c2 cells against chemical hypoxia-induced injury partially by inhibiting ROS-mediated activation of ERK1/2.
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http://dx.doi.org/10.1007/s11010-011-1137-2DOI Listing
March 2012

Regular exercise-induced increased number and activity of circulating endothelial progenitor cells attenuates age-related decline in arterial elasticity in healthy men.

Int J Cardiol 2013 May 28;165(2):247-54. Epub 2011 Sep 28.

Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

Background: Deficiency in number and activity of circulating EPCs is associated with reduced arterial elasticity in humans with advancing aging. Physical exercise can increase the number and activity of circulating EPCs in humans. Here we investigated whether regular exercise-induced enhanced circulating endothelial progenitor cells (EPCs) improves age-related decline in arterial elasticity in healthy men.

Methods: In a cross-sectional study, the number and activity of circulating EPCs as well as brachial-ankle pulse wave velocity (baPWV) of young and older sedentary or endurance-trained healthy men were studied. Then we observed the effect of regular exercise on circulating EPCs and baPWV of 10 older and 10 young sedentary healthy men.

Results: In both sedentary and endurance-trained men, the number and activity of circulating EPCs were significantly low in older men compared with young men, which was paralleled to increased baPWV. After three months of regular exercise, the number and activity of circulating EPCs increased, and the baPWV of 10 older and 10 young sedentary healthy men decreased. However, the increased number and activity of circulating EPCs and decreased baPWV of older sedentary healthy men were higher. There was a close correlation between circulating EPCs and baPWV. Multivariate analysis identified proliferative activity of circulating EPCs as an independent predictor of baPWV.

Conclusions: The present study demonstrates for the first time that regular physical exercise-induced enhanced circulating EPCs attenuates age-related decline in arterial elasticity in healthy men. These findings provide novel insights into the protective effects of exercise on age-related vascular injury.
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http://dx.doi.org/10.1016/j.ijcard.2011.08.055DOI Listing
May 2013

Soluble Nogo-66 receptor prevents synaptic dysfunction and rescues retinal ganglion cell loss in chronic glaucoma.

Invest Ophthalmol Vis Sci 2011 Oct 28;52(11):8374-80. Epub 2011 Oct 28.

Otorhinolaryngology Hospital, Guangzhou,Guangdong, China.

Purpose: Myelin inhibitory proteins inhibit axon growth and synaptic function by binding to the Nogo-66 receptor (NgR)1 in the central nervous system. Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. Synaptic degeneration is thought to be an early pathology of neurodegeneration in glaucoma and precedes RGC loss. The authors aimed to examine whether the NgR1 antagonist promotes synaptic recovery and RGC survival in glaucoma.

Methods: Experimental ocular hypertension model was induced in adult rats with laser coagulation of the episcleral and limbal veins. NgR1 antagonist, soluble NgR1 (sNgR-Fc) was administrated to examine their effect on synaptic recovery and RGC survival. Expression of c-Fos, a neuronal connectivity marker, in the retinas was investigated using immunohistochemistry.

Results: NgR1 was expressed in RGCs and upregulated after intraocular pressure elevation. Treatment with sNgR-Fc significantly reduced RGC loss at 2 and 4 weeks after the induction of ocular hypertension and also promoted RGC survival after optic nerve transection. There was no RGC loss at 5 days but there was significant synaptic degeneration as measured by c-Fos. Administration of sNgR-Fc attenuated synaptic degeneration at 5 days, and at 2 and 4 weeks.

Conclusions: These data suggest that synaptic degeneration may be an initial molecular mechanism for neurodegeneration in glaucoma and appropriate NgR1 antagonism may delay the progression of the disease.
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http://dx.doi.org/10.1167/iovs.11-7667DOI Listing
October 2011
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