Publications by authors named "Zhi-Chong Chen"

6 Publications

  • Page 1 of 1

Klotho deficiency causes cardiac ageing by impairing autophagic and activating apoptotic activity.

Eur J Pharmacol 2021 Oct 9;911:174559. Epub 2021 Oct 9.

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

Objective: In this study, it was hypothesized that klotho deficiency plays an essential role in cardiac ageing in vivo and demonstrated that supplementation with exogenous klotho protects against cardiomyocyte ageing in vitro.

Methods: We measured the lifespan of wild-type (WT) and klotho-hypomorphic mutant (KL-/-) mice and recorded the cardiac function of the mice through echocardiography. We used immunofluorescence staining to detect the LC3B (microtubule-associated protein light chain 3 B), Beclin 1, Bax and Bcl 2 proteins. In vitro, H9c2 cells were incubated with different levels of D-galactose (D-gal) with or without klotho. SA-β-galactosidase staining and western blotting were performed to detect ageing-associated proteins (P53, P21 and P16), autophagy-associated proteins (LC3 II/LC3 I and Beclin 1) and apoptosis-associated proteins (Bax and Bcl 2). Moreover, one-step TUNEL apoptosis, CCK-8, cell morphology, Hoechst 33258 staining, lactate dehydrogenase (LDH) release, and caspase-3 activity assays were performed, and intracellular reactive oxygen species (ROS) levels were measured.

Results: Genetic klotho deficiency decreased lifespan and cardiac function in mice, impaired autophagic activity and increased apoptotic activity. Exogenous klotho attenuated cardiomyocyte ageing and reversed changes in autophagic and apoptotic activity caused by D-gal. Moreover, klotho supplementation prevented D-gal-induced oxidative stress and cytotoxicity.

Conclusions: Klotho might have a protective effect on cardiac ageing via autophagy activation and apoptosis inhibition.
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http://dx.doi.org/10.1016/j.ejphar.2021.174559DOI Listing
October 2021

Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Cardiac Structure and Function at Midlife: The CARDIA Study.

Front Cardiovasc Med 2021 16;8:687054. Epub 2021 Sep 16.

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

Glycemic variability was found associated with left ventricular structure and function in type 2 diabetes. But it is still unclear that whether the greater visit-to-visit fasting glucose (FG) variability in young adulthood among the community population is associated with cardiac function alteration and cardiac remodeling at midlife. The community-based prospective cohort study of Coronary Artery Risk in Young Adult (CARDIA) recruited young participants at the baseline age of 18-30 years during the period of 1985-1986 (Year 0). FG was measured at Year 0, 2, 10, 15, 20, and 25. The echocardiographic evaluation of cardiac structure and function was conducted at year 25. A total of 2,600 young adults mean (SD) aged at 24.9 years (3.6) of which 57.3% were women and 46.7% were African Americans had been included in the study. After multivariable adjusted, higher SD of mean FG (SD) is associated with lower early peak diastolic septal mitral annular velocity (e') (β [SE], -0.214 [0.080], < 0.01) and higher E/e' (β [SE], 0.307 [0.094], < 0.01), and higher coefficient of variation of the mean FG (CV) is also associated with lower e' (β [SE], -0.141[0.066], < 0.05) and higher E/e' (β [SE], 0.204 [0.078], < 0.01). The higher average real variation of mean FG (ARV) is associated with higher E/e' (β [SE], 0.178 [0.085], < 0.05) and higher left ventricular mass index (LVMI) (β [SE], 1.240 [0.618], < 0.05). The higher FG variability in young adulthood is associated with the subclinical change of left ventricular (LV) diastolic function at midlife.
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http://dx.doi.org/10.3389/fcvm.2021.687054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481606PMC
September 2021

NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging.

Aging (Albany NY) 2021 08 25;13(16):20534-20551. Epub 2021 Aug 25.

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

Objective: The NOD-like receptor protein 3 (NOD-like receptor protein 3, NLRP3) inflammasome is associated with many physiological processes related to aging. We investigated whether NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging dissected the underlying mechanism.

Methods: H9c2 cells were treated with different concentrations of D-galactose (D-gal, 0, 2, 10 and 50 g/L) for 24 hours. The cytochemical staining, flow cytometry and fluorescence microscope analysis were employed to detect the β-galactosidase (β-gal) activity. Western blot analysis was used to detect the age-associated proteins (P53, P21) and NLRP3 inflammasome proteins [NLRP3, apoptosis-associated speck-like protein (ASC)]. Confocal fluorescent images were applied to capture the colocalization of NLRP3 and caspase-1. Intracellular reactive oxygen species (ROS) was measured using 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) by flow cytometry and visualized using a fluorescence microscope. The IL-1β, IL-18 and lactate dehydrogenase (LDH) release were also detected.

Results: D-gal induced-H9c2 cells caused cardiocytes' aging changes (β-gal staining, CellEvent™ Senescence Green staining, P53, P21) in a concentration-dependent manner. NLRP3 inflammasomes were activated, IL-1β, IL-18 and LDH release and ROS generation were increased in the cardiocytes aging progress. When MCC950 inhibited NLRP3 inflammasomes, it attenuated the cardiocytes aging, yet the ROS generation was similar. Inhibition of ROS by NAC attenuated cardiocytes aging and inhibited the NLRP3 inflammasome activation at the same time. NLRP3 inflammasome activation by nigericin-induced cardiocytes cells aging progress.

Conclusions: NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging, and ROS generation may serve as a potential mechanism by which NLRP3 inflammasome is activated.
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http://dx.doi.org/10.18632/aging.203435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436929PMC
August 2021

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

Dehydroepiandrosterone attenuates pulmonary artery and right ventricular remodeling in a rat model of pulmonary hypertension due to left heart failure.

Life Sci 2019 Feb 31;219:82-89. Epub 2018 Dec 31.

Cardiovascular Department of the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address:

Aim: Pulmonary hypertension due to left heart failure (PH-LHF) is the most common cause of pulmonary hypertension. However, therapies for PH-LHF are lacking. Therefore, we investigated the effects and potential mechanism of dehydroepiandrosterone (DHEA) treatment in an experimental model of PH-LHF.

Main Method: PH-LHF was induced in rats via ascending aortic banding. The rats then received daily DHEA from Day 1 to Day 63 for the prevention protocol or from Day 49 to Day 63 for the reversal protocol. Other ascending aortic banding rats were left untreated to allow development of PH and right ventricular (RV) failure. Sham ascending aortic banding rats served as controls.

Key Finding: Significant increases in mean pulmonary arterial pressure (mPAP) and right ventricular end-diastolic diameter (RVEDD) were observed in the PH-LHF group. Therapy with DHEA prevented LHF-induced PH and RV failure by preserving mPAP and preventing RV hypertrophy and pulmonary artery remodeling. In preexisting severe PH, DHEA attenuated most lung and RV abnormalities. The beneficial effects of DHEA in PH-LHF seem to result from depression of the STAT3 signaling pathway in the lung.

Significant: DHEA not only prevents the development of PH-LHF and RV failure but also rescues severe preexisting PH-LHF.
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http://dx.doi.org/10.1016/j.lfs.2018.12.056DOI Listing
February 2019

The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease.

PLoS One 2016 7;11(7):e0157171. Epub 2016 Jul 7.

Department of Cardiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload.

Methods: Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group.

Results: Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group.

Conclusions: Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the proliferation and increasing the apoptosis of pulmonary arterial smooth muscle cells, and by attenuating the inflammation of pulmonary arteries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157171PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936674PMC
July 2017
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