Influence of pressure overload at different time on myocardial hypertrophy and mitophagy in SD rats
WANG Yue
XIE Yunbo
PEI Hanjun
SUN Shuyan
HUO Jingwei
GAO Yuan
HU Xuefeng
Abstract：Objective To explores the dynamic change law of myocardial mitophagy at different time points during pressure-overload-induced myocardial hypertrophy through establishing a pressure-overload-induced myocardial hypertrophy model.Methods SPF grade male SD rats were randomly divided into 5 groups,namely the 0-week(0W)group and the pressure-overload-induced myocardial hypertrophy groups at different time points(2-week[2W],4-week[4W],6-week[6W],and 8-week[8W]groups).A pressure-overload-induced myocardial hypertrophy model was established via abdominal aortic constriction surgery.The left ventricular structure was evaluated by directly measuring the left ventricular wall thickness,interventricular septum thickness and cardiac mass index,while Masson staining was performed to observe the degree of myocardial fibrosis.Western blotting assay was used to detect the expression of mitophagy-related proteins(LC3A/B,P62),myocardial hypertrophy-related proteins(BNP,β-MHC),apoptosis-related proteins(Bax,Bcl-2,Caspase-3,cleaved-Caspase-3,PDCD4),and mitochondrial oxidative stress-related protein SOD2 in myocardial tissue.The change patterns of these proteins were observed in each group at different time points.Results Compared with the 0W group,the 2W,4W,6W,and 8W groups showed significantly increased degrees of myocardial hypertrophy and fibrosis,elevated levels of cardiomyocyte apoptosis and mitochondrial oxidative stress,and a marked reduction in mitophagy.Under sustained pressure overload:The levels of myocardial apoptosis and mitochondrial oxidative stress exhibited a decreasing trend from 2W group to 6W group,followed by a significant increase in 8W group.In contrast,the level of mitophagy showed an increasing trend from 2W group to 6W group,and then a significant decrease at 8W group.Furthermore,the change in myocardial mitophagy was negatively correlated to the changes in myocardial apoptosis levels and mitochondrial oxidative stress levels.Conclusion Under sustained pressure overload,the myocardium exhibits significant hypertrophy,a continuous increase in the degree of fibrosis,a decrease in mitophagy levels,and a marked elevation(with fluctuating changes)in mitochondrial oxidative stress and myocardial apoptosis levels.These findings suggest that regulating mitophagy is a potential intervention target for improving myocardial hypertrophy,myocardial fibrosis,myocardial apoptosis and mitochondrial damage under long-term pressure overload.
Keywords：myocardial hypertrophyfibrosismyocardial apoptosismitochondrial oxidative stressmitophagy
Publication Date：2025-12-20
Online Publishing Date：2026-03-25(First online date of this platform, not the publication date of the document)
Pages：6( 1448-1453 )