Changes in autophagy activity during left ventricular remodeling in spontaneously hypertensive rats
ZHAO Jian-qing
LONG Tao
YOU Jia-xiang
WANG Jin-ping
SHANG Yi-biao
YI Da-song
DING Lu
ZENG Jun-yi
Abstract：Objective To study the changes in autophagy activity during left ventricular remodeling in spontaneously hypertensive rats.Methods A total of 45 male spontaneously hypertensive rats(SHR)and 35 male Wistar Kyoto rats(WKY),which were four-week-old and specific-pathogen free,were randomly selected and fed in cages until 42 weeks.Systolic blood pressure was measured by tail-cuff method,and cardiac structure and function were detected by echocardiography at pre-set time points(6 weeks,8 weeks,12 weeks,18 weeks,24 weeks,32 weeks,42 weeks);At the same time points,heart specimens were dissected and left ventricular mass index(LVMI)was calculated,left ventricular remodeling was observed by histopathological staining,LC3 in left ventricular myocardium was detected by immunohistochemistry,and autophagosomes were detected by transmission electron microscopy.RT-qPCR was used to detect left ventricular remodeling and autophagy-related gene expression.Results With the increase of systolic blood pressure[6 weeks,(85.39±4.47)mmHg vs.42 weeks,(184.61±5.29)mmHg],the hypertrophy-related indexes of SHR:LVMI(8 weeks,2.58±0.17 vs.42 weeks,3.25±0.13),(IVST)interventricular septal thickness[6 weeks,(1.31±0.09)mm vs.42 weeks,(2.87±0.19)mm]and(LVPWT)left ventricular posterior wall thickness[6 weeks,(1.38±0.12)mm vs.42 weeks,(3.04±0.14)mm]gradually increased,indicating significant left ventricular hypertrophy;and(TDM)the left ventricular transverse diameter of myocardial[6 weeks,(16.0±0.20)μm vs.42 weeks,(30.7±1.90)μm]celland the expression of cardiac hypertrophy-related genes ANP and β-MHC increased first and then decreased with age.(CVF)The left ventricular Collagen Volume Fraction[6 weeks,(0.47±0.04)%vs.42 weeks,(2.43±0.24)%)]in SHR gradually increased with age,and the expression of myocardial fibrosis-related genes TGF-β1,collagen Ⅰ and collagen Ⅲ all first decreased and then increased.The expression of autophagy-related genes LC3 and Beclin-1 in left ventricular myocardium of SHR first increased and then decreased with age,while the expression of p62 first decreased and then increased.Meanwhile,immunohistochemistry showed that LC3 in left ventricular myocardium of SHR first increased and then decreased,and transmission electron microscopy showed that autophagy flux in left ventricular myocardium increased first and then decreased with age.Conclusions Autophagy is involved in left ventricular remodeling in spontaneously hypertensive rats,and autophagy activity changes dynamically from strong to weak with the development of left ventricular remodeling.
Keywords：AutophagySpontaneously hypertensive ratsLeft ventricular hypertrophy
Publication Date：2025-07-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 661-666 )