Sex- and age-related differences in renal and cardiac injury and senescence in stroke-prone spontaneously hypertensive rats

Biology of Sex Differences

Research

Aneesa Ansari¹  Sarah L. Walton¹  Kate M. Denton¹ 

[1]Department of Physiology, Monash University, Melbourne, VIC, Australia

[2]Cardiovascular Disease Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia

关键词: Cell senescence;    Kidney;    Heart;    Ageing;    Sex differences;    Stroke prone spontaneously hypertensive rats;   

DOI  :  10.1186/s13293-023-00519-6

 received in 2023-03-06, accepted in 2023-05-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSex differences play a critical role in the incidence and severity of cardiovascular diseases, whereby men are at a higher risk of developing cardiovascular disease compared to age-matched premenopausal women. Marked sex differences at the cellular and tissue level may contribute to susceptibility to cardiovascular disease and end-organ damage. In this study, we have performed an in-depth histological analysis of sex differences in hypertensive cardiac and renal injury in middle-aged stroke-prone spontaneously hypertensive rats (SHRSPs) to determine the interaction between age, sex and cell senescence.MethodsKidneys, hearts and urine samples were collected from 6.5- and 8-month-old (Mo) male and female SHRSPs. Urine samples were assayed for albumin and creatinine content. Kidneys and hearts were screened for a suite of cellular senescence markers (senescence-associated β-galactosidase, p16INK4a, p21, γH2AX). Renal and cardiac fibrosis was quantified using Masson’s trichrome staining, and glomerular hypertrophy and sclerosis were quantified using Periodic acid–Schiff staining.ResultsMarked renal and cardiac fibrosis, concomitant with albuminuria, were evident in all SHRSPs. These sequelae were differentially affected by age, sex and organ. That is, the level of fibrosis was greater in the kidney than the heart, males had greater levels of fibrosis than females in both the heart and kidney, and even a 6-week increase in age resulted in greater levels of kidney fibrosis in males. The differences in kidney fibrosis were reflected by elevated levels of cellular senescence in the kidney in males but not females. Senescent cell burden was significantly less in cardiac tissue compared to renal tissue and was not affected by age or sex.ConclusionsOur study demonstrates a clear sex pattern in age-related progression of renal and cardiac fibrosis and cellular senescence in SHRSP rats. A 6-week time frame was associated with increased indices of cardiac and renal fibrosis and cellular senescence in male SHRSPs. Female SHRSP rats were protected from renal and cardiac damage compared to age-matched males. Thus, the SHRSP is an ideal model to investigate the effects of sex and aging on organ injury over a short timeframe.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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