Sex-specific cardiac remodeling in aged rats after adolescent chronic stress: associations with endocrine and metabolic factors.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-08-23 DOI:10.1186/s13293-024-00639-7
Carley Dearing, Ella Sanford, Nicolette Olmstead, Rachel Morano, Lawson Wulsin, Brent Myers
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Abstract

Background: Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early-life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner.

Methods: Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43-62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups.

Results: Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased concentric VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity.

Conclusions: These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for assessing cardiovascular risk based on biological sex and prior adverse experiences.

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青春期慢性应激后老龄大鼠心脏重塑的性别特异性:与内分泌和代谢因素的关系
背景:心血管疾病是导致全球死亡的主要原因。心血管疾病的发病率因人而异,也因性别而异。虽然包括不良生活经历在内的多种因素会影响心血管疾病的发生和发展,但生理性别和压力史对老年心脏的潜在相互作用尚不清楚。为此,我们研究了性别和压力对衰老后左心室肥厚(VH)的影响。我们假设,生命早期的慢性压力暴露会影响行为和生理反应,从而以性别特异性的方式预测心脏重塑。方法:对在青春期晚期(出生后第 43-62 天)暴露于慢性可变压力的雄性和雌性大鼠的心脏进行组织学分析。这些动物在衰老至 15 个月之前接受了强迫游泳测试和葡萄糖耐量测试,并再次接受了挑战。然后利用预测分析分离出这些组别中与心脏重塑有关的因素:结果:早期慢性应激以性别特异性的方式影响心脏重塑。在有慢性应激史的大鼠中,雌性大鼠的同心VH增加。然而,在雌性大鼠组中,个体行为和生理参数与心脏重塑之间几乎没有关联。虽然雄性动物作为一个群体在慢性应激后没有VH,但它们表现出与心脏易感性的多种个体关联。年轻男性的被动应对和老年男性的主动应对与 VH 的关系取决于应激史。此外,基线皮质酮与未受压力男性的VH呈正相关,而长期受压力男性的VH与内脏脂肪率呈正相关:结论:这些结果表明,女性作为一个群体,特别容易受到早期生活压力对日后心脏重塑的影响。相反,男性在易感性方面的个体差异更大,心脏重塑的易感性与内分泌、代谢和行为措施有关,取决于压力史。这些结果最终支持了根据生理性别和先前的不良经历来评估心血管风险的框架。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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