背景:心血管疾病是全球死亡的主要原因。心血管疾病的发病率在寿命和性别之间都有所不同。虽然多重因素,包括不良的生活经历,影响心血管疾病的发展和进展,生物性别和应激史对老年心脏的潜在相互作用尚不清楚。为此,我们研究了性别和应激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,从而以性别特异性方式预测心脏重塑。
方法:对先前在青春期后期(出生后第43-62天)暴露于慢性可变应激的雄性和雌性大鼠的心脏进行组织学分析。这些动物在老化至15个月之前用强迫游泳测试和葡萄糖耐量测试进行攻击,并且再次受到攻击。然后使用预测分析来分离这些组中与心脏重塑相关的因素。
结果:生命早期慢性应激以性别特异性方式影响心脏重塑。在有慢性应激史的老鼠中,女性的同心VH增加。然而,在女性群体中,个体行为和生理参数与心脏重塑之间几乎没有关联.虽然男性作为一个群体在慢性压力后没有VH,他们表现出与心脏易感性的多个个体关联.年轻男性的被动应对和老年男性的主动应对以压力史依赖的方式与VH相关。此外,基线皮质酮与无应激男性的VH呈正相关,而慢性应激男性的VH与内脏肥胖呈正相关。
结论:这些结果表明,女性作为一个群体,特别容易受到生命早期压力对生命后期心脏重塑的影响。相反,男性在脆弱性上有更多的个体差异,心脏重塑的易感性与内分泌有关,新陈代谢,和行为措施取决于压力史。这些结果最终支持基于生物学性别和先前不良经历评估心血管风险的框架。
心血管疾病是全球死亡的主要原因。多种因素影响心血管疾病的发病率和严重程度,包括不良的生活经历,生物性别,和年龄。心脏结构的改变通过影响血液循环来预测负面的心血管健康;然而,压力史和生物性别对老年心脏的潜在相互作用尚不清楚。在这项研究中,我们研究了老化后慢性应激暴露对雄性和雌性大鼠心脏结构的影响.青春期的雄性和雌性大鼠长期受到压力,然后受到严格的挑战以检查行为,内分泌,慢性应激后和衰老后的代谢参数。量化心脏形态以检查行为和生理反应如何与心脏重塑相关。我们的研究结果表明,作为一个群体,先前暴露于慢性应激的雌性大鼠对心脏的内部重塑具有独特的敏感性。根据心室向内重塑的水平将受试者进一步分为亚组。虽然雄性大鼠对心脏结构没有表现出群体效应,男性心脏形态的个体变异性与应激史相关的内分泌和代谢参数。这里,与多个系统有相互作用,包括应对行为,压力荷尔蒙,和身体组成。此外,没有慢性应激史的男性在应激激素和心脏重塑程度之间存在相关性。然而,暴露于慢性压力的男性心脏结构与腹部脂肪之间存在相关性。总的来说,我们的研究结果表明,生物性别和应激史相互作用,以预测心血管易感性。
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.
Cardiovascular disease is the leading cause of death worldwide. Multiple factors influence the incidence and severity of cardiovascular disease including adverse life experiences, biological sex, and age. Alterations of heart structure predict negative cardiovascular health by impacting blood circulation; however, the potential interactions of stress history and biological sex on the aged heart are unknown. In this study, we examined how chronic stress exposure impacts heart structure in male and female rats after aging. Adolescent male and female rats were chronically stressed and then acutely challenged to examine behavioral, endocrine, and metabolic parameters both immediately following chronic stress and after aging. Heart morphology was quantified to examine how behavioral and physiological responses related to cardiac remodeling. Our results indicate that, as a group, female rats previously exposed to chronic stress were uniquely susceptible to inward remodeling of the heart. Subjects were further divided into sub-groups based on the level of inward remodeling of the ventricle. While male rats did not exhibit group effects on heart structure, individual variability in male heart morphology related to endocrine and metabolic parameters in a stress history-dependent manner. Here, there were interactions with multiple systems including coping behavior, stress hormones, and body composition. Moreover, males without a prior history of chronic stress had correlations between stress hormones and the degree of heart remodeling. However, males that were exposed to chronic stress had correlations between heart structure and abdominal fat. Overall, our results indicate that biological sex and stress history interact to predict cardiovascular susceptibility.