Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.
Aging (Albany NY). 2024 May 13;16(9):7553-7577. doi: 10.18632/aging.205822.
After menopause, the incidence of cardiovascular disease rapidly rises in women. The disappearing protection provided by sex steroids is a consequence of the development of many risk factors. Preclinical studies are necessary to understand better the effects of ovarian hormones loss cardiac aging. To mimic menopause in mice and study its consequences, we delayed ovariectomy at 12 months and followed animals for 12 months. Using RNA sequencing, we investigated changes in the myocardial exome with aging. In addition, with four-core genotypes (FCG) transgenic mice, we studied sex chromosome effects on cardiac aging. Heart weight increased from 3 to 24 months (males + 35%, females + 29%). In males, 75% of this increase had occurred at 12 months; in females, only 30%. Gonadectomy of mice at 12 months blocked cardiac hypertrophy in both sexes during the second year of life. The dosage of the X chromosomes did not influence cardiac growth in young and older mice. We performed an RNA sequencing study in young and old mice. We identified new highly expressed genes modulated during aging (, , and ). The myocardial exome in older animals displayed few differences related to the animal's sex or the presence or absence of sex steroids for a year. We show that the morphological evolution of the heart depends on the biological sex via gonadal sex hormone actions. The myocardial exome of old male and female mice is relatively similar. Our study emphasizes the need to consider sex steroid effects in studying cardiac aging.
绝经后，女性心血管疾病的发病率迅速上升。性激素消失带来的保护作用是许多危险因素发展的结果。临床前研究对于更好地理解卵巢激素丧失对心脏衰老的影响是必要的。为了在小鼠中模拟绝经并研究其后果，我们将卵巢切除术延迟到 12 个月，并对动物进行了 12 个月的随访。我们使用 RNA 测序研究了随增龄心肌外显子组的变化。此外，我们利用四核心基因型（FCG）转基因小鼠研究了性染色体对心脏衰老的影响。从 3 个月到 24 个月，心脏重量增加（雄性增加 35%，雌性增加 29%）。在雄性中，这种增加的 75%发生在 12 个月时；在雌性中，只有 30%。在 12 个月时对小鼠进行性腺切除术，可阻止雌雄两性在生命第二年的心脏肥大。性染色体的剂量在年轻和年老的小鼠中都不影响心脏的生长。我们对年轻和年老的小鼠进行了 RNA 测序研究。我们鉴定了在衰老过程中表达上调的新基因（、和）。年老动物的心肌外显子组与动物的性别或存在或不存在性激素一年相关的差异很少。我们表明，心脏的形态演变取决于性腺性激素作用的生物学性别。年老的雄性和雌性小鼠的心肌外显子组比较相似。我们的研究强调了在研究心脏衰老时需要考虑到性激素的影响。
