Vascular Biology Center and Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Department of Pharmacology, Tulane University, New Orleans, LA, USA.
Biol Sex Differ. 2024 Jun 6;15(1):46. doi: 10.1186/s13293-024-00624-0.
Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening.
We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics.
Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress-strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression.
Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.
性激素和性染色体在心血管疾病中起着至关重要的作用。睾丸激素在男性健康中起着关键作用。睾丸激素水平降低与心血管和心脏代谢疾病有关，包括炎症、动脉粥样硬化和 2 型糖尿病。睾丸激素替代对男性心血管健康有益或中性。睾丸激素缺乏与心血管事件有关。睾丸激素补充剂可改善低睾丸激素男性的性欲、增加肌肉力量和改善情绪。我们假设性染色体（XX 和 XY）与睾丸激素的相互作用在动脉僵硬中起作用。
我们使用了四种核心基因型雄性小鼠来了解性激素和性染色体组成在动脉僵硬中的固有贡献。年龄匹配的小鼠要么性腺完整，要么在八周时被阉割以清除内源性性激素，然后再进行八周。然后评估血压、脉搏波速度、超声心动图和离体被动血管力学。
动脉僵硬而不是血压在去势小鼠中比睾丸完整的小鼠更为显著，而与性染色体组成无关。去势小鼠的应激-应变曲线向左移位，颈动脉壁变薄。缺乏睾丸激素的性染色体组成（XX）增加了主动脉中的胶原蛋白沉积和 Kdm6a 基因表达。
睾丸激素剥夺增加了动脉僵硬和血管壁重塑。去势增加了 XX 性染色体组成的雄性小鼠中的 Col1α1。我们的研究表明，去势的 XX 性染色体组成的小鼠中主动脉收缩基因减少。
