Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-06-06 DOI:10.1186/s13293-024-00624-0
Anil Sakamuri, Bruna Visniauskas, Isabella Kilanowski-Doroh, Alexandra B McNally, Ariane Imulinde, Anne Kamau, Divya Sengottaian, John McLachlan, Montserrat Anguera, Franck Mauvais-Jarvis, Sarah H Lindsey, Benard O Ogola
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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睾酮缺乏会促进动脉僵化,与性染色体互补无关。
背景:性激素和性染色体在心血管疾病中起着至关重要的作用。睾酮对男性健康起着至关重要的作用。睾酮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。睾酮替代对男性心血管健康有益或无益。睾酮缺乏与心血管事件有关。性腺功能低下的男性补充睾酮可提高性欲、增强肌肉力量并改善情绪。我们假设性染色体(XX 和 XY)与睾酮的相互作用在动脉僵化中发挥作用:我们使用四种核心基因型雄性小鼠来了解性激素和性染色体互补在动脉僵化中的内在作用。年龄匹配的小鼠要么性腺完好无损,要么在八周时被阉割,再经过八周清除内源性性激素。随后对血压、脉搏波速度、超声心动图和体内外被动血管力学进行评估:结果:与性染色体互补无关,阉割小鼠的动脉僵化比睾丸未受损的小鼠更明显,但血压却不明显。阉割小鼠的应力-应变曲线左移,颈动脉壁变薄。在没有睾酮的情况下,性染色体互补(XX)增加了主动脉中胶原蛋白的沉积和Kdm6a基因的表达:结论:睾酮剥夺会增加动脉僵化和血管壁重塑。阉割会增加具有 XX 性染色体互补的雄性小鼠的 Col1α1。我们的研究显示,性染色体为 XX 的阉割小鼠的主动脉收缩基因比 XY 小鼠减少。
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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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