Helman Tessa J, Headrick John P, Stapelberg Nicolas J C, Braidy Nady
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, NSW, Sydney, Australia.
School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia.
Front Cardiovasc Med. 2023 Apr 21;10:1072042. doi: 10.3389/fcvm.2023.1072042. eCollection 2023.
Stress is an important risk factor for modern chronic diseases, with distinct influences in males and females. The sex specificity of the mammalian stress response contributes to the sex-dependent development and impacts of coronary artery disease (CAD). Compared to men, women appear to have greater susceptibility to chronic forms of psychosocial stress, extending beyond an increased incidence of mood disorders to include a 2- to 4-fold higher risk of stress-dependent myocardial infarction in women, and up to 10-fold higher risk of Takotsubo syndrome-a stress-dependent coronary-myocardial disorder most prevalent in post-menopausal women. Sex differences arise at all levels of the stress response: from initial perception of stress to behavioural, cognitive, and affective responses and longer-term disease outcomes. These fundamental differences involve interactions between chromosomal and gonadal determinants, (mal)adaptive epigenetic modulation across the lifespan (particularly in early life), and the extrinsic influences of socio-cultural, economic, and environmental factors. Pre-clinical investigations of biological mechanisms support distinct early life programming and a heightened corticolimbic-noradrenaline-neuroinflammatory reactivity in females vs. males, among implicated determinants of the chronic stress response. Unravelling the intrinsic molecular, cellular and systems biological basis of these differences, and their interactions with external lifestyle/socio-cultural determinants, can guide preventative and therapeutic strategies to better target coronary heart disease in a tailored sex-specific manner.
压力是现代慢性疾病的一个重要风险因素，对男性和女性有不同影响。哺乳动物应激反应的性别特异性导致了冠状动脉疾病（CAD）的性别依赖性发展及其影响。与男性相比，女性似乎对慢性形式的心理社会压力更易感，这种易感性不仅表现为情绪障碍发病率增加，还包括女性应激依赖性心肌梗死风险高出2至4倍，以及应激性心肌病（一种在绝经后女性中最常见的应激依赖性冠状动脉 - 心肌疾病）风险高出多达10倍。应激反应的各个层面都存在性别差异：从对压力的初始感知到行为、认知和情感反应以及长期疾病结果。这些根本差异涉及染色体和性腺决定因素之间的相互作用、一生中（尤其是早年）的（不）适应性表观遗传调节以及社会文化、经济和环境因素的外在影响。生物学机制的临床前研究支持，在慢性应激反应的相关决定因素中，女性与男性相比存在独特的早期生命编程以及增强的皮质边缘 - 去甲肾上腺素 - 神经炎症反应性。揭示这些差异的内在分子、细胞和系统生物学基础，以及它们与外部生活方式/社会文化决定因素的相互作用，可以指导预防和治疗策略，以更有针对性的性别特异性方式更好地应对冠心病。
