Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy.
Int J Mol Sci. 2022 Apr 4;23(7):4009. doi: 10.3390/ijms23074009.
The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system.
医学界认识到与性别相关的生理差异和心血管疾病结局（CVD），最终导致心力衰竭。一般来说，绝经前女性的预后往往好于男性。解释为什么会这样并不简单。几十年来，雌激素（Es）等性激素已被确定为导致这些性别差异的主要因素之一。事实上，Es 似乎对女性具有保护作用，因为它们在绝经期间和绝经后下降，与 CV 风险增加和 HF 发展相一致。然而，临床试验表明，绝经后妇女的 E 替代治疗会导致不良心脏事件和乳腺癌风险增加。因此，需要更深入地了解与 E 相关的机制，为更好地预防和治疗女性 CVD 提供重要途径。值得注意的是，鞘脂（SLs）及其代谢与 E 活性密切相关。在 SLs 中，神经酰胺和鞘氨醇 1-磷酸在哺乳动物生理学中发挥着重要作用，特别是在心血管系统中，并且在男性和女性中的调节方式不同。根据这一观点，我们在这里探讨了关于 E 和 SL 代谢作用的最新实验和临床观察，强调了这些因素如何影响心血管系统。
