Department of Cardiology, Pulmonology and Angiology Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Germany.
Free Radic Biol Med. 2021 Mar;165:265-281. doi: 10.1016/j.freeradbiomed.2021.01.040. Epub 2021 Jan 23.
Intact endothelial function plays a fundamental role for the maintenance of cardiovascular (CV) health. The endothelium is also involved in remote signaling pathway-mediated protection against ischemia/reperfusion (I/R) injury. However, the transfer of these protective signals into clinical practice has been hampered by the complex metabolic alterations frequently observed in the cardiometabolic continuum, which affect redox balance and inflammatory pathways. Despite recent advances in determining the distinct roles of hyperglycemia, insulin resistance (InR), hyperinsulinemia, and ultimately diabetes mellitus (DM), which define the cardiometabolic continuum, our understanding of how these conditions modulate endothelial signaling remains challenging. It is widely accepted that endothelial cells (ECs) undergo functional changes within the cardiometabolic continuum. Beyond vascular tone and platelet-endothelium interaction, endothelial dysfunction may have profound negative effects on outcome during I/R. In this review, we summarize the current knowledge of the influence of hyperglycemia, InR, hyperinsulinemia, and DM on endothelial function and redox balance, their influence on remote protective signaling pathways, and their impact on potential therapeutic strategies to optimize protective heterocellular signaling.
完整的内皮功能对于维持心血管（CV）健康起着至关重要的作用。内皮细胞还参与远程信号通路介导的缺血/再灌注（I/R）损伤保护。然而，这些保护信号在向临床实践的转化中受到了阻碍，因为在心脏代谢连续体中经常观察到复杂的代谢改变，这会影响氧化还原平衡和炎症途径。尽管最近在确定高血糖、胰岛素抵抗（InR）、高胰岛素血症以及最终的糖尿病（DM）在定义心脏代谢连续体中的独特作用方面取得了进展，但我们对这些情况如何调节内皮信号的理解仍然具有挑战性。人们普遍认为，内皮细胞（ECs）在心脏代谢连续体中会发生功能变化。除了血管张力和血小板-内皮细胞相互作用外，内皮功能障碍可能会对 I/R 期间的结果产生深远的负面影响。在这篇综述中，我们总结了高血糖、InR、高胰岛素血症和 DM 对内皮功能和氧化还原平衡的影响、它们对远程保护信号通路的影响，以及它们对优化保护性异细胞信号的潜在治疗策略的影响。
