Kant Shawn, Feng Jun
Cardiothoracic Surgery Research Laboratory, Department of Medicine, Rhode Island Hospital, Brown University Health, Providence, RI, United States.
Department of Surgery, Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
Front Cardiovasc Med. 2025 Aug 25;12:1618343. doi: 10.3389/fcvm.2025.1618343. eCollection 2025.
Protein kinases have crucial roles in intracellular signal transduction pathways that affect a wide range of biochemical processes, including apoptosis, metabolism, proliferation, and protein synthesis. Vascular endothelial cells are important regulators of vasomotor tone, tissue/organ perfusion, and inflammation. Since its discovery in the late 1970s, a growing body of literature implicates protein kinase C (PKC) in pathways involving angiogenesis, endothelial permeability, microvascular tone, and endothelial activation. Hence the objective of this review, to characterize the role of PKC in vascular endothelial cells. After discussing the basic principles of PKC structure and function, the focus shifts to abnormal PKC activity driving endothelial dysfunction in three major pathologies whose hallmark is significant vascular disease: diabetes mellitus, hypoxia/ischemia-reperfusion injury, and hypertension. Themes addressed include endothelial cell cycle derangement, endothelial oxidative stress, endothelial activation/inflammation, and impaired endothelial barrier integrity. Achieving a comprehensive understanding of endothelial cell-PKC pathophysiology may lead to development of new therapeutic targets for mitigating morbidity and mortality in these disease states.
蛋白激酶在细胞内信号转导途径中发挥着关键作用，这些途径影响广泛的生化过程，包括细胞凋亡、代谢、增殖和蛋白质合成。血管内皮细胞是血管舒缩张力、组织/器官灌注和炎症的重要调节因子。自20世纪70年代末被发现以来，越来越多的文献表明蛋白激酶C（PKC）参与了涉及血管生成、内皮通透性、微血管张力和内皮激活的途径。因此，本综述的目的是阐述PKC在血管内皮细胞中的作用。在讨论了PKC结构和功能的基本原理后，重点转向在三种以严重血管疾病为特征的主要病理状态下，异常的PKC活性导致内皮功能障碍：糖尿病、缺氧/缺血-再灌注损伤和高血压。涉及的主题包括内皮细胞周期紊乱、内皮氧化应激、内皮激活/炎症以及内皮屏障完整性受损。全面了解内皮细胞-PKC病理生理学可能会为减轻这些疾病状态下的发病率和死亡率开发新的治疗靶点。
