心脏病的全球发病率正在增加,给医疗保健系统带来巨大的社会经济负担。心血管疾病的发病机制复杂,尚未完全了解,心脏的生理功能与调节良好的心肌运动密不可分。肌球蛋白轻链激酶(MLCK)是心肌收缩和舒张所必需的,心脏电生理稳态,血管神经收缩和血压调节。在这个意义上,MLCK似乎是心脏疾病的有吸引力的治疗靶标。MLCK通过多种途径参与心肌细胞运动和迁移,包括钙稳态的调节,肌球蛋白轻链磷酸化的激活,和刺激血管平滑肌细胞收缩或松弛。最近,肌球蛋白轻链的磷酸化已被证明与心肌运动信号的激活密切相关,MLCK通过肌球蛋白粗丝和肌动蛋白细丝的相互作用介导心脏的收缩和舒张功能。它通过维护细胞骨架的完整性起作用,改变肌球蛋白头部的构象,调节神经支配。MLCK控制血管收缩和舒张功能,并与肾上腺素能和交感神经系统的激活有关。细胞外运输,内皮通透性,以及一氧化氮和血管紧张素II的调节。此外,MLCK在心脏衰老过程中起着至关重要的作用。多种天然产物/植物化学物质和化合物,比如槲皮素,环孢菌素,和盐酸ML-7,已被证明可以调节心肌细胞MLCK。在设计新的治疗剂时应考虑这些化合物的MLCK修饰能力。这篇综述总结了MLCK在心血管系统中的作用机制,以及报道的化合物通过改变MLCK过程在心脏病中的治疗潜力。
The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. The pathogenesis of cardiovascular disease is complex and not fully understood, and the physiological function of the heart is inextricably linked to well-regulated cardiac muscle movement. Myosin light chain kinase (MLCK) is essential for myocardial contraction and diastole, cardiac electrophysiological homeostasis, vasoconstriction of vascular nerves and blood pressure regulation. In this sense, MLCK appears to be an attractive therapeutic target for cardiac diseases. MLCK participates in myocardial cell movement and migration through diverse pathways, including regulation of calcium homeostasis, activation of myosin light chain phosphorylation, and stimulation of vascular smooth muscle cell contraction or relaxation. Recently, phosphorylation of myosin light chains has been shown to be closely associated with the activation of myocardial exercise signaling, and MLCK mediates systolic and diastolic functions of the heart through the interaction of myosin thick filaments and actin thin filaments. It works by upholding the integrity of the cytoskeleton, modifying the conformation of the myosin head, and modulating innervation. MLCK governs vasoconstriction and diastolic function and is associated with the activation of adrenergic and sympathetic nervous systems, extracellular transport, endothelial permeability, and the regulation of nitric oxide and angiotensin II. Additionally, MLCK plays a crucial role in the process of cardiac aging. Multiple natural products/phytochemicals and chemical compounds, such as quercetin, cyclosporin, and ML-7 hydrochloride, have been shown to regulate cardiomyocyte MLCK. The MLCK-modifying capacity of these compounds should be considered in designing novel therapeutic agents. This review summarizes the mechanism of action of MLCK in the cardiovascular system and the therapeutic potential of reported chemical compounds in cardiac diseases by modifying MLCK processes.