Kyung-Sun Heo, Lan Phuong Phan, Nhi Thi Thao Le, Yujin Jin
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引用次数: 0
Abstract
Endothelial dysfunction plays a pivotal role in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, hypertension, heart failure, stroke, and peripheral artery disease. It disrupts vascular homeostasis, leading to reduced nitric oxide (NO) bioavailability, increased oxidative stress, and chronic inflammation, all of which collectively drive vascular damage, atherosclerotic plaque formation, and thrombosis. Additionally, shear stress-induced alterations in blood flow patterns, particularly disturbed flow (d-flow), aggravate endothelial dysfunction. Furthermore, the endothelial-to-mesenchymal transition (EndMT), a process in which endothelial cells acquire mesenchymal-like properties, contributes to vascular remodeling and accelerates CVD progression.
This review explores the significant role of epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs (ncRNAs), which serve as critical regulators of endothelial function in response to shear stress in endothelial dysfunction and the development of atherosclerosis. Furthermore, we discuss the pivotal role of endothelial dysfunction in cardiovascular and metabolic diseases, emphasizing the need for innovative therapeutic strategies beyond conventional treatments. In particular, we highlight the endothelial-protective mechanisms of emerging pharmacological agents, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, along with supporting clinical evidence demonstrating their efficacy in improving endothelial function and reducing cardiovascular risk.
期刊介绍:
Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.