Integrative Mechanisms of Osteoprotegerin in Cardiovascular Pathophysiology

Abstract

Osteoprotegerin (OPG), a glycoprotein in the tumor necrosis factor superfamily, regulates bone metabolism by suppressing the formation and activation of osteoclasts. Nonetheless, increasing evidence underscores its physiological importance, particularly in cardiovascular diseases (CVDs). Elevated OPG levels are associated with atherosclerosis, arterial calcification, and heart failure, thus indicating their involvement in cardiac remodeling and vascular pathology. OPG regulates calcification and vascular homeostasis by restricting the transdifferentiation of vascular smooth muscle cells into osteogenic phenotypes. OPG expression is aberrant in illnesses posing cardiovascular risk, such as aortic valve stenosis, chronic renal disease, and diabetes. Beyond structural regulation, OPG interacts with inflammatory and apoptotic mediators, including RANKL and TRAIL, in signaling pathways linking bone metabolism, inflammation, and vascular dysfunction. Myocardial infarction, left ventricular remodeling, and mortality are associated with elevated circulating OPG and altered OPG/TRAIL ratios. This review discusses molecular and clinical insights regarding OPG’s multifaceted role in CVDs, highlighting its potential as a regulator of disease etiology and a predictive biomarker. In cardiovascular medicine, understanding the OPG/RANKL/TRAIL axis has potential to facilitate targeted therapy and risk stratification.

Keywords

Osteoprotegerin / cardiovascular diseases / vascular calcification / RANKL / TRAIL / biomarker

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