Systemic Endothelial Dysfunction as a Common Pathophysiological Axis of Cardiovascular, Renal, and Metabolic Disease: From Subclinical Damage to Progressive Organ Failure

Abstract

Endothelial dysfunction is a central pathophysiological mechanism driving the progression of cardiovascular, renal, and metabolic diseases by promoting inflammation, oxidative stress, thrombogenicity, and vascular homeostasis impairment. This narrative review aimed to examine the role of the endothelium as the unifying axis of the cardio-renal-metabolic continuum, describing its molecular mechanisms, clinical manifestations, early biomarkers, and current therapeutic implications. A structured literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, complemented by high-impact clinical guidelines and review articles. Current evidence indicates that reduced nitric oxide bioavailability, increased reactive oxygen species production, and activation of inflammatory pathways contribute to the concurrent development of atherosclerosis, chronic kidney disease, insulin resistance, and metabolic syndrome. In addition, biomarkers such as albuminuria and endothelial adhesion molecules enable the early identification of subclinical vascular injury. Recognizing endothelial dysfunction as a systemic process provides a comprehensive framework for prevention, risk stratification, and therapeutic strategies aimed at preserving vascular integrity and delaying progression to overt organ failure.