Endothelial Dysfunction as the Common Pathway Linking Obesity, Hypertension and Atherosclerosis

Endothelial dysfunction plays a central role in the pathogenesis of cardiovascular diseases, driven by a complex interplay of oxidative stress, metabolic imbalances, and adipokine dysregulation. Excessive reactive oxygen species reduce nitric oxide bioavailability by impairing endothelial nitric oxide synthase function, leading to vascular inflammation and impaired vasodilation. Adipose tissue-derived hormones such as leptin, adiponectin, and resistin exert opposing effects on vascular homeostasis, influencing inflammation and oxidative stress in obesity and metabolic syndrome. Dyslipidemia, particularly through oxidized LDL, initiates endothelial injury and foam cell formation, accelerating atherosclerosis. Furthermore, hypertension and obesity exacerbate vascular dysfunction by disrupting the balance between vasodilators and vasoconstrictors, enhancing oxidative stress, and altering perivascular adipose tissue function. These interrelated mechanisms contribute to the progression of atherosclerotic cardiovascular disease and diabetic vascular complications. A deeper understanding of these processes is essential for developing targeted interventions to restore endothelial health and reduce cardiometabolic risk.