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To review studies of vascular endothelial dysfunction in obesity, discuss potential mechanisms of disease, and address the therapeutic effects of weight loss interventions on arterial health.Endothelial dysfunction represents the earliest abnormality in the development of vascular disease, and is pathophysiologically linked to subsequent atherosclerosis progression and cardiovascular disease events. Obesity is closely associated with a number of established cardiovascular risk factors, including diabetes mellitus, insulin resistance, dyslipidemia, and hypertension that are cumulatively damaging to the endothelium. In addition, there is now a growing recognition of non-traditional risk factors as potential modulators of the endothelial phenotype in obesity, including fat tissue production of proatherogenic adipokines, oxidative stress, and chronic inflammation. Clinical studies have demonstrated that even modest weight loss reverses endothelial dysfunction, and the restoration of arterial homeostasis could potentially reduce cardiovascular risk.Obesity is associated with altered arterial homeostasis and endothelial dysfunction. Mechanisms of disease are related to a complex interplay of metabolic and inflammatory factors that coordinately improve along with arterial function in response to weight loss interventions.