Apolipoprotein CⅢ (apo-CⅢ) is a protein known since a long time and whose role in hyper triglyceridemia is well delineated.Apo-CⅢ is a 8.8 kDa glycoprotein secreted mostly by the liver and, to a lesser extent, by the intestine.Several functions have been proposed for the role of apo-CⅢ in the regulation of triglyceride-rich lipoproteins (TRLs)metabolism.Apo-CⅢ inhibits LPL activity, an enzyme that metabolizes triglycerides in TRLs, and facilitates their clearance from the circulation.Expression of apo-CⅢ is regulated by insulin via the IRE encoded in the APO-CⅢgene and insulin resistance may blunt the sensitivity to the normal insulin-mediated suppression of apo-CⅢ gene expression.Significant evidence links high APO-CⅢ to insulin resistance.Apo-CⅢ plasma level is elevated in centrally obese insulin-resistant individuals owing to overproduction of VLDL-apo-CⅢ.Lipoprotein metabolism disorders in visceral obesity have been attributed to insulin resistance and increased apo-CⅢ.In childhood and adolescence as well, apo-CⅢ increase is associated with insulin resistance and obesity.On clinical grounds, serum Apo-CⅢ levels are elevated in atherosclerosis, metabolic syndrome and diabetes mellitus, suggesting that Apo-CⅢ should be considered an independent risk factor for cardiovascular (CV) disease, but it was not evident whether the CV risk was due to the accompanying hypertriglyceridemia or to the apo-CⅢ molecule.Recently, it was proposed that apo-CⅢ per se has a significant role as a CV risk factor.Apo-CⅢ has been documented to affect several aspects of the endothelial cell function leading to endothelial dysfunction.Increased monocyte adhesion to EC, inhibition of insulin signaling, inhibition of eNOS and thus of nitric oxide are among the most relevant effects.On this ground, we evaluated serum Apo-CⅢ levels in obese fertile women without any other CV risk factor, compared to age-matched lean subjects to assess the Apo-CⅢ relationship with endothelial dysfunction (impaired endotheliumdependent vasodilatation EDV) and endothelial progenitor cells (EPC) number.In obese subjects, circulating EPC number and EDV were significantly decreased and plasma level of Apo-CⅢ was increased.In addition, it was strongly related to BMI and inversely related to EDV and circulating EPC number.Adjustment for age, BMI, EPC, all significantly correlated to EDV, had no effect on the association between ApoCⅢ and EDV.Our data suggest that Apo-CⅢ affects endothelial function in obesity and thus may represent one of the links between obesity and cardiovascular risk.