Insulin resistance, hyperleptinemia and endothelial dysfunction in coronary restenosis

Impaired insulin sensitivity and endothelial dysfunction are important markers in the development of restenosis after coronary stenting. In addition, new markers of inflammation and endothelium activation, such as increased leptin levels, also have to considered. Many studies have shown that hyperinsulinemia and insulin resistance increase neointimal index measured six months after coronary stenting, and that insulin-sensitizers have beneficial effects by decreasing the rate of restenosis. The role of endothelial dysfunction in the process of restenosis is a fascinating problem. The pathobiology of restenosis in stented arteries is largely related to neointimal hyperplasia, which is dependent upon several factors, such as a reduction in nitric oxide activity that determines endothelial dysfunction and oxidative stress. Abnormal endothelium-dependent vasodilation (related to decreased nitric oxide production in the insulin-resistant state) might be explained by alterations in intracellular signaling and increased endothelin-1 production. Leptin is a hormone related to both fat metabolism and insulin resistance that has been recognized as an independent predictor of coronary restenosis. Chronic hyperleptinemia can reduce the synthesis of nitric oxide owing to the increased oxidative stress in endothelial cells. As a result, the goal in prevention of in-stent restenosis is to develop drugs that are able to act both as insulin- and endothelium-sensitizers.