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Given the overlapping functions listed above, members of our laboratory proposed that the AngIV/AT4 system closely interacts with the HGF/Met system [37,39,80,81]

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Remarkably, while recent studies have reported an association between low serum IGF-1 levels and all-cause mortality in hemodialysis patients, serum IGF-1 concentration was not useful as a predictor of cardiovascular events.120 In the vasculature, studies in animal models have shown that IGF-1 induces vasodilatory effects mediated by increasing nitric oxide synthesis in vascular endothelial cells.121,122 Moreover, in vitro studies with rat vascular smooth muscle cells have demonstrated that treatment with recombinant IGF-1 directly reduces the endogenous production of nitric oxide induced by exogeneous administration of interleukin-1β or TNF-α, suggesting a role of IGF-1 on the regulation of nitric oxide synthase at the sites of vascular injury.123 A list of preclinical and clinical studies on the actions of IGF-1 in cardiovascular diseases is shown in Table 4