Renin-angiotensin system and vasculature-focusing on insulin's action

摘要

Several recent clinical trials show that blocking agents of the renin-angiotensin system (RAS) reduces cardiovascular events in patients with metabolic syndrome based on insulin resistance Out laboratory has focused on the relationship between the vascular RAS and the action of insulin on the vasculature.We first revealed that addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases ang'iotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by blockade of the RAS by either an ACEI or an ARB suggesting a role for the RAS in insulin-mediated growth Insulin has a quite different effect in cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin state Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. This paper attempts to clarify the relationship between insulin resistance, the RAS and oxidative stress in vascular tissues to mimic in vivo conditions found in the metabolic syndrome.