Angiotensin II type 1 receptor blockade attenuates in-stent restenosis by inhibiting inflammation and progenitor cells

The precise mechanism by which angiotensin 11 type I receptor blocker reduces in-stent restenosis in clinical trials is unclear. We, therefore, investigated the mechanism of in-stent neointima formation. Male cynomolgus monkeys and rabbits were fed a high-cholesterol diet and were allocated to untreated control and type I receptor blocker groups. Five days after grouping, multilink stents, were implanted in the iliac artery. The type I receptor blocker reduced the development of in-stent neointima formation by approximate to 30% in rabbits and monkeys. To investigate potential mechanisms, we examined the expression of renin-angiotensin system markers, all of which increased in monocytes and smooth muscle-like cells in the neointima and media within 7 days. The type I receptor blocker attenuated increased oxidative stress, the enhanced expression of markers of the rennin-angiotensin system and monocyte chemoattractant protein-1, and macrophage infiltration. The effects of type I receptor blocker on the differentiation of peripheral blood mononuclear cells into vascular progenitor cells were also examined. Treatment with type I receptor blocker suppressed the enhanced differentiation to smooth muscle progenitor cells induced by stenting. The type I receptor blocker attenuated in-stent neointima formation by inhibiting redox-sensitive inflammatory changes and by reducing recruitment of the progenitor cells. These potential actions of type I receptor blocker on inflammation and progenitor cells constitute a novel mechanism of suppression of in-stent restenosis by type I receptor blocker.