Abstract 11394: Decrease of Senescence Marker Protein-30 in Aging Impairs Collateral Growth Under Ischemia

Abstract

Aging decreases collateral-dependent flow recovery following ischemic arterial obstruction. However, the critical management has been lacked in clinical setting. Senescence marker protein-30 (SMP30) is a novel aging marker, which is assumed to act as an anti-aging factor in various organs. Therefore, we studied the effect of SMP30 on ischemia-induced collateral growth in C57BL/6 mice with young [8 weeks old (W)] and old (92 W), and SMP30 knockout (KO) mice (8 W). The SMP30 expression in gastrocnemius tissue was decreased in old mice compared to that of young mice. The recoveries of cutaneous blood flow in hindlimb after femoral artery ligation and tissue capillary density were suppressed in old and SMP30 KO mice compared to those in young mice. Nitric oxide generation induced by L-arginine was lower in old and SMP30 KO mice than that in young mice. The levels of NADPH oxidase activity and superoxide production in the ischemic tissue were higher in old and SMP30 KO mice than in young mice. The phosphorylated eNOS and Akt levels and VEGF levels in ischemic muscle were lower in old and SMP30 KO mice than in young mice (VEGF: Old mice 266±32, SMP30 KO 238±34, Young 414±48 pg/mg, P<0.01 ). Decrease of SMP30 exacerbates oxidative stress related to NADPH oxidase activity enhancement and impairs Akt-eNOS pathway, which leads to rarefaction of vasculogenesis induced by ischemia. These results suggest that SMP30 plays a key role in disrupting collateral growth under ischemia in aging.