Abstract 12520: Senescence Marker Protein-30 Deficiency Impairs Collateral Growth Under Ischemia in Aging
Aging causes collateral rarefaction, however underlying mechanism is unknown. Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate the SMP30’s effect on ischemia induced collateral growth, we examined the recovery of cutaneous blood flow (CBF) after femoral artery ligation by laser Doppler imaging in SMP30 knockout (KO) mice. Recoveries of CBF and tissue capillary density were suppressed in SMP30 KO mice compared to those of wild type mice. Acetylcholine (1 μM) induced nitric oxide (NO) generation, total thiol and reduced glutathione (GSH) levels in aorta of SMP30 KO mice were lower than those of wild type mice (NO; 2.6±4.5 vs. 86.2±9.2 nM, total thiol; 6.3±1.6 vs. 33.2±4.6 nmol/mg/protein, GSH; 5.1±0.8 vs. 18.6±2.1 nmol/mg/protein, P≤0.01, respectively). The levels of H2O2, NADPH oxidase activity measured by lucigenin-enhanced chemiluminescence, and asymmetric dimethylarginine (ADMA) were higher in aorta of SMP30 KO mice than those of wild type mice (H2O2; 21.2±3.2 vs. 3.4±0.8 pmol/mg/min, NADPH oxidase activity; 3240±254 vs. 982±106 RLU, ADMA; 6.4±0.8 vs. 2.4±0.4 nmol/mg protein, P≤0.01, respectively). Thus, SMP30 deficiency exacerbates oxidant stress related to NADPH oxidase activity enhancement and impairs eNOS activity, which leads to rarefaction of collateral growth induced by ischemia. These results suggest that oxidant stress and eNOS dysfunction play a key role in disrupting collateral growth in aging.
- © 2013 by American Heart Association, Inc.