Abstract 8880: Senescence Marker Protein 30 Inhibits Angiotensin II-induced Cardiac Remodeling
Backgrounds: Aging is a major risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30) is originally identified as an important aging marker protein, which the expression decreases androgen-independently with aging. SMP30 may act as an anti-aging factor in various organs, but the functional role of SMP30 in the heart has not been investigated.
Purpose: We tested the hypothesis that SMP30 functions as cardio-protective by anti-aging effects in angiotensin II (Ang II) -induced cardiac remodeling.
Methods and Results: SMP30 knockout mice (KO) and wild-type mice (WT) were subjected to continuous Ang II infusion (800 ng/kg/min). After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis were significantly higher in SMP30 KO mice than in WT mice (P<0.01, respectively). Echocardiography revealed that SMP30 KO mice had more severely impaired systolic and diastolic function with remarkably enlarged left ventricular dimension compared to WT mice (Table). Generation of reactive oxygen species related with activation of NADPH oxidase was greater in SMP30 KO mice than in WT mice (P<0.01). The numbers of TUNEL positive nuclei were markedly increased in SMP30 KO mice compared to WT mice (P<0.01). In addition, activation of signaling pathways leading to apoptosis such as increases in caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase were observed in SMP30 KO mice compared with WT mice (P<0.01, for each). The numbers of senescence-associated β-galactosidase-positive cardiomyocytes were increased via upregulation of p21 gene expression in SMP30 KO mice compared to WT mice (P<0.01).
Conclusions: This study demonstrates the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction and remodeling. These findings suggest that SMP30 has a cardio-protective role as anti-aging factor by anti-oxidative and anti-apoptotic effects in the heart.
- © 2011 by American Heart Association, Inc.