Abstract 162: Cardiac Overexpression of Senescence Marker Protein 30 Inhibits Angiotensin II-Induced Cardiac Hypertrophy and Remodeling
Backgrounds: Senescence marker protein 30 (SMP30) was originally identified as an important aging marker protein, and assumed to behave as an anti-aging factor. Previously, we demonstrated that deficiency of SMP30 exacerbates angiotensin II (Ang II)-induced reactive oxygen species (ROS) and cardiac adverse remodeling, suggesting that SMP30 may have a protective role in the heart. Thus, this study aimed to test the hypothesis that up-regulation of SMP30 inhibits cardiac hypertrophy and remodeling in response to Ang II.
Methods: We generated transgenic (SMP30-TG) mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. SMP30-TG mice and wild type littermate (WT) were subjected to continuous Ang II infusion (800 ng/kg/min).
Results: After 2 weeks, heart weight was significantly lower in SMP30-TG mice than in WT mice (P<0.01). Echocardiography revealed that calculated left ventricular mass and E/e’ were lower in SMP30-TG mice than in WT mice (P<0.01 and P<0.05, respectively), suggesting that diastolic function was preserved in SMP30-TG mice. Histological analysis showed that the degree of cardiac fibrosis was significantly decreased in SMP30-TG mice than in WT mice (P<0.05). Dihydroethidium staining demonstrated that generation of ROS was reduced in SMP30-TG mice compared with WT mice (P<0.05). Furthermore, the numbers of senescence-associated β-galactosidase-positive cardiomyocytes were decreased in SMP30-TG mice compared to WT mice (P<0.05). In addition, p21 mRNA level was significantly suppressed in SMP30-TG mice compared to WT mice (P<0.01).
Conclusions: This study demonstrated cardiac-specific overexpression of SMP30 inhibits Ang II-induced cardiac hypertrophy and remodeling. These findings suggested that SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects. Up-regulation of SMP30 might be a new strategy to approach senescent cardiac diseases and attenuate the development of heart failure particularly with hypertension.
- © 2012 by American Heart Association, Inc.