Senescence marker protein 30 inhibits angiotensin II-induced cardiac hypertrophy and diastolic dysfunction |
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Authors: | Tomofumi Misaka Satoshi Suzuki Makiko Miyata Atsushi Kobayashi Akihito Ishigami Tetsuro Shishido Shu-ichi Saitoh Isao Kubota Yasuchika Takeishi |
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Affiliation: | 1. Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan;2. Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan;3. First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan |
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Abstract: | Background and objectiveSenescence marker protein 30 (SMP30) is assumed to behave as an anti-aging factor. Recently, we have demonstrated that deficiency of SMP30 exacerbates angiotensin II-induced cardiac hypertrophy, dysfunction and 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 adverse remodeling in response to angiotensin II.MethodsWe generated transgenic mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. Transgenic mice and wild-type littermate mice were subjected to continuous angiotensin II infusion (800 ng/kg/min).ResultsAfter 14 days, heart weight and left ventricular weight were lower in transgenic mice than in wild-type mice, although blood pressure was similarly elevated during angiotensin II infusion. Cardiac hypertrophy and diastolic dysfunction in response to angiotensin II were prevented in transgenic mice compared with wild-type mice. The degree of cardiac fibrosis by angiotensin II was lower in transgenic mice than in wild-type mice. Angiotensin II-induced generation of superoxide and subsequent cellular senescence were attenuated in transgenic mouse hearts compared with wild-type mice.ConclusionsCardiac-specific overexpression of SMP30 inhibited angiotensin II-induced cardiac adverse remodeling. SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects and could be a novel therapeutic target to prevent cardiac hypertrophy and remodeling due to hypertension. |
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Keywords: | SMP30, senescence marker protein 30 IVS, intraventricular septal thickness PW, posterior wall thickness LVEDD, left ventricular end-diastolic dimension LVESD, left ventricular end-systolic dimension FS, left ventricular fractional shortening E, peak early diastolic left ventricular filling velocity A, peak atrial filling velocity E&prime , early diastolic mitral annular velocity A&prime , atrial mitral annular velocity HW, heart weight LVW, left ventricular weight BW, body weight TL, tibial length DHE, dihydroethidium SA-β-gal, senescence-associated β-galactosidase |
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