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Biochem Biophys Res Commun. 2013 Sep 13;439(1):142-7. doi: 10.1016/j.bbrc.2013.08.002. Epub 2013 Aug 9.

Senescence marker protein 30 inhibits angiotensin II-induced cardiac hypertrophy and diastolic dysfunction.

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1
Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.

Abstract

BACKGROUND AND OBJECTIVE:

Senescence 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.

METHODS:

We 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).

RESULTS:

After 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.

CONCLUSIONS:

Cardiac-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.

KEYWORDS:

A; Aging; Angiotensin II; A′; BW; Cardiac remodeling; DHE; E; E′; FS; HW; IVS; LVEDD; LVESD; LVW; Oxidative stress; PW; SA-β-gal; SMP30; TL; Transgenic mouse; atrial mitral annular velocity; body weight; dihydroethidium; early diastolic mitral annular velocity; heart weight; intraventricular septal thickness; left ventricular end-diastolic dimension; left ventricular end-systolic dimension; left ventricular fractional shortening; left ventricular weight; peak atrial filling velocity; peak early diastolic left ventricular filling velocity; posterior wall thickness; senescence marker protein 30; senescence-associated β-galactosidase; tibial length

PMID:
23933320
DOI:
10.1016/j.bbrc.2013.08.002
[Indexed for MEDLINE]
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