Senescence marker protein 30 inhibits angiotensin II-induced cardiac hypertrophy and diastolic dysfunction.
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.
Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
Tomofumi
T
Misaka
Satoshi
S
Suzuki
Makiko
M
Miyata
Atsushi
A
Kobayashi
Akihito
A
Ishigami
Tetsuro
T
Shishido
Shu-ichi
S
Saitoh
Isao
I
Kubota
Yasuchika
Y
Takeishi
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D001794:Blood Pressure; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism*; D016922:Cellular Senescence; D003971:Diastole; D004452:Echocardiography; D005355:Fibrosis / Q000378:metabolism; D006973:Hypertension; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; D013481:Superoxides; D000804:Angiotensin II; D001205:Ascorbic Acid
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