Published online before print April 9, 2007, doi: 10.1161/HYPERTENSIONAHA.106.085399
(Hypertension. 2007;49:1399.)
© 2007 American Heart Association, Inc.
Original Articles |
Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in Mice
From the National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences (H.-L.L., Z.-G.S., A.-B.W., Y.-S.W., D.-P.L.) and Institute of Medicinal Biotechnology (T.-B.L., Y.-G.W.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; Joslin Diabetes Center and Department of Medicine (H.-L.L.), Harvard Medical School, Boston, Mass; and the Cardiovascular Research Institute (Q.Y.), Morehouse School of Medicine, Atlanta, Ga.
Correspondence to De-Pei Liu, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China. E-mail: liudp{at}pumc.edu.cn or Yi-Guang Wang, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China. E-mail wangyh456@yahoo.com.cn
Myofibrillogenesis regulator-1 (MR-1) augments cardiomyocytes hypertrophy induced by angiotensin II (Ang II) in vitro. However, its roles in cardiac hypertrophy in vivo remain unknown. Here, we investigate whether MR-1 can promote cardiac hypertrophy induced by Ang II in vivo and elucidate the molecular mechanisms of MR-1 on cardiac hypertrophy. We used a model of Ang II–induced cardiac hypertrophy by infusion of Ang II in female mice. In wild-type mice subjected to the Ang II infusion, cardiac hypertrophy developed after 2 weeks. In mice overexpressing human MR-1 (transgenic), however, cardiac hypertrophy was significantly greater than in wild-type mice as estimated by heart weight:body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our further results showed that cardiac inflammation and fibrosis observed in wild-type Ang II mice were augmented in transgenic Ang II mice. Importantly, increased nuclear factor 
B activation was significantly increased higher in transgenic mice compared with wild-type mice after 2 weeks of Ang II infusion. In vitro experiments also revealed that overexpression of MR-1 enhanced Ang II–induced nuclear factor B activation, whereas downregulation of MR-1 blocked it in cardiac myocytes. In conclusion, our results suggest that MR-1 plays an aggravative role in the development of cardiac hypertrophy via activation of the nuclear factor B signaling pathway.
Key Words: hypertrophy • myocardium • NF-B • myofibrillogenesis regulator-1 • fibrosis • angiotensin II
Related Article:
B Signaling, and Cardiac Remodeling
Hypertension 2007 49: 1225-1227.
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