Overexpression of myofibrillogenesis regulator-1 aggravates cardiac hypertrophy induced by angiotensin II in mice.
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 kappaB 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 kappaB 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 kappaB signaling pathway.
Li
Hong-Liang
HL
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
She
Zhi-Gang
ZG
Li
Tian-Bo
TB
Wang
Ai-Bing
AB
Yang
Qinglin
Q
Wei
Yu-Sheng
YS
Wang
Yi-Guang
YG
Liu
De-Pei
DP
D000804:Angiotensin II / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000139:chemically induced; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects*; D020257:Ventricular Remodeling / Q000502:physiology
D009124:Muscle Proteins; D016328:NF-kappa B; C495444:PNKD protein, human; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor