Role of myofibrillogenesis regulator-1 in myocardial hypertrophy.
Myofibrillogenesis regulator-1 (MR-1) is a novel homologous gene, identified from a human skeletal muscle cDNA library, that interacts with contractile proteins and exists in human myocardial myofibrils. The present study investigated MR-1 protein expression in hypertrophied myocardium and MR-1 involvement in cardiac hypertrophy. Cardiac hypertrophy was induced by abdominal aortic stenosis (AAS) in Sprague-Dawley rats. Left ventricular (LV) hypertrophy was assessed by the ratio of LV wet weight to whole heart weight (LV/HW) or LV weight to body weight (LV/BW). Rat MR-1 (rMR-1) expression in the myocardium was detected by immunohistochemical and Western blotting analysis. Hypertrophy was induced by ANG II incubation in cultured neonatal rat cardiomyocytes. The effect of rMR-1 RNA interference on ANG II-induced hypertrophy was studied by transfection of cardiomyocytes with an RNA interference plasmid, pSi-1, which targets rMR-1. Hypertrophy in cardiomyocytes was assessed by [3H]Leu incorporation and myocyte size. rMR-1 protein expression in cardiomyocytes was detected by Western blotting. We found that AAS resulted in a significant increase in LV/HW and LV/BW: 89% and 86%, respectively (P < 0.01). Immunohistochemistry and Western blot analysis demonstrated upregulated rMR-1 protein expression in hypertrophic myocardium. ANG II induced a 24% increase in [3H]Leu incorporation and a 65.8% increase in cell size compared with control cardiomyocytes (P < 0.01), which was prevented by treatment with losartan, an angiotensin (AT1) receptor inhibitor, or transfection with pSi-1. rMR-1 expression increased in ANG II-induced hypertrophied cardiomyocytes, and pSi-1 transfection abolished the upregulation. These findings suggest that MR-1 is associated with cardiac hypertrophy in rats in vivo and in vitro.
Liu
Xiuhua
X
Dept. of Pathophysiology, PLA General Hospital, 28 Fuxing Rd., Beijing 100853, China. xiuhualiu98@yahoo.com.cn
Li
Tianbo
T
Sun
Sheng
S
Xu
Feifei
F
Wang
Yiguang
Y
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D006332:Cardiomegaly / Q000503:physiopathology*; D048429:Cell Size / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D009124:Muscle Proteins; D000804:Angiotensin II; D019808:Losartan