Role of myofibrillogenesis regulator-1 in myocardial hypertrophy
| Autor: | Tian-Bo Li, Feifei Xu, Yiguang Wang, Sheng Sun, Xiuhua Liu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Physiology Molecular Sequence Data Muscle Proteins Cardiomegaly Biology Losartan Rats Sprague-Dawley RNA interference Physiology (medical) Internal medicine medicine Animals Myocytes Cardiac Amino Acid Sequence Cell Size Homologous gene cDNA library Angiotensin II Skeletal muscle Aortic Valve Stenosis Myofibrillogenesis regulator 1 Rats Endocrinology medicine.anatomical_structure Animals Newborn Myocardial hypertrophy Cardiac hypertrophy RNA Interference Cardiology and Cardiovascular Medicine Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 290:H279-H285 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00247.2005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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