[Tissue factors contributing to cardiac hypertrophy in cardiomyopathic hamsters (BIO14.6): involvement of transforming growth factor-beta 1 and tissue renin-angiotensin system in the progression of cardiac hypertrophy].
The present study was performed to determine whether transforming growth factor beta 1 (TGF beta 1) and tissue renin-angiotensin (R-A) system are involved in hypertrophic cardiomyopathy. Cardiomyopathic Syrian hamsters (Bio 14.6) aged 4 and 20 weeks were used as a model of hypertrophic cardiomyopathy and compared with age-matched F1 beta Syrian hamsters. Total RNA was extracted from the left ventricle, and the m-RNA expressions of TGF beta 1 and angiotensinogen (ATN) were examined by Northern blotting or Ribonuclease Protection Assay (RPA). The activity of angiotensin-converting enzyme (ACE) was assayed by the modified method of Tess, using crude membrane fraction prepared from left ventricle. The effect of angiotensin II (A II) on phosphatidylinositol (PI) metabolism was evaluated by the PI -or PIP2 (phosphatidylinositol 4,5-bis phosphate)-specific phospholipase C (PLC), which releases inositol-1,4,5-triphosphate (I P3) and diacylglycerol (DAG) in cardiac myocytes. The m-RNA expressions of TGF beta 1 and ATN were detected in each group of Syrian hamsters (BIO14.6 and F1 beta). TGF beta 1 m-RNA expression was markedly increased in BIO14.6 compared with F1 beta at the age of 4 weeks, and was more intensified at the age of 20 weeks, while no significant difference was demonstrated in the ATN m-RNA expression. ACE activity in the left ventricle was enhanced in 20 week-old BIO14.6 compared with age-matched F1 beta. The activities of PI- and PIP2-specific PLC were enhanced in 20 week-old BIO14.6 in response to A II stimulation. DAG and IP3, which are second messengers and activate protein kinase C. were significantly released from the cardiac myocytes of 20 week-old BIO14.6. These results suggest that the increase in expression of TGF beta 1 gene in the left ventricle may induce cardiac hypertrophy in BIO14.6, and that the exaggerated response of phosphatidylinositol metabolism to A II and the increased activity of ACE in cardiac tissue R-A system may lead to the development of cardiac hypertrophy.
Sakata
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Y
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006224:Cricetinae; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012084:Renin-Angiotensin System; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D010716:Phosphatidylinositols; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A