肥大型心筋症における肥大促進因子に関する研究 : 組織レニン-アンジオテンシン系および細胞成長因子TGF β1(Transforming Growth Factor β1)の心肥大への関与について Tissue Factors Contributing to Cardiac Hypertrophy in Cardiomypathic Hamsters (BIO14.6) : Involvement of Transforming Grawth Factor-β1 and Tissue Renin-Angiotensin System in the Progression of Cardiac Hypertrophy
肥大型心筋症における肥大促進因子に関する研究 : 組織レニン-アンジオテンシン系および細胞成長因子TGF β1(Transforming Growth Factor β1)の心肥大への関与について
Tissue Factors Contributing to Cardiac Hypertrophy in Cardiomypathic Hamsters (BIO14.6) : Involvement of Transforming Grawth Factor-β1 and Tissue Renin-Angiotensin System in the Progression of Cardiac Hypertrophy
The present study was performed to determine whether transforming growth factor β1 (TGF β1) 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 Fl β Syrian hamsters. Total RNA was extracted from the left ventricle, and the m-RNA expressions of TGF β1 and angiotensinogen(ATN) were examined by Northern blotting or Ribonuclease Protection Assay (RPA). The activity of angiotesin-converting enzyme (ACE) was assayed by the modified method of Tess, using crude membrane fraction prepared from left ventricle. The effect of angiotensinII (AII) 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 (IP3) and diacylglycerol(DAG) in cardiac myocytes. The m-RNA expressions of TGF β1 and ATN were detected in each group of Syrian hamsters (BI014.6 and FIβ). TGF β1 m-RNA expression was markedly increased in BI014.6 compared with FIβ 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 BI014.6 ccfnpared with age-matched FIβ. The activities of PI-and PTP2-specific PLC were enhanced in 20 week-old BI014.6 in response to AII stimulation. DAG and IP3, which are second messengers and activate protein kinase C, were significantly released from the cardiac myocytes of 20 week-old BI014.6. These results suggest that the increase in expression of TGF β1 gene in the left ventricle may induce cardiac hypertrophy in BI014.6, and that the exaggerated response of phosphatidylinositol metabolism to AII and the increased activity of ACE in cardiac tissue R-A system may lead to the development of cardiac hypertrophy.
Hokkaido University（北海道大学）. 博士(医学)