| Co-Investigator(Kenkyū-buntansha) |
NAGAI Ryozo Faculty of Medicine, University of Tokyo, Third Department of Internal Medicine,, 医学部(病), 助教授 (60207975)
HIRAOKA Masakazu Medical Research Institute, Tokyo Medical and Dental University, Department of C, 教授 (80014281)
NAKAO Kazuwa Faculty of Medicine, University of Kyoto, Second Department of Internal Medicine, 医学部(病), 教授 (00172263)
TADA Michihiko Faculty of Medicine, University of Osaka, First Department of Internal Medicine,, 医学部(病), 教授 (90093434)
SASAYAMA Shigetake Faculty of Medicine, University of Kyoto, Third Department of Internal Medicine,, 医学部(病), 教授 (70109007)
|
|---|
| Research Abstract |
(A) Mechanisms of Cardio-Specific Regulation of the Genes Important to cardiac Functions
As for the mechanisms of cardiac hypertrophy, we showed using an in vitro stretch-model of cultured cardiac myocytes that the intracellular signaling cascades involving MAP kinase is, at least in part, mediated by myocardial angiotensin II and that myocardial renin-angiotensin system causes hypertrophy of cardiac myocytes and interstitial fibrosis. We also clarified the mechanisms regulating the expression and transcription of cardiac genes such as cytokine (IL-6), hormones (ANP,BNP,renin, angiotensin), potassium channel, and calcium pump in response to ischemia, mechanical load, calcium, and thyroid hormone. Furthermore, we isolated the human Csx gene using the murine Csx (cardio-specific homeobox) gene as a probe and found that the amino acid sequences of human and murine Csx genes are very similar, indicating that Csx gene is highly conserved among the species.
(B) Analysis of the Genes Responsible for Myocardial Disorders
Fourteen missense mutations of the cardiac beta-myosin heavy chain gene were detected in Japanese patients with hypertrophic cardiomyopathy (HCM), and 13 out of these 14 mutations were different from those found in Caucasian patients. In 11 out of 47 affected Japanese families, there was no linkage to cardiac beta-myosin heavy chain gene, indicating the genetic heterogeneity of Japanese patients with HCM.We also identified a point mutation in tRNA-Leu gene and deletions of mitochondrial DNA in patients with mitochondrial cardiomyopathy who had cardic hypertrophy. Furthermore, we found linkage of Japanese dilated cardiomyopathy to HLA-DR locus, and Japanese long QT syndrome (Romano-Ward syndrome) to HRAS and D11S922 loci on chromosome 11p15.5.
|
