| Co-Investigator(Kenkyū-buntansha) |
YOSHIYAMA Minoru Osaka City University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (30240956)
YOSHIKAWA Junichi Osaka City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60275245)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We have demonstrated as following.
1.Angiotensin II induced MCP-1 gene expression in cardiac fibroblasts. The angiotensin II-induced activation of ASK-1 followed by p38MAPK and NF-kB signaling in cardiac fibroblasts is partially involved in myocardial MCP-1
2.Dominant negative mutants of JNK, ASK-1 and c-Jun significantly inhibited PAI-1 mRNA expression and protein synthesis in both cardiomyocytes and fibroblasts. Moreover, a dominant negative mutant of JNK also significantly prevented the induction of PAI-1 mRNA expression by endothelin-1 and phenylephrine. In conclusion, G-protein coupled receptor agonist-induced PAI-1 expression is partially mediated through JNK activation.
3.We investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler-echocardiography. Histologically, hypertrophy of cardiomyocyt
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es, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.
4.The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF- and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (Control group), or medium (Medium group) were injected into rat hearts one hour after left coronary artery occlusion. At one week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E/ A ratio and capillary density of the infarcted region were most improved in the VEGF group. In conclusion, this combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI. Less
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