1995 Fiscal Year Final Research Report Summary
Development of new diagnostic and therapeutic methods and animal models of cardiovascular diseases using smooth muscle myosin heavy chain isoforms.
| Project/Area Number |
05557040
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gunma University School of Medicine (1995)
The University of Tokyo (1993-1994) |
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Principal Investigator |
NAGAI Ryozo Gunma University School of Medicine 2nd Dept of Int Med, Professor, 医学部, 教授 (60207975)
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| Co-Investigator(Kenkyū-buntansha) |
NABESHIMA Youich National Neuroscience Center, Director, 神経センター, 部長 (60108024)
KURO-O Makoto National Neuroscience Center, research fellow, 神経研究所, 研究員
ARAI Masashi Gunma University School of Medicine 2nd Dept of Int Med, Assistant, 医学部, 助手 (60270857)
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| Project Period (FY) |
1993 – 1995
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| Keywords | SMOOTH MUSCLE, / MYOSIN, / SM1 / 2 GENE, / ATHEROSCLEROSIS, / TRANSGENIC MOUSE, / AORTIC DISSECTION, / AGING, / IMMUNOASSAY |
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| Research Abstract |
We previously demonstrated that rabbit and rat smooth muscles contain at least three types of MHCs ; SM1 (204kDa), SM2 (200kDa) and SMemb (200kDa). SM1 and SM2 are two smooth muscle specific MHC isoforms arising from a single gene, and SMemb is a third type of MHC isoform abundantly expressed in embryonic aortas. The expression of three MHC isoforms is developmentallyregulated.
The presence of developmentallyregulated MHC isoforms in vascular smooth muscles provides importantmoleculartools to investigate the molecularmechanism underlying vascular diseases. We first developed an immunoassay for smooth muscle myosin heavy chain isoform (SM1) which could be released into circulation following vascular injury. This assay is sensitive and specific enough to detect circulating SM1 after acute aortic dissection in clincal cases. The sensitivity and specificity of our SM1 assay for diagnosis of aortic dissection were 87% and 97%, respectively.
In order to understand the molecular mechanisms underlying smooth muscle de-differentiation and proliferation occurring in atherosclerosis and restenosis, we characterized the promoter region of the SMemb gene. In this study, we identified a cis element and a transcription factor, BTEB-2, which coordinately regulate the SMemb gene.
We furthemore developed a transgenic mouse in which a single gene was coincidentally knocked out, which resulted in accelerated aging process including atheosclerois, pulmonary emphysema and reduced insulin secretion.
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[Publications] Takewaki S,Kuro-o M,Hiroi Y,Watanabe M,Noguchi T,Nakahara K,Aikawa M,Manabe I,Ohkubo A,Yazaki Y,Nagai R.: "Activationof Na^+-H^+antipoter (NHE-1) gene expression during growth, hypertrophy and proliferation of the rabbit cardiovascular system" J.Mol.Cell Cardiol.27. 729-742 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Kimura K,Nagai R,Sakai T,Aikawa M,Kuro-o M,Kobayashi N,Shirato I,Inagami T,Oshi M,Suzuki N,Oba S,Mise , Tojo A,Hirata Y,Goto A,Yazaki Y,Omata M.: "Diversity and variability of smooth muscle phenotypes of renal arterioles as revealed by myosin isoform expression." Kidney Int. 48. 372-382 (1995)
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[Publications] Hiroi J,Kimura K,Sakai T,Aikawa M,Kuro-o M,Kobayashi N,Shirato I,Inagami T,Oshi M,Suzuki N,Oba S,Mise N,Tojo A,Hirata Y,Goto A,Yazaki Y,Omata M,Nagai R.: "Expression of a nonmuscle myosin heavy chain in glomerular cells differentiates various types of glomerular disease in rats." Kidney Int. (in press.).
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「研究成果報告書概要(欧文)」より
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[Publications] Suzuki J,Isobe M,Aikawa M,Kawauchi M,Shiojima I,Kobayashi N,Tojo A,Kimura K,Nishikawa T,Sakai T,Sekiguchi M,Yazaki Y,Nagai R.: "Nonmuscle and smooth muscle myosin heavy chain expression in rejected allograft-a study in rat and monkey models." Circulation Res.(in press.).
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「研究成果報告書概要(欧文)」より
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