| Project/Area Number |
14570638
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
TAKANO Hiroyuki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT, 大学院・医学研究院, 助手 (60334190)
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| Co-Investigator(Kenkyū-buntansha) |
KOMURO Issei CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (30260483)
YOSHIDA Katsuya CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (10191579)
NAGAI Toshio CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, LECTURER, 医学部附属病院, 講師 (00334194)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | PPARγ / thiazolidinedione / cardiac hypertrophy / heart failure / angiotensin II / knockout mouse |
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| Research Abstract |
Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARs have three isoforms, α, β(or δ), and γ. It has been conceived that PPARγ is expressed predominantly in adipose tissue and promotes adipocyte differentiation and glucose homeostasis. Recently, synthetic antidiabetic thiazohdinediones (TZDs) and natural prostaglandin D2 (PGD2) metabolite, 15-deoxy-Δ^<12,> ^<14>-prostaglandin J2 (15d-PGJ2), have been identified as ligands for PPARγ. In the present study, we demonstrated that PPARγ ligands, troglitazone, pioghtazone and rosiglitazone, inhibit Ang II-induced hypertrophy of neonatal rat cardiac myocytes. The pressure overload-induced cardiac hypertrophy was more prominent in PPARγ^<+/-> mice than in WT mice. Treatment with a PPARγ ligand, pioglitazone, inhibited the pressure overload-induced cardiac hypertrophy strongly in WT mice and moderately in PPARγ^<+/->mice. These results suggest that PPARγ-dependent pathway inhibits the development of cardiac hypertrophy. Althoughthe molecular mechanism of how PPARγ suppresses cardiac hypertrophy remains to be determined, it is conceivable that PPARγ may suppress the development of cardiac hypertrophy by antagonizing the activities of transcription factors such as AP-1, STAT3 and GATA4. Recently, many reports suggest that insulin resistance and hyperinsulinemia are involved in cardiac hypertrophy. Our study suggests the potential clinical efficacy of the thiazolidinediones for prevention of cardiac hypertrophy. Further studies are necessary to elucidate whether inhibition of cardiac hypertrophy by PPARγ ligand improves prognosis or not.
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