| Project/Area Number |
08670818
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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 | OSAKA CITY UNIVERSITY |
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Principal Investigator |
NEGORO Nobuo Osaka City University, Medical School, Research Associate, 医学部, 助手 (80180701)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Mikio Osaka City university, Medical School, lecturer, 医学部, 講師 (90169144)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | HYPERTENSION / ARTERIOSCLERUSIS / MOLECULAR MECHANISM / HYPERTROPHY / TRANSCRIPTION FACTOR / 血管平滑筋 / 肥大 / STAT |
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| Research Abstract |
1.Involvements of transcription factors in hypertrophy of cultured vascular smooth muscle cells (VSMC)
(1)DNA decoys are short ds-oligonucleotides corresponding to the Sp1 and ISRE,GAS,SIE,which are consensus sequences of STAT1 and STAT2. Random decoys were used as negative control. The decoys in multi-lamellar cationic liposome were intracellular-transferred to angiotensin II (AII)-treated rat VSMCs.
(2)The levels of 3H-leucine uptake in AII-treated VSMCs were inhibited by the decoy transfers for Sp1 and ISRE,GAS,SIE (69%, 58%, 66%, 41%)in association with decreases of PDGF A-chain mRNA level and 3H-thymidine uptake.
2.Involvements of STAT1 and STAT2 in hypertensive arteriosclerosis in spontaneously hypertensive rats (SHR)
(1)Transcription factors for GAS and SIE were increased in thoracic aortic medial layrs in SHR in association with increases of PDGF-A chain mRNA level.
(2)These increases were inhibited by the administration of type 1 of AII receptor antagonist.
3.Effects of cellular transfer of DNA decovs for STAT 1 and STAT 2 to femoral arteries of SHR
(1)The decoy transfer for ISRE,SIE and GAS inhibited the vascular hypertrophy index (85%, 88%, 81%) without lowering blood pressure.
(2)But the random DNA decoy did not inhibit it.
These results indicates that transcription factors for STATs are closely involved in the development of hypertensive vascular hypertrophy in vivo.
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