2002 Fiscal Year Final Research Report Summary
THE ROLE OF MATRIX METALLOPROTEINASE ON MYOCYTE REMODELING IN FAILING HEART
| Project/Area Number |
12670695
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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 | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
ONODERA Tatsuyuki Jikei University Shcool of Medicine, Lecturer, 医学部, 講師 (90194612)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Heart failure / Hepertrophy / Remodeling / Isolated myocyte / Matrix proteinase |
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| Research Abstract |
Aim: The present study was designed to investigate the role of matrix metalloproteinase (MMP) on my ocyte remodeling in spontaneously hypertensive heart failure (SHHF) rat by using MMP inhibitor. Methods : Female SHHF rats were divided into 4 groups; control group, cearly treatment group (E), middle group (M), and late treatment group (L).MMP inhibitor was administered at 6 months of age in E goup;early hypertrophic stage, 12 months of age in M group : late hypertrophic stage, and 22 months of age in L group; failing stage. The all animals were used for the following protocol at 24 months of age. Cardiac function and remodeling were evaluated by echocardiogram. Hearts were removed and perfused with media containing collagenase. Myocytes were isolated and contraction was evaluated by fieid stimulation. Then they were fixed in glutaraldehy de solution. Myocyte volume and length were measured with a Coulter Channelyzer (Coulter corp USA) and a light microscope, respectively. MMP mRNA in isolated myocyte was also evaluated by northern blotting method. Results : Left ventricular myocyte cross-sectional in SHHF rats reached a maximum of 350-400 m^2 at 3 months of age and did not change thereafter in C grourp. Left ventricular myocyte length continued to increase after 3 months of age in C group. Cardiac and myocyte shortening decreased at 24 months of age in C group.These abnormal myocyte remodeling and dysfunction were inhibited in E group, but not in M and L group.MMP mRNA decreased in E group only. Conclusions : These results suggested that early myocyte remodeling induced by MMP, plays an important role in progression to failure.
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