2004 Fiscal Year Final Research Report Summary
Hypercholesterolemia induces left ventricular hypertrophy and fibrosis via increase of aldosterone biosynthesis.
| Project/Area Number |
15590772
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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 |
MOCHIZUKI Seibu Jikei University School of Medicine, Professor, 医学部, 教授 (20130205)
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| Co-Investigator(Kenkyū-buntansha) |
IKEWAKI Katsunori Jikei University School of Medicine, Lecturer, 医学部, 講師 (40287199)
YOSHIDA Hiroshi Jikei University School of Medicine, Lecturer, 医学部, 講師 (30333529)
YAMANE Teiichi Jikei University School of Medicine, Lecturer, 医学部, 講師 (40297429)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Cholesterol / Cardiac hypertrophy / Myocardial Infarction / Aldosterone / Renovascular hypertensive rat / Eprelenone / Cardiac fibrosis |
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| Research Abstract |
[Purpose]Supply of cholesterol is essential for biosynthesis of steroid hormones including aldosterone(Aldo). However, it remains to be elucidated that hypercholesterolemia has a direct effect on cardiac hypertrophy and fibrosis. Therefore, we studied whether hypercholesterolemia induces left ventricular(LV) hypertrophy and myocardial fibrosis via increase of Aldo biosynthesis in rabbit model. [Methods]New Zealand white rabbits weighing 3kg were fed a normal chow [control group (C group)] or enriched chow with 2% cholesterol [hypercholesterol group (H group)] for 8 weeks. Plasma concentrations of serum lipids, angiotensin-II(Ang-II), and Aldo were measured. Cardiac diastolic function was evaluated by using echocardiography measuring LV inflow rate. After 8 weeks feeding, hearts were excised and histomorphological analyses were performed.
[Results]High cholesterol diet induced significant increases in total cholesterol and low density lipoprotein cholesterol concentrations. Plasma Aldo concentration was increased and Ang-II concentration was suppressed significantly in H group compared with C group. LV weight/body weight and myocardial fibrosis in H group were also increased compared with C group. In echocardiography, cardiac diastolic function was impaired in H group compared with C group. [Conclusion]The result of our study clearly demonstrates that hypercholesterolemia increases Aldo biosynthesis, induces LV hypertrophy and exerts myocardial fibrosis leading to diastolic dysfunction. Therefore, anti-hypercholesterolemic treatment may contribute to prevent LV hypertrophy and diastolic dysfunction in hypercholesterolemic patients.
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