2005 Fiscal Year Final Research Report Summary
Cardiac remodeling in angiotensin-receptor knockout mice
| Project/Area Number |
16590715
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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 | Keio University |
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Principal Investigator |
YOSHIKAWA Tsutomu Keio University, Department of Medicine, Associate Professor, 医学部, 助教授 (20174906)
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| Co-Investigator(Kenkyū-buntansha) |
MEGURO Tomomi Keio University, Department of Medicine, Researcher, 医学部, 研究員 (90219957)
ANZAI Toshihisa Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (60232089)
KOHNO Takashi Keio University, Department of Medicine, Assistant, 医学部, 助手 (60327509)
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| Project Period (FY) |
2004 – 2005
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| Keywords | myocardial infarction / pressure-overload hypertrophy / aldosterone / knockout mouse |
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| Research Abstract |
Left coronary artery was ligated to induce large anterior myocardial infarction in both wild type and angiotensin type 1A knockout mice, and compared with each sham-operated mice. Four weeks after surgery, left ventricular end-diastolic and end-systolic dimensions were larger in myocardial infarction (WT/MI) than sham-operated wild type mice (WT/C). Cardiac dimensions were also higher, but to a lesser extent in angiotensin type 1A receptor knockout mice with myocardial infarction (KO/MI) than those with sham-operation (KO/C). Aldosterone synthase gene expression and protein levels in noninfarcted myocardium were higher in KO/MI than KO/C, as were in wild type mice. Coadministration of spironolactone prevented ventricular remodeling observed in KO/MI. We, next, attempted to create pressure-overloaded left ventricular hypertrophy induced by transverse aortic constriction (TAC) in these mice to determine if aldosterone production played a role in mediating cardiac remodeling independently
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from renin-angiotensin system. Pressure gradient across aorta was approximately 80 mmHg, and there was no difference between WT/TAC and KO/TAC. Left ventricular end-diastolic dimension was larger in WT/TAC than WT/C, although there was no difference between KO/TAC and KO/C. Left ventricular end-systolic dimension was larger in KO/TAC than KO/C, as were in wild type mice. Fractional shortening was lower in KO/TAC than KO/C. Myocardial brain natriuretic peptide mRNA level was higher in KO/TAC than KO/C. Type I collagen mRNA was also higher in KO/TAC than KO/C, although there was no difference in type III collagen level between the two groups. Transforming growth factor-β1 mRNA level was also higher in KO/TAC than KO/C. Spironolactone prevented these morphological and biochemical alterations. These findings suggested that local production of aldosterone played a role in mediating cardiac remodeling in both myocardial infarction and pressure-overload hypertrophy independently from angiotensin signaling. Less
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Research Products
(13 results)
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[Journal Article] Autoimmunity against the second extracellular loop of betal-adrenergic receptors induces early afterdepolarization and decreases in K-channel density in rabbits.2004
Author(s)
Fukuda Y, Miyoshi S, Tanimoto K, Oota K, Fujikura K, Iwata M, Baba A, Hagiwara Y, Yoshikawa T, Mitamura H, Ogawa S
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Journal Title
J Am Coll Cardiol 43(6)
Pages: 1090-100
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Autoimmunity against the second extracellular loop of beta1-adrenergic receptors induces early afterdepolarization and decreases in K-channel density in rabbits.2004
Author(s)
Fukuda Y, Miyoshi S, Tanimoto K, Oota K, Fujikura K, Iwata M, Baba A, Hagiwara Y, Yoshikawa T, Mitamura H, Ogawa S
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Journal Title
J Am Coll Cardiol 43(6)
Pages: 1090-1100
Description
「研究成果報告書概要(欧文)」より
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