2001 Fiscal Year Final Research Report Summary
Molecular Analysis of Atrila fibrillation - approach through Ca2+ regulatory proteins -
| Project/Area Number |
12670671
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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 | Yamaguchi University |
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Principal Investigator |
OHKUSA Tomoko Yamaguchi University, School of Medicine, Research Associate, 医学部, 助手 (00294629)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUZAKI Masunori Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (60116754)
YANO Masafumi Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (90294628)
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| Project Period (FY) |
2000 – 2001
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| Keywords | atrial fibrillation / Ca2+ regulatory protein / sarcoplasmic reticulum / molecular biology / ryanodine receptor / Ca2+-ATPase / inositol trisphosphate receptor |
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| Research Abstract |
Abnormal intracellular Ca^<2+> homeostasis occurs in chronic atrial fibrillation (AF). The intracellular Ca^<2+> concentration is regulated by ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors. We recently reported alterations in ryanodine receptors in atrial tissue in chronic AF. Here, we examine whether AF patients have alterations in atrial IP3 receptors. We analyzed IP3 receptor expression in the right atrial myocardium from 13 mitral valvular disease (MVD) patients with AF (MVD/AF), 5 MVD patients with normal sinus rhythm (MVD/NSR), and 8 control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue. The relative expression level of IP3 receptor was significantly greater in MVD/AF (0.75 ± 0.26) than in MVD/NSR (0.42 ± 0.13, p<0.05), and both were significantly above control (0.14± 0.08). The relative expression level of IP3 receptor mRNA was significantly greater in MVD/AF (0.028±0.008) than in control (0.015±0.004, p<0.01), but MVD/AF patients did not differ from MVD/NSR (0.020±0.006) patients. The relative expression levels of IP3 receptor protein and mRNA were higher in patients with left atrial dimension 【greater than or equal】40 mm, pulmonary capillary wedge pressure 【greater than or equal】10 mmHg, and right atrial pressure 【greater than or equal】5 mmHg. IP3 receptors were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca^<2+> homeostasis and initiating and/or perpetuating AF.
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