2004 Fiscal Year Final Research Report Summary
Analysis of Molecular Mechanisms Underlying the Initiation and Perpetuation of Tachyarrhythmias
| Project/Area Number |
15590753
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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) |
YANO Masafumi Yamaguchi University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90294628)
MATSUZAKI Masunori Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (60116754)
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| Project Period (FY) |
2003 – 2004
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| Keywords | tachyarrhythmia / atrial fibrillation / gap junction / connexin / conduction property / renin-angiotensin-aldosterone system |
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| Research Abstract |
Cardiac myocytes are connected with each other electrically and metabolically through gap junction channels composed of connexins. Many animal and human studies have described alterations in the abundance or subcellular localization of connexin proteins under a variety of pathological conditions including hypertrophy, heart failure, ischemic heart diseases, and atrial fibrillation. Many connexins, including connexin43 (Cx43), which is expressed most abundantly in the heart, have short half-lives of 1〜5 hours reflecting their rapid turnover through synthesis and degradation.
1)We examined the relative expression levels of connexin (Cx)40 and Cx43 protein and mRNAs in the right atrial myocardium from MVD (mitral valvular disease) patients with either atrial fibrillation (MVD/AF) or normal sinus rhythm (MVD/NSR). For Cx40, there were significantly lower in MVD/AF than that in MVD/NSR or in the controls (non-MVD patients with NSR), but for Cx43 showed insignificant intergroup differences. S
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erine-phosphorylated Cx40 was 〜52% greater in MVD/AF than in the controls. In human atria, Cx40 down-regulation and increased serine-phosphorylation may distort cell-to-cell communication and alter electrophysiology, leading to initiation and/or perpetuation of AF.
2)We investigated the effects of rapid electrical stimulation (RES) on the expression of Cx43 gap junction in neonatal rat cultured ventricular myocytes, and consequent changes of conduction properties. Application of rapid electrical stimulation (RES) of contraction for 60-120 min to cultured ventricular myocytes resulted in an increase of Cx43 expression (mRNA and protein). This was associated with an increase of AngII in the culture media and upregulation of activated forms of ERK, JNK and p38 MAPKs. Extracellular potential mapping revealed an increase of conduction velocity. Most of these effects of RES were prevented by losartan. A short-term RES of contraction causes upregulation of Cx43 and concomitant alterations of conduction properties through an autocrine action of AngII to activate MAPKs. Less
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[Journal Article] Rapid Electrical Stimulation of Contraction Modulates Gap-Junction Protein in Neonatal Rat Cultured Cardiomyocytes : Involvement of Mitogen-Activated Protein Kinases and Effects of Angiotensin II-Receptor Antagonist.2004
Author(s)
Inoue N, Ohkusa T, Nao T, Lee JK, Matsumoto T, Hisamatsu Y, Satoh T, Yano M, Yasui K, Kodama I, Matsuzaki M
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Journal Title
Journal of the American College of Cardiology 44
Pages: 914-922
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comparison of Expression of Connexin in Right Atrial Myocardium in Patients with Chronic Atrial Fibrillation -vs- Those in Sinus Rhythm.2003
Author(s)
Nao T, Ohkusa T, Hisamatsu Y, Inoue N, Matsumoto T, Yamada J, Shimizu A, Yoshiga Y, Yamagata T, Kobayashi K, Yano M, Hamano K, Matsuzaki M.
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Journal Title
American Journal of Cardiology 91(6)
Pages: 678-683
Description
「研究成果報告書概要(欧文)」より
