2002 Fiscal Year Final Research Report Summary
Viral infection and Cardiomyopathy: enteroviral Replication and Cardiocyte Injury in the Recipient Hearts of Dilated Cardiomyopathy and Perforin Knockout Mice with Viral Myocarditis
| Project/Area Number |
13670757
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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 | Osaka Medical College |
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Principal Investigator |
DEGUCHI Hirofumi Osaka Medical College Faculty of Medicine Assistant Professor, 医学部, 助教授 (90131341)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIOKA Shigekazu Osaka Medical College Faculty of Medicine Research Associate, 医学部, 助手 (20319528)
UKIMURA Akira Osaka Medical College Faculty of Medicine Research Associate, 医学部, 助手 (50257862)
KITAURA Yasushi Osaka Medical College Faculty of Medicine Professor, 医学部, 教授 (50084950)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Dilated cardiomyopathy / Cardiac transplantation / Viral myocarditis / Coxsackievirus / Cytokine / Perforin / Knockout mouse / PCR |
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| Research Abstract |
(A) Enteroviral detection and cytokine expression in the recipient hearts from patients with dilated cardiomyopathy (DCM)
We examined myocardial specimens obtained from 30 DCM patients who underwent heart transplantation.
(1) Semiquantitative analysis of histological findings: histological findings showed inflammatory cell infiltration in 14DCM patients (47%) and fibrosis in 18 patients (60%). 4 patients (13%) had active myocarditis.
(2) Cytokine expression in the heart: We elucidated the expression of inflammatory cytokine in the recipient hearts using the ABI PRISM7700. IL-1β mRNA was overexpressed in 5 of 12 DCM patients (42%), and IL-8 in 5 of 12 (42%). Expression of IL-12p35, IL15 and IFN-γ mRNA raised respectively in 1 of 12 patients (8%). The findings suggest IL-1β and IL-8 play significant role in the inflammatory lesion in the myocardium of DCM.
(B) Experimental Coxsackievirus B3 Myocarditis in Perforin Knockout (pfk) Mice
We examined light and electron microscopic (EM) changes of the myocardium obtained from pfk and wild (C57BL/6) mice with Coxsackievirus B3 myocarditis. In wild mice many cardiocytes underwent necrosis with infiltration of lymphocytes and macrophages. By immuno EM perforin were often observed in the granules of lymphocytes. These lymphocytes showed close contact with cardiocytes. In pfk mice cardiocyte necrosis was less than in wild mice, although significant number of lymphocytes infiltrated in the myocardium. These findings suggest that pfk plays an important role in the development of lymphocyte-mediated cardiocyte injury.
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