Project/Area Number |
17590767
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Kanazawa Medical University |
Principal Investigator |
KANDA Tsugiyasu Kanazawa Medical University, General Medicine, Professor, 医学部, 教授 (40261838)
|
Co-Investigator(Kenkyū-buntansha) |
TAKEDA Takeshi Kanazawa medical University, General Medicine, Instructor, 医学部, 助手 (90340009)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | angiotensin II receptor / myocarditis / adiponectin / obesity / heart failure / in situ hybridization / 心筋肥大 / 心筋 / 再生 / 心筋炎 |
Research Abstract |
Purpose. We examined the effects of the angiotensin II receptor type1 blocker, candesartan, on myocarditis injury in a murine model of acute myocarditis. We hypothesized that candesartan improves cardiac damage by inducing cardiac expression of adiponectin. Methods and Results. We examined changes in heart failure caused by myocarditis in mice by candesartan based on induction of cardiac adiponectin expression. We intraperitoneally injected encephalomyocarditis virus in C3H mice then treated them with oral administration of candesartan (10 mg/kg/day candesartan) or vehicle (Control). The 7 day survival rate was 18% in the Control group, but 60% in the Candesartan group. The heart weight/body weight ratio in the Candesartan group was significantly lower than in the Control group. Circulating adiponectin concentrations on day 7 were significantly higher in the Candesartan group compared with Control group (7.91± 0.61 vs. 6.04±2.26.μ g/ml, P<0.05). Comparative expression of cardiac adiponectin mRNA in the Candesartan group was significantly higher than in the Control group on day 7 (55.4 ± 41.3 vs. 5.3 ± 7.7, P<0.05). Immunohistochemical staining and in situ hybridization showed that cardiac expression of adiponectin protein and mRNA was present in the Candesartan group on day 7. Conclusion. Oral administration of canndesartan improves survival and decreases myocardial damage in mice with viral myocarditits and induces expression of cardiac adiponectin. The induction of adiponectin might provide cardioprotective effects against acute heart failure due to viral myocarditis.
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