| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
(1) Marker in myocarditis
Elevation of sFas and sFasL levels at initial presentation appear to be a good serological marker to predict the prognosis of acute myocarditis. MCP-1 may play an important role in the pathogenesis of human acute myocarditis as well as in the progression of rat Experimental autoimmune myocarditis (EAM). Serum IL-10 levels may play a role m evaluation of the disease activity in patients with cardiac sarcoidosis.
(2) Therapy for myocarditis
A low dose of carvedilol has beneficial effects on rat dilated cardiomyopathy The area of myocardial fibrosis in chronic phase of Experimental autoimmune myocarditis was markedly reduced by quinapril. Bisoprolol improved survival independently, of its effect on left ventricular function by reducing sudden death in EAM. The prevention of EAM by administering the anti-CD 2 monoclonal antibody resulted from T cell depletion during theinduction phase,
(3) Gene therapy for EAM
Gene transfer into muscle by electroporation in vivo is an
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effective means of delivery of IL-10, INFγ receptor-IgG, secretary leukocyte protease inhibitor-IgG and CTLA4-IgG for the treatment of autoimmune myocarditis.
(4) Time Course of Gene Expression in EAM
α-cardiac myosin showed a 26-fold decrease and β-cardiac myosm a 3.9-fold increase at day 14. ANP and BNP increased 48- and 6.4-fold respectively at day 21 and 14. AT1 receptor, ACE and ET1 increased 22- at day 21, 6.3- at day 21 and 17-fold, respectively at day 14. Aldosterone receptor decreased 2.2-fold at day 14, but aldsterone synthethase was detected only at day 14 and 21. Interleukin (IL) -2, IL-10, interferon-γ and monocyte chemoattractant protein-1 increased 9.1- at day 14, 398- at day 21, 43- at day 14 and 142-fold at day 14, respectively. Collagen type 3, Collagen type 1 and fibronectin increased 35-, 1.7- and 45- fold at day 21. Interestingly, osteopontin showed a 4542-fold increase and it was the higtest mRNA of all at day 14.
Isoform of cardiac myosin and NP are dramatically changed in EAM. RAA and ET expressions are changed diversely in EAM time course. Cytokine, chemokine and ECM greatly increase and, especially, large numbers of osteopontin mRNA are expressed in early EAM. Less
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