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書式設定,書式設定,第 2,第 3,第 4,第 5,*,書式設定,書式設定,第 2,第 3,第 4,第 5,*,New Strategies for Immune-mediated Heart Diseases,Mitsuaki,Isobe,Department of Cardiovascular Medicine,Tokyo Medical and Dental University,China-Japan Cardiovascular Forum 2008,Immune-mediated heart diseases,Ischemia-reperfusion injury,Atherosclerosis,Restenosis,Cardiac allograft rejection,Cardiac allograft vasculopathy,Myocarditis,Congestive heart failure,Arrhythmia,Immune-mediated heart diseases,Ischemia-reperfusion injury,Atherosclerosis,Restenosis,Cardiac allograft rejection,Cardiac allograft vasculopathy,Myocarditis,Congestive heart failure,Arrhythmia,Inflammation in coronary arteriosclerosis and atherogenesis,PPAR,(Peroxisome proliferator-activated receptor-),NFB,Acute cardiac allograft rejection,Ectopic heart transplantion,recipients:C3H/He,donors:BALB/c,full mismatch,Administration of,pioglitazone(3mg/kg/day),to the,recipient mice.,Murine heart transplantation,Survival Rate,Postoperative Days,Pioglitazone,(3mg/kg/day),Control chow,Prolongation of heart graft by pioglitazone,1,0.8,0.6,0.4,0.2,0,10,20,30,40,50,60,70,*,*,p0.05,Kosuge,Suzuki,Isobe:Circulation 113:2613-2622,、,2006,0.8,0.6,0.4,0.2,0,Optical Density,R,R+Pio10,-6,M,R+S,R+S+Pio10,-6,M,R+S+Pio10,-7,M,R+S+Pio10,-5,M,R:responder,(recipient),S:stimulator,(donor),Pio:pioglitazone,*,*,*,p0.05,Suppression of T cell Proliferation by Pioglitazone in Mixed Lymphocyte Reaction,*,Chronic cardiac rejection,Graft arterial disease(GAD),RCA,LAD,LCX,8-y-o boy,Small,arteries,Myocardium,Accelerated coronary sclerosis,Graft vasculopathy,Cardiac allograft vasculopathy,Pathology:,Diffuse intimal,thickening of small to large,coronary arteries,Pathology:,Diffuse intimal,thickening of small to large,coronary arteries,Risk factors:,CMV infection,episodes of acute rejection,Risk factors:,CMV infection,episodes of acute rejection,Therapy:,?,Therapy:,?,Progression:,months to years,Progression:,months to years,Chronic cardiac allograft rejection,Cardiac allograft vasculopathy,recipients:C57BL/6,donors:Bm12,classII mismatch,-1,0 7 14 21 28 35 42 49 56 days,sacrifice,Control chow,Pioglitazone,(3mg/kg/day),Telmisartan,(10mg/kg/day),8 Weeks after Transplantation,Luminal occlusion(%),p0.05,Control,Pioglitazone,Attenuation of Graft Arteriosclerosis by Treatment with Pioglitazone or Telmisartan,Control,Pioglitazone,Telmisartan,p0.05,Control,Telmisartan,Kosuge,Suzuki,Isobe:Circulation 2006,Aorta,SMCs,activated splenocytes,Proliferation,SMC Proliferation Assay,Pioglitazone,telmisartan,Suppression of SMC proliferation?,Suppression of SMC Proliferation after Interaction with Splenocytes by Pioglitazone or Telmisartan,SMCs+Pio10,-6,M,Sp+SMCs+Pio10,-7,M,Sp+SMCs+Pio10,-6,M,Sp+SMCs+Pio10,-5,M,0,5.0,4.0,3.0,2.0,1.0,Optical,Density,SMCs,Sp+SMCs,*,*,*,0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,SMCs,SMCs+Tel 10,-6,M,FBS+SMCs,*,*,*,FBS+SMCs+Tel 10,-7,M,FBS+SMCs+Tel10,-6,M,FBS+SMCs+Tel 10,-5,M,FBS+SMCs+Tel 10,-5,M+GW,Summary 1,PPAR is associated with pathophysiology of immune-mediated heart diseases.,PPAR-agonists(pioglitazone and telmisartan)are effective in suppressing experimental cardiac allograft rejection(acute rejection and allograft vasculopathy).,References,Kosuge,Suzuki,Isobe:Circulation 113:2613-2622,2006,Isobe,Kosuge,Suzuki:ATVB,26:1447-1456,2006,Kosuge,Suzuki,Isobe:ATVB,26:2660-2665,2006,Onai,Suzuki,Maejima:Am J Physiol,292,H530-538,2007,Kosuge,Suzuki,Isobe,Transplanation,in press,Maejima,Suzuki,Okada,Isobe:in submission,Inflammation in coronary arteriosclerosis and atherogenesis,PPAR,(Peroxisome proliferator-activated receptor-),NFB,LPS,TNF,NFB,TCR,TCell,Stimuli,Anoxia,Reactive oxygen species,LPS,Cytokines(IL-1,TNF),Re-oxygenation,Lipoprotein,Thrombin,Gene Expression,Cytokines(IL-1,TNF),iNOS,COX-2,Adhesion molecules(ICAM-1,VCAM-1),Immunoreceptors(MHC class I,II),IL-6,M-CSF,GM-CSF,Chemokines(MCP-1,),Acute phase protein(CRP,),Role of NF-kB in Cardiovascular Diseases,Heart failure,Vascular remodeling,Allograft rejection,Myocarditis,Reperfusion injury,Ventricular remodeling,NF-B Activation,NF-B,decoy-Mechanism of Action-,Cell,Membrane,Nucleus,Cis-Element,Inflammatory genes,Decoy,I-B,p50,p65,I-,k,B kinases,k,I-,B kinases,Stimuli,Degradation,I-B,P,I-B,p50,p65,Decoy,mRNA,Inflammatory,molecules,p50,p65,p50,p65,p50,p65,X,X,Acute Myocarditis,Experimental Allergic Myocarditis in Rats,Immunization,Lewis rats were immunized with porcine cardiac myosin.,In vivo gene transfer,Injection of HVJ-liposome-NFB decoy at coronary cusp,Day 0,7 or 14,21,days after transfection,FITC-labeled Decoy in Rat Heart,NFkB decoy reduces extent of autoimmune myocariditis,Control,(injection at day 7),(Yokoseki O,Isobe M,Circ Res 2001),0,20,40,60,80,100,(%),UT,SD,day0,day7,day14,Myocarditis-affected area,NFkB decoy,Method of gene transfer to cardiac allograft,Donor,Heart,HVJ-,HVJ-liposome,Donor,Recipient,Histological,analysis,Transfection:10 min,4C,Ischemic time:30 min,Decoy Transfection,28,days,VCAM-1,PDGF-B mRNA,EvG staining,Scramble,decoy,NFB,decoy,Effect of NFB decoy
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