心力衰竭的信号通路-课件幻灯

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,1,田小利,人类群体遗传室,北京大学分子医学研究所,死亡,代偿期,失代偿期,恶化期,结构和功能的改变,-,重塑,高血压，冠心病,遗传，心肌病,瓣膜病，先心病,*,*,*,*,心力衰竭,心力衰竭的诱因和病理过程,2,激素、药物、,神经递质,膜受体,第二信使,Ca,2+,离子通道,活性肽,心力衰竭,心律失常,线粒体活性氧,心脏病相关基因,活性肽,(1),(1),心,力,衰,竭,心力衰竭可能的开展根底,3,心力衰竭,临床诊断,遗传学,通道电生理学,神经和信号转导,心肌重塑的关键分子,细胞水平鉴定,动物模型,计算机数字化模拟,3-D,结构研究,作用机制及早期干预,新药靶点及可药性,早期诊断标记的可能性,目前主要研究的内容,4,AOGEN,Renin,ACE,ANG I,ANG II,5,Salt/water balance,Contraction of VSMC,Mitogenic effects,Neurotransmitter,Hormone-stimulation factor,Cardiac output,6,PLD,PLC,AII,a,g,b,PC,PA,DAG,Choline,IP3,PIP2,PKC,Mek,Mapk,Stats,ER,Ca,+,Shc,Jaks,SIE,C-fos,C-Jun,Stats,SOS,Grb2,Ras,Raf,GTP,C-myc,Egr,Ca,+,Ca,+,Ca,+,Ca,+,7,AOGEN,Renin,ACE,ANG I,ANG II,Kallikrein,Tonin,Chymotrypsin,Capthepsin G,Chymase,Kallikrein,Chymotrypsin,Capthesin G,8,9,50,40,30,20,10,0,Captopril,Chymostatin,Cap+Chymo,Cap+Aprot,CV 11974,%phenylephrine,ANG1 perfusion,isolated aorta,Nishimura,1998,Chymase:,Ang II forming enzyme,in vitro,Found,cloned and characterized by,Dr.Hidenori Urata,Urata,1990,ACE,Chymase,Fe,Ad,Tian,1996,Renin,Angiotensinogen,ACE,Angiotensin I,Angiotensin II,AT1,AT2,Angiotensinogen,Renin,ACE,AT1,AT2,10,Angiotensinogen,Renin,Angiotensin 1,Angiotensin 2,Kininogen,Kallikrein,Bradykinin,Inactive peptides,ACE,RAS,(AII/AT1),AS,(a1),ETS,(ET-1/ETA),11,12,Angiotensin 1,Bradykinin,AcSDKP,(N-acetyl-Ser-Asp-Lys-Pro),Angiotensin II,Cell growth.etc,.,degraded fragments,degraded fragments,Actiate TGF-,signaling,13,Fleming I et al.,Physiology.,2005;20:91-5.,ACE,NH,2,ACE inhibitor,Extracellular,Cytosol,COOH,Nucleus,Gene expression(ACE,COX-2),CK2,JNK,MKK7,P,JNK,cJun,cJun,P,cJun,P,cJun,P,cJun,P,AP-1,cJun,P,cJun,P,Clinical significance of this pathway is under investigation,Angiotensinogen(M235T),Together with ACE-D,associated male LVH,CAD,AT1(A1166C),Associated male LVH,14,15,ACE(I/D),Earlier than 1994:tends to associated,Later than 1994:tends to not associated,LVH of man,not woman,Degree,not frequency of LVH,ACEI treatment,QT dispersion,heart rate variability,Exercise-induced LHV,16,Ao,rt,a,Lun,g,Ki,dn,ey,Brai,n,Li,v,er,L.,V,en,tr,ic,le,R.,ve,nt,ri,cl,e,Sk,.mu,scle,rAC,E,hA,CE,17,SD,TGR,50,60,70,80,90,100,110,-10,-9,-8,5,-8,-7,5,50,60,70,80,90,100,110,-10,-9,-8,5,-8,-7,5,SD,TGR,30,25,20,15,10,5,0,SD,TGR,AII(pg/g),AI on coronary artery flow,Cardiac AII,18,ACEI,1,6,1,8,2,0,2,2,2,4,2,6,2,8,3,0,LV/B,SD-sh,SD-ab,TGR-ab,TGR-sh,L,V,/,B,(,m,g,/,g,),0,1,2,3,4,5,6,7,8,ANF,Col3,%,G,A,P,D,H,0,20,40,60,80,100,120,140,160,180,S,D,-,s,h,T,G,R,-,s,h,S,D,-,a,b,T,G,R,-,a,b,S,D,-,s,h,T,G,R,-,s,h,S,D,-,a,b,T,G,R,-,a,b,ANF,Col3,GAPDH,SD-sh,SD-ab,TGR-ab,TGR-sh,S,B,P,(,m,m,H,g,),19,20,Age 10 months,col1,col3,GAPDH,NTGR,TGRL1172,TGRL1173,Lisinopril,AcSDKP,21,ACE,TGF-,TGF-R1,Smad3,Smad2,Smad4,Col,TGF-,GAPDH,Smad3-p,Smad3,Smad2-p,Smad2,AcSDKP,NTGR,TGRL1172,TGRL1173,NTGR,TGRL1172,TGRL1173,Lisinopril,AcSDKP,NTGR,TGRL1172,TGRL1173,Lisinopril,AcSDKP,22,23,Transcriptional machinery,C,m,G,H-act,Epigenetic modification,Definition of CG island in RAS promoters,24,ATG,TSS,5-UTR,1 kb,CG sites,CTGTCCCTGGCTCCTTCCCTGATCCCAC,CG,CCAGCCTCACCCCA,CG,GTTCCTCCATTGCC,CCACCTCCCACTG,CG,C,CG,C,CG,GGCCTCTGCCAGGGTCAAGGGGCTTCCCCCCTCTGGCAG,CAGA,CG,CCATGGTGC,CG,AGGTGGCCTCCACAAC,CG,CCCTGTG,CG,CCAATAGGACAAGACT,GTCCTCCCTCCCCCACACTTGTCACTTT