动脉粥样硬化血栓疾病的炎症和发病机制课件.ppt

1、Intrinsic Vascular Wall Cells:n Endotheliumn Smooth Muscle CellsInflammatory Cells:n Macrophagesn T Lymphocytesn Mast CellsTunicaMediaIntimaSmooth musclecellsn Binds monocytes and lymphocytes-Cells found in atheroman Expressed by endothelium over nascent fatty streaksn Expressed by microvessels of t

2、he mature atheromaLi H et al.Arterioscler Thromb 1993;13:197-204.Li H et al.Arterioscler Thromb 1993;13:197-204.3 weeks on atherogenic dietn A potent mononuclear cell chemoattractantn Produced by endothelial and smooth muscle cellsn Localizes in human and experimental atheromaGu L et al.Mol Cell 199

3、8;2:275-281.Gu L et al.Mol Cell 1998;2:275-281.Gu L et al.Mol Cell 1998;2:275-281.051015202530Oil Red Staining%Aortic Surface StainedTime on Diet:12 14 weeks+/+-/-*+/+-/-20 25 weeks *P=0.001 compared to+/+*p=0.005 compared to+/+ActivationDivisionn A potent monocyte activator and co-mitogenn Produced

4、 by endothelial and smooth muscle cellsn Localizes in human and experimental atheromaRosenfeld ME et al.Am J Pathol 1992;140:291-300.Clinton SK et al.Am J Pathol 1992;140:301-316.IntimalM-CSFinAtheromaSmith JD et al.Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating fa

5、ctor(op)and apolipoprotein E.Proc Natl Acad Sci U S A 1995;92:8264-8268.Qiao JH et al.Role of macrophage colony-stimulating factor in atherosclerosis:studies of osteopetrotic mice.Am J Pathol 1997;150:1687-1699.Rajavashisth T et al.Heterozygous osteopetrotic(op)mutation reduces atherosclerosis in LD

6、L receptordeficient mice.J Clin Invest 1998;101:2702-2710.Rajavashisth T et al.J Clin Invest 1998;101:2702-2710.Rajavashisth T et al.J Clin Invest 1998;101:2702-2710.107Fatty Lesions in Aortic Root(m2/section)106105104103(10)*(4)*(12)Genotypeop/+/+op/opM-CSFMCP-1VCAM-1LumenLipidCoreFibrous capShould

7、erIntimaMediaElasticlaminInternalExternalnThrombogenicity of the lipid coreIllustration courtesy of Michael J.Davies,M.D.Libby P.Circulation 1995;91:2844-2850.+SynthesisBreakdownLipid coreIL-1TNF-MCP-1M-CSFFibrouscapCD-40LGalis ZS et al.J Clin Invest 1994;94:2493-2503.ThrombusFibrous cap1 mmLipid co

8、reIllustration courtesy of Frederick J.Schoen,M.D.,Ph.D.nWeakening of the fibrous capIllustration courtesy of Michael J.Davies,M.D.CD40Mach F et al.Circulation 1997;96:396-399.Tissue FactorLog FluorescenceCell Numbers1601208040016012080400100101102103100101102103rCD40L/-CD40LrCD40LT cell/membranes/-CD40LT cell/membranesMach F et al.Circulation 1997;96:396-399.Henn V et al.Nature 1998;391:591-594.nLesion initiationnLesion progressionnThrombotic complications