医学免疫学课件：C反应蛋白与心肌梗塞

1、C-reactive Protein and Myocardial InfarctionOUTLINEC-reactive protein（CRP）IntroductionStructureFunctionMyocardial infarctionIntroductionEndothelial cell of coronary arteryPathogenesisLeukocyte behaviors and LDL ingestionComplement activation by CRPEndothelial dysfunctionAdhesion induced by CRPSummar

2、y of CRP functionsProspectiveReferenceIntroduction of CRPC-reactive proteinDiscovered by Tillet and Francis in 1930Acute phase protein in serumSynthesized in LiverActivated by IL-6，IL-8，TNFStructure of CRPC-reactive protein at the interface between innate immunity and inflammation. EXPERT REVIEW OF

3、CLINICAL IMMUNOLOGY 2008 4;3:379-390A face: binding sites of C1q or FcR B face: binding sites of PC & Ca2+Function of CRPLigandsPCNuclear antigenComplement activationC1qComplement Activation/kbates/Immunology/images/figure_02_43.jpgFunction of CRPLigandsPCNuclear antigenComplement activationC1qBindi

4、ng to Fc receptorsFcR categoriesDifferent kinds of effector cellsBinding to Fc receptors/data/journals/jac/23098/m_06012_gr1.jpegAnti-inflammationC-Reactive Protein - An Activator of Innate Immunity and a Modulator of Adaptive Immunity；Immunologic Research 2004; 30/3:261277.Function of CRP in SLEC-r

5、eactive protein at the interface between innate immunity and inflammation. EXPERT REVIEW OF CLINICAL IMMUNOLOGY 2008 4;3:379-390Function of CRPA face C1q or FcRB face PC and Ca2+Introduction of myocardial infarctionAcute myocardial infarction（AMI）Heart muscle damage caused by ischemiaC-reactive prot

6、einhttp:/pro-medica.ru/iz-regionov/946-aorto-koronarnoe-shuntirovanie-aksh-v-bryanskeEndothelial cells At the internal lumenVarious functions：Prevention of platelet and leukocyte adhesionInfluence on vasodilation and vasoconstrictionRegulation of blood flow Endothelial dysfunction nitricoxide (NO) p

7、rostacyclinMatsuzawa,Y.,Lerman,A.,2014.Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coron.ArteryDis.25,713724.Anatomy and functions of normal endotheliumYasushi Matsuzawa and Amir Lerman；Endothelial dysfunction and coronary artery disease: assessment, pr

8、ognosis, and treatment. Coronary Artery Disease 2014, 25:71372415Your textAtherosclerosisInflammationLeukocyteComplementactivationCRPInflammation mediation of myocardial infarctionLeukocyte Behavior in AtherosclerosisSwirski, S.F.K.,Nahrendorf,M.N.,2013. Leukocyte behavior in atherosclerosis, myocar

9、dial infarction, and heart failure.Science339,161166.NLRP3 inflammasomeIL-Anders Hovland, et al. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis. Atherosclerosis 241 (2015) 480e494Complement activation in atherosclerosisSteffen U. Eisenha

10、rdt a,b,*,1, Julia Starke a,1, Jan，et al. Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDLemonocyte interactions. Atherosclerosis 224 (2012) 384e393mmLDL：minimally modified low-density lipoproteinpCRP：pentameric CRPmCRP：monomeric formCRP modulating the binding of mmLDL to

11、monocytesCRP modulating the binding of mmLDL to monocytesSteffen U. Eisenhardt a,b,*,1, Julia Starke a,1, Jan，et al. Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDLemonocyte interactions. Atherosclerosis 224 (2012) 384e393pCRP reduces the binding mCRP promotes the binding

12、In vitro：Decrease of endothelial NO synthesis（eNOS）Inhibition of endothelium-dependent NO-mediated vasodilation In vivo？Role of CRP in endothelial dysfunctionHein, T.W.,Singh,U.,Vasquez-Vivar,J.,Devaraj,S.,Kuo,L.,Jialal,I.,2009.Human C-reactive protein induces endothelial dysfunction and uncoupling

13、of eNOS in-vivo.Atherosclarosis206(1),6168.Role of CRP in endothelial dysfunctionHein, T.W.,Singh,U.,Vasquez-Vivar,J.,Devaraj,S.,Kuo,L.,Jialal,I.,2009.Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in-vivo.Atherosclarosis206(1),6168.L-NAME: inhibitor ofNOSSNP: sodium

14、 nitroprussideHuSA: humanserum albuminABCDRole of CRP in endothelial dysfunctionHein, T.W.,Singh,U.,Vasquez-Vivar,J.,Devaraj,S.,Kuo,L.,Jialal,I.,2009.Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in-vivo.Atherosclarosis206(1),6168.DHE stainingROS（reactive oxygen spe

15、cies）In vitro：Decrease of endothelial NO synthesis（eNOS）Inhibition of endothelium-dependent NO-mediated vasodilation In vivoDecrease of endothelial NO synthesis（eNOS）Inhibition of endothelium-dependent NO-mediated vasodilation Role of CRP in endothelial dysfunctionHein, T.W.,Singh,U.,Vasquez-Vivar,J

16、.,Devaraj,S.,Kuo,L.,Jialal,I.,2009.Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in-vivo.Atherosclarosis206(1),6168.C-reactive protein induced inflammationSavoia,C.,Schiffrin,E.L.,2007.Reduction of C-reactive protein and the use of anti-hypertensives. Vasc Health Ri

17、sk Manag 3(6),975983.VCAM：Vascular cell adhesion moleculeICAM：Intercellular adhesion moleculeROS：reactive oxygen speciesPossible mechanisms of myocardial infarctionInflammation involved in the various aspects of atherogenesis CRP directly involved in the inflammationEndothelial dysfunctionComplement

18、 activationatherosclerosis Enhancement and plaque ruptures/2012/03/understanding-c-reactive-proteing-crp-on-your-lab-report/Representation of CRP-mediated effects on atherosclerosis and CHDAmit Kumar Shrivastava. C-reactive protein, inflammation and coronary heart diseaseReview Article. The Egyptian

19、 Heart Journal, Volume 67, Issue 2, June 2015, Pages 89-97 ProspectiveCRP-targeting drugsLeukocyte-targeting treatmentsBetter life style ReferencesC-reactive protein at the interface between innate immunity and inflammation. EXPERT REVIEW OF CLINICAL IMMUNOLOGY 2008 4;3:379-390C-Reactive Protein - A

20、n Activator of Innate Immunity and a Modulator of Adaptive Immunity；Immunologic Research 2004; 30/3:261277.Matsuzawa,Y.,Lerman,A., Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coron.ArteryDis. 2014. 25,713724.Yasushi Matsuzawa and Amir Lerman；Endothelial

21、 dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coronary Artery Disease 2014, 25:713724Swirski, S.F.K.,Nahrendorf,M.N., Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure.Science 2013. 339,161166.P Duewell et al. Nature 464, 1357-1361 (2010) doi:10.1038/nature08938ReferencesSteffen U. Eisenhardt a,b,*,1, Julia Starke a,1, Jan，et al. Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDLemonocyte interact