Complement activation and atherosclerosis.
Atherosclerosis is an inflammatory disease mediated through the action of monocyte/macrophages, complement and T-lymphocytes. C5a and monocyte chemotactic factor released during complement activation in the arterial wall may participate in the initial monocyte recruitment. Assembly of C5b-9 on cells of the arterial wall may also induce cell lysis. On the other hand, sublytic assembly of C5b-9 on smooth muscle cells (SMC) and endothelial cells (EC) induces cell activation and proliferation. Analysis of mitogen activated protein kinases (MAPK) pathways induced by C5b-9 in aortic SMC revealed that extracellular signal regulated kinase (ERK) 1, c-jun NH2-terminal kinase (JNK) 1, and p38 MAPK are all activated by C5b-9. ERK1 activity was inhibited by wortmannin suggesting that ERK1 pathway is activated through phosphatidyl inositol -3 (PI 3-) kinase. Sublytic C5b-9 assembly on the plasma membrane was also able to activate Janus kinase (JAK) 1, signal transducer and activator (STAT) 3 and STAT4 in EC. JAK1 but not STAT3 activation induced by C5b-9 is dependent on Gi protein activation. New evidence accumulated during the last decade support the role of complement activation in both initiation and progression of the atherosclerotic lesions. Complement system activation is a major component of the chronic inflammatory process associated with atherosclerosis.
Niculescu
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Department of Pathology, University of Maryland, School of Medicine, Baltimore 21201, USA. fnicules@umaryland.edu
Rus
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D000818:Animals; D001158:Arteries / Q000276:immunology; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000378:metabolism / Q000494:pharmacology; D003165:Complement System Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction
D015938:Complement Membrane Attack Complex; D007136:Immunoglobulins; D003165:Complement System Proteins