Central to this thesis are the followingeventsLipidsEndothelialinjuryRoles ofSMCproliferationMacrophage(Mp)
Central to this thesis are the following events Lipids Endothelial injury SMC proliferation Macrophage(Mφ) Roles of
Role of lipids :IncreaseendothelialpermeabilityImpairendothelialfunctionOX-LDLingested byMopform foam cellschemotactic for circulating monocytesincreasemonocyte adhesionstimulate release of growth factorschemotactic to endothelial cells (EC)smooth muscle cells (SMC)
① Role of lipids : Increase endothelial permeability Impair endothelial function OX-LDL ingested by Mφ→form foam cells chemotactic for circulating monocytes increase monocyte adhesion stimulate release of growth factors chemotactic to endothelial cells (EC) smooth muscle cells (SMC)
Role of EC injury:initiallesionMechanicalinjuryRiskSmoking,HypoxiaFactorsHyperlipidemiaHypertensionECinjuryNon-denudingEC dysfunctionEC denudingIncreasedECpermeabilityEnhanced monocyte,platelet adhesionRelease GF→SMCproliferation
② Role of EC injury: initial lesion Mechanical injury Smoking , Hypoxia Hyperlipidemia Hypertension EC injury Non-denuding EC dysfunction EC denuding Increased EC permeability Enhanced monocyte, platelet adhesion Release GF→SMC proliferation Risk Factors
Role of macrophage: key stepPlatelet , EC, Monocyte, SMCGrowth Factors (PDGF, FGF, etc)emigrationproliferationadhere-→emigrant subendothelially→ foam cellsMatrixGF-SMCT
③ Role of macrophage: key step Platelet , EC, Monocyte, SMC Growth Factors (PDGF, FGF, etc) emigration proliferation adhere→emigrant subendothelially → foam cells Matrix GF→SMC↑
4Role of SMC proliferation:GF → SMC proliferation in -emigration of media SMC to intimaPhenotype change (constrictive-→synthesis)surfaceLDLreceptorfoam cell(SMC derived)collagen,elastic fiberprotein,proteoglycansInteraction→formation ofAS plaque
④ Role of SMC proliferation: GF → SMC proliferation in → emigration of media SMC to intima Phenotype change (constrictive→synthesis) surface LDL receptor→foam cell(SMC derived) collagen , elastic fiber protein, proteoglycans Interaction→formation of AS plaque