Proteome Research In Carotid Atherosclerotic Plaques

Objectives: Atherosclerosis is that lipid accumulation, fibrous matrixformation and cell migration occur in the large or middle arterial wall undermultiple risk factors, forming atherosclerotic lesions. This disease is a chronicprogressive disease, which is characterized by involvement of the arterialintima from the beginning, there have been a variety of diseases combined.Early fatty streaks are formed by cholesterol, lipids and foam cells containinglipid droplets,and may appeared in youth; Then slowly fibrous tissues occurr,surrounding the lipid core, and the middle artery structure graduallydegenerate into fibrous plaque, making the arterial wall thickening andluminal narrowing, easy to cause tissue ischemia; Lipid pool and necrotic corefurther increase,and become into atherosclerotic plaque, prone to plaquerupture, plaque hemorrhage and local thrombosis, often causing acutecardiovascular and cerebrovascular events. The pathogenesis of this disease iscomplex,there were doctrines of lipid infiltration, thrombosis and smoothmuscle cell cloning, to illustrate the disease from different aspects. In recentyears, many studies support the doctrines of " endothelial injury" and"inflammation hypothesis." Consider a variety of risk factors for the diseaseeventually lead to arterial intimal injury,and the formation of atheroscleroticlesions is that arterial inflammation–fibrosis response to the arterial intimalinjury. If we know the protein expressed in the unstable atheroscleroticplaques,it is important for us to understand the pathogenesis of plaque rupture,plaque hemorrhage and local thrombosis in unstable plaques, from theperspective of molecular, causing acute clinical ischemic events,as well as tofind new clinical treatments to stable plaques.Proteomics include all proteins a cell or an organism expressed.This is essentially a large-scale study of the level of the basic properties of the protein,including the protein expression, translation, modification and the interactionbetween proteins, thereby to obtain an overall understanding of thedevelopment of disease on the protein level.In this study, by proteomics technologies we study carotid atheroscleroticplaques.Through the identification of the total protein,we study the changes ofprotein expression in disease, finding the disease-related protein, and furtherunderstanding of the pathogenesis.Methods: Carotid atherosclerotic plaques were obtained from the patientswho undergo carotid endarterectomy in the Second Hospital of Hebei MedicalUniversity from March2010to November2012.Plaques frozen at-80℃.Plaques will be divided into two groups, stable group and unstable group,based on AHA classification. Extract total protein by running SDS-PAGE,thenstain with Coomassie Brilliant Blue G250. After bleaching with ddH2O,digestthe1-D protein bands in-gel.With LC-LTQ-MS/MS and database search, wecan identify and analyze protein function.Results:1. According to AHA and patients,carotid ultrasound findingsand clinical presentation,we get14cases of unstable plaques.2.14cases ofunstable plaques identified204protein.3. We identified protein involved instress response, inflammation, oxidation, apoptosis, proteolysis, bloodcoagulation and other biological processes as well as protein involved in thecomplement and coagulation cascades, regulation of actin cytoskeleton,digestion and absorption of protein, glycolysis/gluconeogenesis and othersignaling pathways.Conclusion: we have identified a number of protein, which may beinvolved in stress, inflammation, apoptosis and oxidation inatherosclerosis.This will help us to comprehense the pathological mechanismsof atherosclerosis at the protein level.