Abstract
Background: To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. Methods: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. Results: Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold (p < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin β-chain, actin, keratin, tubulin β-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic–dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. Conclusion: This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis.
Highlights
Proteomic studies have contributed substantially to the research on the pathogenesis of cardiovascular diseases, laying the foundation for the discovery of novel molecular targets and novel biomarkers of the risk of cardiovascular diseases and their complications [1,2]
Our study demonstrated a significant increase in tubulin and microfibril-associated glycoprotein 4 (MAGP-4) content in the sample of atherosclerotic plaques at the stage of lipidosis and fibrosis compared with the sample of stable plaques at the stage of fibrosis and calcification and with the sample of unstable plaques
We demonstrated that early phases of coronary atherosclerosis at the stage of stable atherosclerotic plaques show increased amounts of cytoskeletal proteins, serum amyloid P-component (SAP), and annexin 5
Summary
Proteomic studies have contributed substantially to the research on the pathogenesis of cardiovascular diseases, laying the foundation for the discovery of novel molecular targets and novel biomarkers of the risk of cardiovascular diseases and their complications [1,2]. By mass-spectrometric analysis, Herrington et al have investigated the human arterial proteome and proteomic features They uncovered substantial differences in the prevalence of a mitochondrial protein, tumor necrosis factor α, insulin receptor, and PPAR-α and -γ between coronary and aortic samples and between atherosclerotic and healthy tissues [4]. Lepedda et al have applied proteomic analysis to atherosclerotic plaque homogenates that were obtained during endarterectomy in patients with atherosclerosis of the carotid arteries. These authors detected 33 proteins differentially expressed in stable and unstable plaques. Methods: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased
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