A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima

Abstract

Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. Molecular & Cellular

Molecular anatomy of ascending aorta in atherosclerosis by MS Imaging: Specific lipid and protein patterns reflect pathology

“…Tissue samples were obtained from 10 subjects (male:7 , average age: 76 ) with atherosclerotic lesions previously characterized [28] which show a well formed lipid core, presence of an inflammatory infiltrate, and evidence of sporadic calcification. Control arteries were obtained from 4 individuals who did not die from cardiovascular events and with no evidences of atherosclerotic lesions in any of the most frequently affected arteries (male: 2, average age: 48).…”

Contribution of proteomics to the management of vascular disorders

“…It is this latter group of proteins that is of potential interest for biomarker discovery, as they may reflect the physiological state of a specific cell population or tissue. Tissue proteomics in the context of atherothrombosis has allowed the atherosclerotic plaque [40][41][42][43], and the thrombus [44] to be characterized in greater depth. In comparison to blood, which may constitute an intermediary between organs and physiological activity, tissue proteome analysis is more directly linked to specific pathological states.…”

“…Nevertheless, in our experience coupling of LMD and proteomic analysis is now feasible due to the enhanced sensitivity of mass spectrometers and the appearance of fluorescent labeling dyes for two-dimensional electrophoresis (2-DE, e.g., saturation labeling DIGE [46,47]). Indeed, this has allowed us to perform differential layer-specific analysis of protein abundance in the atherosclerotic human coronary artery [41,42].…”

Proteomics and Metabolomics in Aortic Stenosis: Studying Healthy Valves for a Better Understanding of the Disease

“…The main disadvantage of this methodology in combination with proteomics is the scarce amount of protein that can be obtain, since the laser cannot be applied for a long time in order to avoid protein degradation. However, mass spectrometers have exponentially improved their sensitivity, so there are several interesting studies combining LMD and Proteomics in other cardiovascular tissues samples [17][18][19][20]. The application of LMD to the analysis of the AV tissue could provide specific data from the different layers/structures in the tissue, as well as from the behavior of the different cells in the tissue.…”