A proteomic focus on the alterations occurring at the human atherosclerotic coronary intima.
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.
Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
Fernando
F
de la Cuesta
Gloria
G
Alvarez-Llamas
Aroa S
AS
Maroto
Alicia
A
Donado
Irene
I
Zubiri
Maria
M
Posada
Luis R
LR
Padial
Angel G
AG
Pinto
Maria G
MG
Barderas
Fernando
F
Vivanco
D017314:Annexin A4 / Q000378:metabolism; D001052:Apoferritins / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D025341:Principal Component Analysis; D020543:Proteome / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods; D014746:Vimentin / Q000378:metabolism
D017314:Annexin A4; D055551:HSP27 Heat-Shock Proteins; D006454:Hemoglobins; D018994:Myosin Light Chains; D020543:Proteome; D014746:Vimentin; D001052:Apoferritins
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