title: Local carotid atherosclerotic plaque proteins for the identification of circulating biomarkers in coronary patients.
abstract: OBJECTIVE
  To identify circulating biomarkers that originate from atherosclerotic vulnerable plaques and that could predict future cardiovascular events.
  
  
  METHODS
  After a protein enrichment step (combinatorial peptide ligand library approach), we performed a two-dimensional electrophoresis comparative analysis on human carotid plaque protein extracts (fibrotic and hemorrhagic atherosclerotic plaques). In silico analysis of the biological processes was applied on proteomic data. Luminex xMAP assays were used to quantify inflammatory components in carotid plaques. The systemic quantification of proteins originating from vulnerable plaques in blood samples from patients with stable and unstable coronary disease was evaluated.
  
  
  RESULTS
  A total of 118 proteins are differentially expressed in fibrotic and hemorrhagic plaques, and allowed the identification of three biological processes related to atherosclerosis (platelet degranulation, vascular autophagy and negative regulation of fibrinolysis). The multiplex assays revealed an increasing expression of VEGF, IL-6, IL-8, IP-10 and RANTES in hemorrhagic as compared to fibrotic plaques (p<0.05). Measurement of protein expressions in plasmas from patients with stable and unstable coronary disease identified a combination of biomarkers, including proteins of the smooth muscle cell integrity (Calponin-1), oxidative stress (DJ-1) and inflammation (IL-8), that allows the accurate classification of patients at risk (p=0.0006).
  
  
  CONCLUSIONS
  Using tissue protein enrichment technology, we validated proteins that are differentially expressed in hemorrhagic plaques as potential circulating biomarkers of coronary patients. Combinations of such circulating biomarkers could be used to stratify coronary patients.
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Eric
authors: E
authors: Malaud
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Delphine
authors: D
authors: Merle
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Dominique
authors: D
authors: Piquer
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Laurence
authors: L
authors: Molina
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Nicolas
authors: N
authors: Salvetat
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Laetitia
authors: L
authors: Rubrecht
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Emilie
authors: E
authors: Dupaty
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Pascale
authors: P
authors: Galea
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Sandra
authors: S
authors: Cobo
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Aurélie
authors: A
authors: Blanc
authors: Vascular Surgery Department, Arnaud de Villeneuve Hospital, CHU Montpellier, France.
authors: Max
authors: M
authors: Saussine
authors: Vascular Surgery Department, Arnaud de Villeneuve Hospital, CHU Montpellier, France.
authors: Charles
authors: C
authors: Marty-Ané
authors: Vascular Surgery Department, Arnaud de Villeneuve Hospital, CHU Montpellier, France.
authors: Bernard
authors: B
authors: Albat
authors: INSERM U698, Bichat Hospital, Paris, France.
authors: Olivier
authors: O
authors: Meilhac
authors: Bio-Rad Laboratories, Marnes la Coquette, France.
authors: Francois
authors: F
authors: Rieunier
authors: Bio-Rad Laboratories, Marnes la Coquette, France.
authors: Agnes
authors: A
authors: Pouzet
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Franck
authors: F
authors: Molina
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France.
authors: Daniel
authors: D
authors: Laune
authors: UMR3145 CNRS Bio-Rad, SysDiag, Montpellier, France. Electronic address: jeannette.fareh@sysdiag.cnrs.fr.
authors: Jeannette
authors: J
authors: Fareh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001798:Blood Proteins / Q000032:analysis*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000601:surgery; D018925:Chemokines / Q000097:blood; D020650:Combinatorial Chemistry Techniques; D003324:Coronary Artery Disease / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D015180:Electrophoresis, Gel, Two-Dimensional; D016894:Endarterectomy, Carotid; D005260:Female; D005355:Fibrosis; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000737:chemistry*; D012422:Rupture, Spontaneous; D013382:Subtraction Technique
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D019151:Peptide Library
keywords: Atherosclerosis; Biomarkers; Prediction; Proteomic; Vulnerable plaque