2D-DIGE-based proteomic analysis of intracoronary versus peripheral arterial blood platelets from acute myocardial infarction patients: Upregulation of platelet activation biomarkers at the culprit site

Proteomics Clin Appl. 2016 Aug;10(8):851-8. doi: 10.1002/prca.201500120. Epub 2016 May 23.

Abstract

Purpose: Platelets play a fundamental role in the atherothrombotic events that lead to an acute myocardial infarction. In the present study we compared the proteome of intracoronary and peripheral arterial platelets from ST-elevation myocardial infarction (STEMI) patients in the search for potential platelet biomarkers/drug targets related to what is happening at the culprit site.

Experimental design: Ten STEMI patients were recruited and blood collected from the occluded coronary artery, at the culprit site, in the moment of reperfusion. Systemic blood obtained from the radial artery of the same patients was used as control. Proteome analysis was based on high-resolution 2D-DIGE and mass spectrometry. Validations were by western blotting in a group of 11 patients.

Results: Sixteen differentially regulated protein features were identified, corresponding to 15 ORFs, mostly related to cytoskeletal and signaling proteins. We demonstrate the up-regulation of integrin αIIb (ITA2B), the adapter Src kinase-associated phosphoprotein-2 (SKAP2), and thrombospondin-1 isoforms in intracoronary platelets.

Conclusion and clinical relevance: This study constitutes the first analyzing in detail the proteome of arterial intracoronary platelets from STEMI patients. We show variations in the platelet proteome when comparing intracoronary and peripheral platelets. Observed differences might be related to platelet activation events at the culprit site.

Keywords: Acute myocardial infarction; Integrin αIIb; Intracoronary; Platelet proteome; SKAP-2; Thrombospondin-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Artifacts
  • Blood Platelets / metabolism*
  • Blood Platelets / physiology
  • Coronary Vessels / pathology*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Myocardial Infarction / blood*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Platelet Activation*
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Proteomics / methods*
  • Talin / metabolism
  • Thrombospondin 1 / metabolism
  • Two-Dimensional Difference Gel Electrophoresis*
  • Up-Regulation*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Platelet Membrane Glycoprotein IIb
  • TLN1 protein, human
  • Talin
  • Thrombospondin 1
  • src kinase associated phosphoprotein 2