Coronary artery bypass graft surgery up-regulates genes involved in platelet aggregation

J Thromb Haemost. 2012 Apr;10(4):557-63. doi: 10.1111/j.1538-7836.2012.04660.x.

Abstract

Background: During and shortly after coronary artery bypass graft (CABG) surgery, there is an increase in thromboembolic events. CABG, a strong inflammatory stimulus, is associated with a hypercoaguable state. Platelets might contribute to this hypercoaguable state because they have a pivotal role in thrombosis. In the days following surgery there is augmented platelet regeneration in response to the inflammatory stimulus.

Objectives: The aim of this study was to investigate any changes in platelet mRNA profiles to test the hypothesis that post-CABG surgery platelets are associated with a prothrombotic state.

Methods: Blood was sampled and platelets purified from 11 patients before and 3-6 days after CABG. Gene expression profiling was performed using low density array (LDA) plates for seven of the patients.

Results: Forty-five genes were examined and those significantly up-regulated were glycoprotein (GP)IIb, GPIIIa and cyclooxygenase-1 (COX-1). These findings were confirmed in four more patients, including flow cytometry analysis of the GPIIb/IIIa receptor.

Conclusions: CABG surgery up-regulates mRNA and protein levels of proteins that are key players in platelet aggregation. Marked elevation of GPIIb/IIIa mRNA levels results in significantly increased GPIIb/IIIa expression in platelets post-CABG surgery, which may be a reason for increased thrombus formation and myocardial infarction after CABG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Platelets / metabolism*
  • Coronary Artery Bypass / adverse effects*
  • Cyclooxygenase 1 / genetics
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Integrin alpha2 / genetics
  • Integrin beta3 / genetics
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / etiology
  • Myocardial Infarction / genetics
  • Platelet Aggregation / genetics*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • RNA, Messenger / blood
  • Risk Assessment
  • Risk Factors
  • Sweden
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / genetics*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • ITGA2B protein, human
  • ITGB3 protein, human
  • Integrin alpha2
  • Integrin beta3
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • RNA, Messenger
  • Cyclooxygenase 1
  • PTGS1 protein, human