Clinical Research in Cardiology

, Volume 99, Issue 9, pp 557–564

Altered nitric oxide/cGMP platelet signaling pathway in platelets from patients with acute coronary syndromes

  • Loredana Bergandi
  • Marco Cordero
  • Matteo Anselmino
  • Gaetana Ferraro
  • Laura Ravera
  • Paola Dalmasso
  • Corrado Moiraghi
  • Gian Paolo Trevi
  • Dario Ghigo
  • Amalia Bosia
  • Serena Bergerone
Original Paper

DOI: 10.1007/s00392-010-0157-3

Cite this article as:
Bergandi, L., Cordero, M., Anselmino, M. et al. Clin Res Cardiol (2010) 99: 557. doi:10.1007/s00392-010-0157-3

Abstract

This study was aimed at evaluating whether the nitric oxide (NO)/cyclic GMP (cGMP) signaling pathway is altered in platelets from patients with an acute coronary syndrome (unstable angina and acute myocardial infarction). We investigated 10 patients with unstable angina (UA), 14 with acute myocardial infarction (AMI) and 14 age and sex-matched healthy subjects. The serum markers of platelet activation (sP-selectin), inflammation (TNF-α and erythrocyte sedimentation rate), thrombotic state (fibrinogen) and plaque disruption were significantly higher in both UA and AMI patients compared to the healthy controls. In their platelets we assessed the cGMP levels in basal conditions and after stimulation with sodium nitroprusside (SNP), and performed Western blot analysis of homogenates to measure the expression of soluble guanylate cyclase isoforms. Basal levels of cGMP (pmol/1010 platelets) were significantly higher in platelets from UA patients (1,097 ± 111; p < 0.0001) and AMI (1,122 ± 77; p < 0.0001) compared to those collected from healthy controls (497 ± 80). The platelets of AMI patients exhibited a lack of cGMP increase after SNP stimulation in comparison with UA patients. The phosphorylation of upstream (Akt1 protein kinase α and endothelial NO synthase) and downstream (vasodilator-stimulated phosphoprotein, VASP) signaling proteins of the NO/cGMP pathway was investigated: serine phosphorylation in Akt1, eNOS and VASP was enhanced in platelets from UA and AMI patients when compared to controls. Furthermore, in AMI patients the inhibitors of guanylate cyclase and cGMP-dependent protein kinase did not revert the VASP phosphorylation. These data suggest that platelets from AMI patients are more resistant to SNP stimulation, not only as cGMP production, but also in terms of VASP activation. From these ex vivo results we hypothesize that the increased inflammatory state which often accompanies patients with cardiovascular diseases might promote a platelet preactivation resulting in their reduced sensitivity to NO.

Keywords

NO/cGMP pathway  Unstable angina (UA) and acute myocardial infarction (AMI) Akt1/PKBα Endothelial NO synthase (eNOS) Vasodilator-stimulated phosphoprotein (VASP) 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Loredana Bergandi
    • 1
  • Marco Cordero
    • 2
  • Matteo Anselmino
    • 2
  • Gaetana Ferraro
    • 2
  • Laura Ravera
    • 2
  • Paola Dalmasso
    • 4
  • Corrado Moiraghi
    • 3
  • Gian Paolo Trevi
    • 2
  • Dario Ghigo
    • 1
  • Amalia Bosia
    • 1
  • Serena Bergerone
    • 2
  1. 1.Dipartimento di Genetica, Biologia e Biochimica (Sezione di Biochimica)University of TorinoTurinItaly
  2. 2.Division of Cardiology, Department of Internal MedicineUniversity of TorinoTurinItaly
  3. 3.Department of EmergencySan Giovanni Battista HospitalTurinItaly
  4. 4.Department of Public Health and MicrobiologyUniversity of TorinoTurinItaly

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