Proteins involved in platelet signaling are differentially regulated in acute coronary syndrome: a proteomic study.
BACKGROUND
Platelets play a fundamental role in pathological events underlying acute coronary syndrome (ACS). Because platelets do not have a nucleus, proteomics constitutes an optimal approach to follow platelet molecular events associated with the onset of the acute episode.


RESULTS
We performed the first high-resolution two-dimensional gel electrophoresis-based proteome analysis of circulating platelets from patients with non-ST segment elevation ACS (NSTE-ACS). Proteins were identified by mass spectrometry and validations were by western blotting. Forty protein features (corresponding to 22 unique genes) were found to be differentially regulated between NSTE-ACS patients and matched controls with chronic ischemic cardiopathy. The number of differences decreased at day 5 (28) and 6 months after the acute event (5). Interestingly, a systems biology approach demonstrated that 16 of the 22 differentially regulated proteins identified are interconnected as part of a common network related to cell assembly and organization and cell morphology, processes very related to platelet activation. Indeed, 14 of those proteins are either signaling or cytoskeletal, and nine of them are known to participate in platelet activation by αIIbβ3 and/or GPVI receptors. Several of the proteins identified participate in platelet activation through post-translational modifications, as shown here for ILK, Src and Talin. Interestingly, the platelet-secreted glycoprotein SPARC was down-regulated in NSTE-ACS patients compared to stable controls, which is consistent with a secretion process from activated platelets.


CONCLUSIONS
The present study provides novel information on platelet proteome changes associated with platelet activation in NSTE-ACS, highlighting the presence of proteins involved in platelet signaling. This investigation paves the way for future studies in the search for novel platelet-related biomarkers and drug targets in ACS.
Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Andrés Fernández
AF
Parguiña
Andrés
A
Fernández Parguiña
Lilian
L
Grigorian-Shamajian
Rosa M
RM
Agra
Elvis
E
Teijeira-Fernández
Isaac
I
Rosa
Jana
J
Alonso
Juan E
JE
Viñuela-Roldán
Ana
A
Seoane
José Ramón
JR
González-Juanatey
Angel
A
García
D054058:Acute Coronary Syndrome / Q000378:metabolism*; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015539:Platelet Activation; D040901:Proteomics; D015398:Signal Transduction; D049490:Systems Biology
D001798:Blood Proteins