Proteins Involved in Platelet Signaling Are Differentially Regulated in Acute Coronary Syndrome: A Proteomic Study

Abstract

BackgroundPlatelets 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.Methodology/Principal FindingsWe 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/SignificanceThe 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.

Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches

“…We have recently analyzed the proteome of platelets from ACS patients1516, with special emphasis in STEMI, leading to the identification of a series of signaling proteins altered in the acute event. Several of these proteins are involved in integrin and GPVI signaling.…”

Platelet mRNA

“…SPARC protein has also been detected in platelet microparticles and its intracellular expression is significantly downregulated in platelets isolated from patients with non-ST segment elevation acute coronary syndrome [30,31]. …”

Combining patient proteomics and in vitro cardiomyocyte phenotype testing to identify potential mediators of heart failure with preserved ejection fraction

“…We sought to compare the platelet proteome among subjects with HFpEF in the uncompensated (hospitalized) state, compensated (outpatient) state, and controls combined with validation in plasma samples from an external cohort and bioactivity studies using human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. We hypothesized that [ 1 ] platelet proteomic analysis would successfully identify a protein associated with HFpEF, and [ 2 ] human iPSC-derived cardiomyocytes treated with recombinant proteins could serve as further validation by demonstrating phenotypic changes in cardiomyocyte calcium handling, which is altered in HFpEF.…”