New pathogenetic mechanisms in acute coronary syndrome: the role of platelet-associated Tissue Factor
Tissue Factor is a 47kD glycoprotein which triggers the blood coagulation cascade. Its expression within the atherosclerotic plaque directly correlates with the plaque thrombogenicity. We previously described the presence of TF in human platelets and we showed that this glycoprotein is expressed under the control of both platelet agonists and some antiplatelet drugs.
More recently we provided the evidence that TF expression is significantly higher in resting platelets of patients with ACS compared to patients with SA. This results in a greater capacity of platelets to generate thrombin, which in turn contributes to the prothrombotic phenotype of ACS patients.
New pathogenetic mechanisms in acute coronary syndrome: platelet transcriptomic and proteomic analysis
Although platelets do not have a nucleus, they contain more than 2000 megakaryocyte-derived mRNAs, which may influence pathophysiological functions. Comparing the platelet transcriptome of SA and NSTE-ACS patients we identified 45 differentially expressed genes involved in signal transduction, macromolecular complex assembly, and response to stress that may modulate platelet reactivity in CAD.
The analysis of the platelet proteome in SA and NSTE-ACS patients identified differential expression in proteins, not previously connected with CAD, such as energy metabolism enzymes, and proteins associated with cytoskeleton-based processes, both of which indicate platelet activation
Predictive value of circulating microparticle signature in coronary bypass graft patency
Cell-derived microparticles (MPs) are emerging as novel players in cardiovascular disease (CVD). They are involved in intercellular communication being vectors of biological messages, including nucleic acids (mRNA and microRNA [miRNA]), that participate in the pathophysiology and development of disease.
Circulating MPs have been considered as biomarkers of vascular injury and inflammation in several CVD including atherothrombosis and myocardial infarction where elevated levels of MPs have been correlated with the severity of pathology. Recently, also miRNAs have been shown to play a key role in CVD opening the possibility to use them as diagnostic surrogate markers. Graft patency and completeness of revascularization are major determinants of long-term outcome after coronary artery bypass grafting (CABG). Occlusion rates can be as high as 28% (per graft) or 45% (per patient) 12- 18 months thereafter. Endothelial damage, inflammation, and intimal hyperplasia are among the main candidates responsible for the early, and possibly late, graft failure.
The issue of identifying predictors of graft patency after CABG has been addressed by several studies, which mainly focused on the presence of conventional risk factors, genetic markers, features of coronary targets, or technical aspects. Fewer studies have focused on biological markers, such as perioperative inflammatory factors, but none has assessed the potential involvement of MPs and endogenous miRNAs. To this end we are elucidating whether a specific “signature” of circulating MPs is associated with postoperative CV adverse events, e.g., bypass graft occlusion, in patients undergoing elective surgical myocardial revascularization.
