Platelet Activation in Cardiovascular Disease

Abstract 5242

Platelets play a pivotal role in the pathogenesis of coronary artery disease (CAD). Among a number of platelet integrin receptors ITGA2B and ITGB3 appear to be fundamental mediators of platelet aggregation as they interact with fibrinogen, VWF, fibronectin, vitronectin, and thrombospondin; for these major properties these two receptors are risk-determining factors for increased platelet thrombogenicity, enhancement of leukocytes trafficking and activation by CD11a/CD18 (LFA-1) and CD11b/CD18 (MAC-1), thus leading to CAD.

Receptor clustering promote cell adhesion by increasing the number of ligand receptor bonds GPIb-IX-VWF, fibrinogen /alfaIIb-beta 3 which promote platelet aggregation; this is showed by various parameters including increased platelet-monocyte aggregates, P-selectin (CD62P), CD42b, CD63, and EMMPRIN (CD147). The link between platelet activation, leukocyte recruitment, endothelial dysfunction, progression of atherosclerosis plaque and CAD has been demonstrated through the involvement of inflammatory cytokines that play a central role in the development of atherosclerotic plaques with MCP-1, CCL-2, Rantes, IL-8, and CD40L.

In this study, we investigated a total of 38 subjects (mean age of 62 +/− 6 years) with confirmed CAD (unstable angina: 18 patients; ST elevation myocardial infarction: 20 patients) on coronary angiography and 32 controls. They were examined for CD62P, CD63, CD42b, and CD147 expression, troponin level, creatine-kinase-MB level (indicator of myocardial injury), C-reactive protein, and IL-6 (being both indicators of systemic inflammation).

Patients with CAD had significantly higher markers of platelet activation (p<0.001) which were constituted by the expression of GP receptors (CD62P/PSGL-1, CD162, CD61/63, CD147). This activity closely correlates with a significant increase of acute phase reactant in cases than in controls (p<0.0001), and mostly, it confirmed that these associations may be largely responsible of cardiovascular events.