Increased platelet binding to circulating monocytes in acute coronary syndromes

Abstract

Background - Present therapies for acute coronary syndromes aim toward limiting platelet-platelet adhesion and aggregation processes. However, platelet-leukocyte interactions may contribute importantly to disease progression in the arterial wall. Recent studies suggest that prevention of platelet-leukocyte binding via P-selectin glycoprotein ligand-1 (PSGL-1) may be beneficial in animal models of vascular injury. Methods and Results - P-selectin-PSGL-1 interactions were found to account for most platelet-monocyte binding observed in peripheral blood samples from healthy donors. However, a significant component of observed adhesion was calcium independent, involving neither PSGL-1 nor P-selectin. Platelet-monocyte interactions were examined in 52 patients admitted within 14 hours of symptom onset, with acute coronary syndromes defined as unstable angina (n = 12) and acute myocardial infarction (n = 13) or noncardiac chest pain (n = 27). When compared with patients with noncardiac chest pain, significantly elevated levels of platelet-monocyte binding were found in patients with acute myocardial infarction (70.1±15.4% versus 45.4±23.3%, P<0.01) and unstable angina (67.4±12.9% versus 45.4±23.3%; P>0.01). Calcium-independent platelet-monocyte binding was significantly elevated in myocardial infarction patients alone (14.7±7.7% versus 6.1±5.96%; P<0.001). Conclusions - There is evidence for a significant P-selectin-independent molecular component to the platelet-monocyte conjugation observed in peripheral blood. Patients with myocardial infarction and unstable angina demonstrate increased total binding of platelets to monocytes. Additionally, calcium-independent adhesion was significantly elevated in patients with evidence of myocardial infarction. These findings demonstrate that novel cation-independent adhesion mechanisms may mediate platelet-monocyte binding, representing a new therapeutic target after vascular injury associated with myocardial infarction.