Platelet-derived CXCL12 (SDF-1α): basic mechanisms and clinical implications

Platelets are a major source of CXCL12 (stromal cell-derived factor -1, SDF-1) and store CXCL12 as part of their -granule secretome. Platelet activation enhances surface expression and release of CXCL12. Platelets and megakaryocytes express CXCR4, the major receptor for CXCL12, and interaction of CXCL12 with CXCR4 regulates megakaryopoiesis and the function of circulating platelets. Platelet-derived CXCL12 also modulates paracrine mechanisms such as chemotaxis, adhesion, proliferation and differentiation of nucleated cells, including progenitor cells. Platelet-derived CXCL12 enhances peripheral recruitment of progenitor cells to the sites of vascular and tissue injury both in vitro and in vivo and thereby promotes repair mechanisms. CXCL12 expression on platelets is elevated in patients with acute myocardial infarction, correlates with the number of circulating progenitor cells, is associated with preservation of myocardial function and is an independent predictor of clinical outcome. Administration of recombinant CXCL12 reduces infarct size following transient ischemia in mice. The present review summarizes the role of platelet-derived CXCL12 in cardiovascular biology and its diagnostic and therapeutic implications.