GALECTINS NOVEL REGULATORS OF PLATELET SIGNALING AND FUNCTION: THERAPEUTIC IMPLICATIONS

RABINOVICH GABRIEL; SCHATTNER MIRTA

Galectins and Disease Implications for Targeted Therapeutics

ACS Series Books

Año: 2013; p. 95 - 106

Platelets are enucleated blood cells derived from megakaryocytes that are essential for proper hemostasis and thrombosis and also play critical roles in inflammatory processes, atherosclerosis, tumor metastasis and host defense. When platelets perceive activating signals through their cell surface receptors, they undergo dramatic structural and chemical changes, involving a complex interplay of cell adhesion and signaling molecules. Activated platelets rapidly bind circulating platelets via membrane integrin αIIbβ3 (GPIIb/IIIa) and fibrinogen, to form a thrombus for preventing bleeding at sites of vascular injury. However, platelet aggregation can also occlude atherosclerotic arteries causing cardiac and cerebrovascular diseases(1). Galectins are structurally related carbohydrate-binding proteins, which are defined by their affinity for poly-N-acetyllactosamine-enriched glycoconjugates and sequence similarities in the carbohydrate recognition domain (CRD) (2). Although experimental and clinical studies have extensively implicated galectins in the regulation of immune cell homeostasis and host-pathogens interactions, there is increasing evidence that these proteins are also involved in the pathogenesis of cardiovascular diseases, in particular development of atherosclerosis (3,4). Moreover, recent work from our laboratory has shown that galectin (Gal)-1 and Gal-8 can trigger platelet activation by interacting with different platelet receptors and promote the formation of platelet-leukocyte aggregates suggesting a novel mechanism of thrombus formation mediated by galectin-glycan interactions (5,6).