Connexin 37 Counteracts Clotting

Abstract

The thrombotic response elicited by arterial injury or atherosclerosis varies widely between individuals; in some, diffuse coronary artery disease never triggers thrombotic occlusion, whereas others with limited disease experience myocardial infarction (MI) due to arterial thrombosis. Understanding the predictors for arterial thrombosis will improve tailored therapy for preventing and treating the complications of atherosclerosis and vascular injury. Extensive effort has been invested in developing accurate tools for risk stratification based on clinical features, but interactions between genetic and environmental factors will also influence an individual's risk for thrombosis. We are only beginning to appreciate how genetic factors may have an impact on the function of platelets, which play a key role in arterial thrombosis by forming an initial plug at sites of arterial injury or atherosclerotic plaque rupture or erosion. Ex vivo assays of platelet function reveal substantial interindividual heterogeneity, suggesting the hypothesis that intrinsic platelet reactivity may predict propensity to thrombosis. In animal models, the targeted deletion of any one of a number of proteins involved in platelet activation and/or aggregation protects from experimental thrombosis. Likewise, in the case of pharmacologically targeting P2Y12 receptors, more potent antagonists reduce clinical outcomes such as acute stent thrombosis. However, whether heightened platelet reactivity, in the absence of antiplatelet therapy, is causally associated with arterial thrombosis remains unknown. This is due, in part, to a lack of understanding of the pathways that may normally check platelet activation. In the current issue of Circulation , Angelillo-Scherrer et al 1 add connexin 37 (Cx37) to the small, but growing, list on membrane proteins that negatively regulate platelet function and implicate the Cx37 genotype as a risk marker for thrombosis. Article see p 930 The findings of Angelillo-Scherrer et al are important for …