Abstract
Platelet hyperreactivity, defined as enhanced sensitivity to activation in response to classical agonists, contributes to the increased risk of arterial thrombosis associated with chronic inflammatory diseases. In this issue of the JCI, Kong and colleagues used an unbiased proteomic approach to identify elevated SEC61B in platelets from patients with diabetes and from hyperglycemic mice. Typically, SEC61B participates in protein transport within the endoplasmic reticulum (ER), but it can also act as an ion channel that allows calcium to leak from ER to cytoplasm. The authors showed that elevated SEC61B expression caused increased calcium leak, elevated basal cytoplasmic calcium concentrations, and platelet hyperreactivity. In vitro and in vivo pharmacological interventions to alter calcium homeostasis through this pathway affected platelet reactivity. The results of this work are consistent with those of previous studies showing that platelets from patients with chronic diseases behaved differently than those from healthy participants. These findings identify potential disease-specific targets to prevent and treat arterial thrombosis.