Ablation of CD38 Alleviates the Secondary Aggregation of Platelets.

Abstract

CD38 is an ectoenzyme that plays an essential role in mobilizing intracellular Ca²⁺. Here, we intend to demonstrate the role of CD38 in platelet primary and secondary aggregation and suggesting the need to inhibit primary aggregation for cardiovascular patients. Mouse platelets were used in this study. Platelet aggregation, in vitro thrombus formation, release reactions, and calcium signalling experiments were performed in response to thrombin, a normal agonist of platelets. For aggregation, pathway-specific inhibitors were used to differentiate between primary and secondary aggregation. In an in vitro setting, the formation of a thrombus revealed a distinctive pattern on the collagen-coated surface when comparing two types of platelets. Platelets positive for CD38 exhibited smaller yet more aggregated platelets than CD38-negative platelets. Moreover, in vitro, the aggregation process exhibited distinct patterns for the two types of platelets. By employing various inhibitors, we were able to distinguish between the primary and secondary aggregation pathways, both upstream and downstream. The release reaction and calcium signalling were valuable for identifying primary and secondary aggregation events based on their respective time frames. Distinct variations in thrombus formation and aggregation patterns suggest the involvement of CD38. The significant difference in the second minute of calcium signalling and release reaction evidently established a distinct time interphase between primary and secondary aggregation.