Abstract 351: Plasma Phospholipid Transfer Protein Promotes Platelet Aggregation

Abstract

Hypothesis: Phospholipid transfer protein (PLTP) has a direct effect on platelet aggregation, since PLTP knockout mice have longer bleeding time. Methods and Results: Platelets from humans or mice were prepared as were mouse platelet-rich plasma and human recombinant PLTP (rPLTP). In mice, we assessed ADP- and collagen-induced platelet aggregation, phosphatidylserine (PS) externalization, and photothrombosis-induced cerebral infarction. We found that human platelets produce PLTP. Platelet aggregation increased upon PLTP overexpression whereas it decreased with PLTP deficiency in a gene dose-dependent manner. Human rPLTP increased mouse or human platelet aggregation in a dose-dependent manner. PS externalization provides a water/lipid surface for the interaction of coagulation factors, which accelerates thrombosis. Compared with wild type controls, platelets from PLTP transgenic mice had significantly greater amounts of PS on the exterior surface of the plasma membrane, whereas platelets from PLTP-deficient mice had significantly less on the surface, thus influencing fibrinogen binding. Moreover, rPLTP together with ADP significantly increased PS exposure on the plasma membrane of PLTP-deficient platelets, thereby increasing fibrinogen binding. Importantly, PLTP overexpression significantly accelerated the incidence of photothrombosis-induced infarction, whereas PLTP deficiency reduced the incidence. Conclusions: PLTP promotes PS externalization at the plasma membrane of platelets and accelerates ADP- or collagen-induced platelet aggregation. Thus, PLTP is involved in hypercoagulation. Therefore, PLTP inhibition could be a novel approach for countering thrombosis.