Plasma Phospholipid Transfer Protein Promotes Platelet Aggregation.

Area of Science:

• Cardiovascular Biology
• Hemostasis and Thrombosis
• Lipid Metabolism

Background:

• The role of plasma phospholipid transfer protein (PLTP) in coagulation states (hyper-coagulation or hypo-coagulation) is not fully understood.
• Investigating PLTP's direct impact on platelet function is crucial for understanding its contribution to thrombosis.

Purpose of the Study:

• To elucidate the direct effect of PLTP on platelet aggregation and its underlying mechanisms.
• To determine if PLTP influences phosphatidylserine externalization and thrombosis in vivo.

Main Methods:

• Isolated human and mouse platelets, mouse platelet-rich plasma, and human recombinant PLTP.
• Assessed platelet aggregation (ADP, collagen, thrombin-induced), phosphatidylserine externalization, and photothrombosis-induced cerebral infarction in mice.
• Utilized PLTP-overexpressing and deficient mouse models.

Main Results:

• PLTP is present in human platelets and enhances platelet aggregation.
• PLTP over-expression increased platelet aggregation and phosphatidylserine externalization, while deficiency reduced these effects.
• PLTP promoted thrombosis in vivo, evidenced by accelerated cerebral infarction in transgenic mice and reduced infarction in deficient mice.

Conclusions:

• PLTP promotes phosphatidylserine externalization on platelet plasma membranes, enhancing platelet aggregation.
• PLTP plays a significant role in initiating thrombin generation and platelet aggregation under shear stress, indicating its involvement in hyper-coagulation.
• Inhibiting PLTP presents a potential therapeutic strategy for managing thrombotic disorders.