Apolipoprotein A-I, elevated in trauma patients, inhibits platelet activation and decreases clot strength

Wilbert L. Jones, Christopher R. Ramos, Anirban Banerjee, Ernest E. Moore, Kirk C. Hansen, Julia R. Coleman, Marguerite Kelher, Keith B. Neeves, Christopher C. Silliman, Jorge Di Paola, Brian Branchford

Research output: Contribution to journalArticlepeer-review

Abstract

Apolipoprotein A-I (ApoA-I) is elevated in the plasma of a subgroup of trauma patients with systemic hyperfibrinolysis. We hypothesize that apoA-I inhibits platelet activation and clot formation. The effects of apoA-I on human platelet activation and clot formation were assessed by whole blood thrombelastography (TEG), platelet aggregometry, P-selectin surface expression, microfluidic adhesion, and Akt phosphorylation. Mouse models of carotid artery thrombosis and pulmonary embolism were used to assess the effects of apoA-I in vivo. The ApoA-1 receptor was investigated with transgenic mice knockouts (KO) for the scavenger receptor class B member 1 (SR-BI). Compared to controls, exogenous human apoA-I inhibited arachidonic acid and collagen-mediated human and mouse platelet aggregation, decreased P-selectin surface expression and Akt activation, resulting in diminished clot strength and increased clot lysis by TEG. ApoA-I also decreased platelet aggregate size formed on a collagen surface under flow. In vivo, apoA-I delayed vessel occlusion in an arterial thrombosis model and conferred a survival advantage in a pulmonary embolism model. SR-BI KO mice significantly reduced apoA-I inhibition of platelet aggregation versus wild-type platelets. Exogenous human apoA-I inhibits platelet activation, decreases clot strength and stability, and protects mice from arterial and venous thrombosis via the SR-BI receptor.

Original languageEnglish
Pages (from-to)1119-1131
Number of pages13
JournalPlatelets
Volume33
Issue number8
DOIs
StatePublished - 2022

Keywords

  • Hyperfibrinolysis
  • SR-B1 receptor
  • microfluidics
  • platelet inhibition
  • thrombelastography

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