Platelet HIF-2 α promotes thrombogenicity through PAI-1 synthesis and extracellular vesicle release.

We report here that, hypoxia-inducible factor (HIF)-2α is translated from pre-existing mRNAs and stabilized against proteolytic degradation in enucleate platelets exposed to hypoxia. Hypoxic stress, too, stimulates platelets to synthesize plasminogen-activator inhibitor (PAI)-1 and shed extracellular vesicles, both of which potentially contribute to pro-thrombotic phenotype associated with hypoxia. Stabilization of HIF-α by administering hypoxia-mimetics into mice accelerates thrombus formation in mesenteric arterioles. In agreement, platelets from patients with chronic obstructive pulmonary disease and high altitude residents exhibiting thrombogenic attributes have abundant expression of HIF-2α and PAI-1. Thus, targeting platelet hypoxia signaling could be an effective anti-thrombotic strategy.
PMID: 31004026 [PubMed - as supplied by publisher]

Source: Haematologica - April 18, 2019 Category: Hematology Authors: Chaurasia SN, Kushwaha G, Kulkarni PP, Mallick RL, Latheef NA, Mishra JK, Dash D Tags: Haematologica Source Type: research