Phosphoinositide 3-Kinases as Potential Targets for Thrombosis Prevention

Int J Mol Sci. 2022 Apr 27;23(9):4840. doi: 10.3390/ijms23094840.

Abstract

As integral parts of pathological arterial thrombi, platelets are the targets of pharmacological regimens designed to treat and prevent thrombosis. A detailed understanding of platelet biology and function is thus key to design treatments that prevent thrombotic cardiovascular disease without significant disruption of the haemostatic balance. Phosphoinositide 3-kinases (PI3Ks) are a group of lipid kinases critical to various aspects of platelet biology. There are eight PI3K isoforms, grouped into three classes. Our understanding of PI3K biology has recently progressed with the targeting of specific isoforms emerging as an attractive therapeutic strategy in various human diseases, including for thrombosis. This review will focus on the role of PI3K subtypes in platelet function and subsequent thrombus formation. Understanding the mechanisms by which platelet function is regulated by the various PI3Ks edges us closer toward targeting specific PI3K isoforms for anti-thrombotic therapy.

Keywords: PI3K; antiplatelet therapy; phosphoinositide 3-kinase; platelets; thrombosis.

Publication types

  • Review

MeSH terms

  • Blood Platelets / pathology
  • Humans
  • Phosphatidylinositol 3-Kinases*
  • Phosphatidylinositols
  • Protein Isoforms
  • Thrombosis* / drug therapy
  • Thrombosis* / pathology
  • Thrombosis* / prevention & control

Substances

  • Phosphatidylinositols
  • Protein Isoforms

Grants and funding

This work was supported by the National Health Medical Research Council of Australia (NHMRC) via grants to J.R.H. (Project grant numbers 1137508 and 1187595).