MALAT1 promotes platelet activity and thrombus formation through PI3k/Akt/GSK-3β signalling pathway.

Abstract

Background: Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis, which rely on platelet activity. In platelets, a wide variety of microRNAs (long non-coding RNA, lncRNAs) is found. Due to the absence of nuclear DNA in platelets, lncRNAs may serve as critical post-transcriptional regulators of platelet activities. However, research into the roles of lncRNAs in platelets is limited.

Objective: The purpose of this study is to learn more about the molecular mechanism by which MALAT1 affects platelet activity and thrombus formation.

Methods/results: The CD34⁺ megakaryocytes used in this research as an in vitro model for human megakaryocytes and platelets. Cell adhesion and spreading are enhanced in the absence and presence of agonists in CD34⁺ megakaryocytes subjected to MALAT1 knockdown (KD). The adhesion and activity of platelet-like particles produced by MALAT1 KD cells are significantly enhanced at rest and after thrombin activation. Thrombus development on a collagen matrix is also greatly enhanced in the microfluidic whole-blood perfusion model: platelets lacking MALAT1 exhibit elevated accumulation, distributing area and activity. In addition, MALAT1-deficient mice bleed less and form a stable occlusive thrombus more quickly than wild-type mice. PTEN and PDK1 regulated the activity of MALAT1 in platelets to carry out its PI3k/Akt/GSK-3β signalling pathway-related function.

Conclusion: The suppression of MALAT1 expression significantly increases platelet adhesion, spreading, platelet activity, and thrombus formation. lncRNAs may constitute a unique class of platelet function modulators.