MALAT1 Promotes Platelet Activity and Thrombus Formation Through PI3k/Akt/GSK-3β Signalling Pathway

Overview

Journal Stroke Vasc Neurol

Specialty Cardiology & Vascular Diseases

Date 2022 Oct 14

PMID 36241224

Authors

Yeying Sun

Tao Wang

Yan Lv

Jiahua Li

Xiaoli Jiang

Jing Jiang

Daolai Zhang

Weihua Bian

Chunxiang Zhang

Affiliations

Soon will be listed here.

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.

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