Laboratory of Thrombosis and Hemostasis led by Prof. Hu Hu at the Zhejiang University School of Medicine recently has published online in the journal Haematologica an article entitled “Critical role of peroxisome proliferator-activated receptor α in promoting platelet hyperreactivity and thrombosis under hyperlipidemia.”. 2021 DOI: 10.3324 / haematol. 2021.279770. This study elucidated the role of PPARα in platelet activation and thrombosis under healthy condition and hyperlipidemia.

Hyperlipidemia is an established risk factor for atherothrombotic disease. Yet how hyperlipidemia is responsible for thrombosis remains unclear. Transcription factor PPARα (peroxisome proliferator-activated receptor alpha) is a known regulator key for lipid metabolism. The current study established that PPARα-supported platelet activation is critical to hyperlipidemia promoted prothrombotic condition. It is revealed that megakaryocytes, the precursor cells of platelets, respond to hyperlipidemia with an upregulation of PPARα, which bestows the platelets an enhanced ability to conduct signaling that culminates in an increased granule secretion and thrombosis. The mechanistic findings are obtained first in a hyperlipidemic mice model and recapitulated in human hyperlipidemic patients, which signifies the potential of the current study in contributing possible therapeutic targets to prevent thrombotic events associated with hyperlipidemia.

First authorship is shared by Li Li, Zhou Jiawei, and Wang Shuai. This study was supported by grants from the National Natural Science Foundation of China (81870106, 82070138, 82000139) and the Zhejiang Provincial Natural Science Foundation (LZ18H080001). Senior authors include professor Aiming Liu from Ningbo University School of Medicine. The authors would like to express gratitude to the Center of Cryo-Electron Microscopy and the Laboratory Animal Center of Zhejiang University School for their professional assistance.