Title
Peli1 Induction Impairs Cardiac Microvascular Endothelium Through Hsp90 Dissociation From IRE1α
Document Type
Article
Publication Date
10-1-2019
Description
Ameliorating cardiac microvascular injury is the most effective means to mitigate diabetes-induced cardiovascular complications. Inositol-requiring 1α (IRE1α), a sensor of endoplasmic reticulum stress, is activated by Toll like receptors (TLRs), and then promotes cardiac microvascular injury. Peli1 is a master regulator of TLRs and activates IRE1α. This study aims to investigate whether Peli1 in endothelial cells promotes diabetes-induced cardiac microvascular injury through activating IRE1α. Here we found that Peli1 was markedly up-regulated in cardiac endothelial cells of both diabetic mice and in AGEs-treated cardiac microvascular endothelial cells (CMECs). Peli1 deficiency in endothelial cells significantly alleviated diabetes-induced cardiac microvascular permeability, promoted microvascular regeneration, and suppressed apoptosis, accompanied by the attenuation of adverse cardiac remodeling. Furthermore, Peli1 deletion in CMECs ameliorated AGEs-induced damages in vitro. We identified heat shock protein 90 (Hsp90) as a potential binding partner for Peli1, and the Ring domain of Peli1 directly bound with Hsp90 to enhance IRE1α phosphorylation. Our study suggests that blocking Peli1 in endothelial cells may protect against diabetes-induced cardiac microvascular injury by restraining ER stress.
Citation Information
Zhao, Qianwen; Yang, Jie; Chen, Hao; Li, Jiantao; Que, L.; Zhu, Guoqing; Liu, Li; Ha, Tuanzhu; Chen, Qi; Li, Chuanfu; Xu, Yong; and Li, Yuehua. 2019. Peli1 Induction Impairs Cardiac Microvascular Endothelium Through Hsp90 Dissociation From IRE1α. Biochimica et Biophysica Acta - Molecular Basis of Disease. Vol.1865(10). 2606-2617. https://doi.org/10.1016/j.bbadis.2019.06.017 PMID: 31260751 ISSN: 0925-4439