Peli1 induction impairs cardiac microvascular endothelium through Hsp90 dissociation from IRE1α.
Biochim Biophys Acta Mol Basis Dis
; 1865(10): 2606-2617, 2019 10 01.
Article
en En
| MEDLINE
| ID: mdl-31260751
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Proteínas Serina-Treonina Quinasas
/
Proteínas HSP90 de Choque Térmico
/
Ubiquitina-Proteína Ligasas
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Endorribonucleasas
/
Endotelio
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
China