HMGB1 Promotes Ox-LDL-induced Endothelial Cell Damage by Inhibiting PI3K/Akt Signaling Pathway

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2022 Dec 21

PMID 36544080

Authors

Xin Huo

Boyou Su

Guoti Qin

Liming Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Atherosclerosis is the pathological basis of cardio-cerebrovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for atherosclerosis. Ox-LDL leads to endothelial cell (EC) damage and dysfunction through various processes and promotes the occurrence and deterioration of atherosclerosis. High mobility group box-1 (HMGB1) is a protein associated with cellular damage. In the present study, the effect of HMGB1 on ox-LDL-induced EC damage was determined and the underlying mechanism explored.

Materials And Methods: Human umbilical vein ECs (HUVECs) were exposed to ox-LDL to induce endothelial damage and changes in HMGB1 expression level were detected using western blotting analysis and reverse transcription-quantitative PCR. To observe the effect of HMGB1 on ox-LDL-induced damage, the HMGB1 expression was downregulated with siRNA, and cell viability, cytotoxicity, and apoptosis rate were assessed. HUVECs were pretreated with LY294002, an inhibitor of the PI3K/Akt pathway, to determine whether the effect of HMGB1 on damage is via the PI3K-Akt pathway.

Results: The results showed that ox-LDL can upregulate HMGB1 expression in HUVECs and downregulation of HMGB1 expression can prevent ox-LDL-induced damage in HUVECs. Furthermore, the effect of HMGB1 on ox-LDL-induced damage could be promoted by inhibiting the PI3K/Akt signaling pathway.

Conclusion: The results indicate HMGB1 may be a promising research target to alleviate ox-LDL-induced EC damage.

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