Protective Effects of Mesenchymal Stem Cells with Transient Overexpression of Hmgb1 on Balloon-Induced Carotid Artery Injury

Abstract

The first two authors contributed equally to this study Mesenchymal stem cells (MSC) playa crucial role in endothelial repair after artery injury. The high mobility group box 1 (HMGBl) is a key modulator of the homing of MSC to impaired artery and endothelialization. This study was aimed to determine whether balloon-induced carotid artery injury could be improved by transplantation with MSC modified by HMGBI. MSC were infected by adenoviral serotype 5 encoding recombinant green fluorescent protein (GFP) gene and HMGBI (ad5GFP-HMGBl). The expression ofHMGBl, vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected in MSC using Real-time PCR, Western blot and semi-quantitative immunohistochemical assays. In vivo, reendothelialization was examined in rats subjected to carotid artery injury. The homing of MSC was observed under fluorescence microscopy, and the levels of serum tumor necrosis factor-a (TNF-a) and C-reactive protein (CRP) was assessed by ELISA assay. As a result, compared with the MSC group, the expression of HMGBl, VEGF and PCNA was markedly increased, vascular reendothelialization was accelerated, and the levels of serum TNF-a and CRP were decreased in group ad5GFP and ad5GFP-HMGBl. Transplantation of MSC infected with adGFP-HMGBl strengthened the MSC effect. Taken together, modification ofHMGBl can enhance the protective effects ofMSC on balloon-induced carotid artery injury through up-regulation ofVEGF and PCNA expression and inhibition ofthe inflammatory response. HMGBI in MSC may represent a novel therapeutic target for the treatment of endothelial repair.