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

Abstract

Mesenchymal stem cells (MSC) play a crucial role in endothelial repair after artery injury. The high mobility group box 1 (HMGB1) 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 HMGB1. MSC were infected by adenoviral serotype 5 encoding recombinant green fluorescent protein (GFP) gene and HMGB1 (ad5GFP-HMGB1). The expression of HMGB1, 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-α (TNF-α) and C-reactive protein (CRP) was assessed by ELISA assay. As a result, compared with the MSC group, the expression of HMGB1, VEGF and PCNA was markedly increased, vascular reendothelialization was accelerated, and the levels of serum TNF-α and CRP were decreased in group ad5GFP and ad5GFP-HMGB1. Transplantation of MSC infected with adGFP-HMGB1 strengthened the MSC effect. Taken together, modification of HMGB1 can enhance the protective effects of MSC on balloon-induced carotid artery injury through up-regulation of VEGF and PCNA expression and inhibition of the inflammatory response. HMGB1 in MSC may represent a novel therapeutic target for the treatment of endothelial repair.