CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells

Abstract

The present study demonstrates that CXCR4 gene transfer contributes to the enhanced in vivo reendothelialization capacity of EPCs. Up-regulation of CXCR4 in human EPCs may become a novel therapeutic target for endothelial repair.

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

“…However, the association of above-proposed signaling pathway based on our in vitro cell culture experiments is supported by the closed relationship between CXCR4 ⁄ JAK-2 signal and in vivo reendothelialization capacity of EPCs in elderly men. This is further evidenced by our recent study in which the transplantation of human EPCs overexpressing CXCR4 by gene transfer clearly accelerated reendothelialization in a nude mouse model of carotid artery injury, supporting the notion put forward here obtained by the exercise-mediated upregulation of CXCR4 ⁄ JAK-2 signal and augmentation of EPC reendothelialization capacity (Chen et al, 2010). Furthermore, flow-mediated vasodilation in the brachial artery is also significantly high in elderly men after exercise, suggesting an improvement of endothelial function probably partially related to the upregulation of EPC function and number with subsequently an enhanced EPC integration into defects of the endothelial cell layer and rejuvenescence of aging endothelial cells consistent to previous studies (Hill et al, 2003;Werner et al, 2003).…”

“…The CXCR4 has been shown to be involved in the homing of EPCs (Hristov et al, 2007a;Sainz & Sata, 2007;Chen et al, 2010). Our data showed the surface CXCR4 protein expression did not have difference between young and elderly men (p = NS) (Fig.…”

“…Endothelial progenitor cells were isolated and cultured as previously described (Asahara et al, 1997;Chen et al, 2010;Giannotti et al, 2010). After 7 days of culture, EPCs were defined as cells dually positive for 1,1¢-dioctadecyl-3,3,3¢,3¢-tetramethylindo-carbocyanine (DiI)-acetylated low-density lipoprotein (acLDL) uptake (Invitrogen, Carlsbad, CA, USA) and BS-1 lectin binding (Sigma-Aldrich, St. Louis, MO, USA) and endothelial markers were examined by flow cytometry analysis using CD31 (BD Pharmingen, San Digeo, CA, USA), von Willebrand factor (vWF) and kinase-insert domain receptor (KDR) (R&D Systems Inc, Minneapolis, MN, USA) as previously described (Chen et al, 2010).…”

“…After 7 days of culture, EPCs were defined as cells dually positive for 1,1¢-dioctadecyl-3,3,3¢,3¢-tetramethylindo-carbocyanine (DiI)-acetylated low-density lipoprotein (acLDL) uptake (Invitrogen, Carlsbad, CA, USA) and BS-1 lectin binding (Sigma-Aldrich, St. Louis, MO, USA) and endothelial markers were examined by flow cytometry analysis using CD31 (BD Pharmingen, San Digeo, CA, USA), von Willebrand factor (vWF) and kinase-insert domain receptor (KDR) (R&D Systems Inc, Minneapolis, MN, USA) as previously described (Chen et al, 2010). Based on the isolation and cultivation protocol, the adherent mononuclear cells were identified as early EPCs (Chen et al, 2010;Giannotti et al, 2010). Circulating EPCs were evaluated by the number of CD34+ ⁄ KDR+ and KDR+ ⁄ CD133 cells per 100 thousands PBMNCs by flow cytometry analysis (Beckman-Coulter, Fullerton, CA, USA) as previously described (Fadini et al, 2008).…”

“…There is increasing evidence that CXCR4 is a key regulator of homing and retention of EPCs at the sites of injured artery, suggesting that an enhanced CXCR4 expression may facilitate the endothelial repair capacity of EPCs (Hristov et al, 2007a;Sainz & Sata, 2007;Chen et al, 2010). However, the influences of physical exercise on endothelialization capacity and CXCR4 signaling of human EPCs are not clear in persons with aging.…”