Endothelial Progenitor Cells Reendothelialization Research Articles

Bimodal Imaging-Visible Nanomedicine Integrating CXCR4 and VEGFa Genes Directs Synergistic Reendothelialization of Endothelial Progenitor Cells.

A major challenge to treat vascular endothelial injury is the restoration of endothelium integrity in which endothelial progenitor cells (EPCs) plays a central role. Transplantation of EPCs as a promising therapeutic means is subject to two interrelated processes, homing and differentiation of EPCs in vivo, and thus a lack of either one may greatly affect the outcome of EPC‐based therapy. Herein, a polymeric nanocarrier is applied for the codelivery of CXCR4 and VEGFa genes to simultaneously promote the migration and differentiation of EPCs. Moreover, MRI T2 contrast agent SPION and NIR dye Cy7.5 are also loaded into the nanocarrier in order to track EPCs in vivo. Based on the synergistic effect of the two codelivered genes, an improved reendothelialization of EPCs is achieved in a rat carotid denuded model. The results show the potential of this bimodal imaging‐visible nanomedicine to improve the performance of EPCs in repairing arterial injury, which may push forward the stem cell‐based therapy of cardiovascular disease.

PGC-1α gene transfer restores adhesion and reendothelialization of endothelial progenitor cells from patients with hypertension.

Endothelial progenitor cells (EPCs) play an important role in endothelial vascular development and endothelial repair. The upregulation of functional gene expression in EPCs may contribute to the maintenance of EPC-based endothelial repair. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a powerful regulator of mitochondrial biogenesis and antioxidant defense, but its impact on early EPCs remains poorly understood. This study was designed to investigate whether decline in PGC-1α expression impairs in vitro adhesion, migration, and in vivo reendothelialization capacity of early EPCs from patients with hypertension. We engineered an over-expression of PGC-1α within EPCs from hypertensive patients, which were transduced with an adenoviral vector encoding the human PGC-1α gene. Then we tested the migration and adhesion function of EPCs in vitro and endothelium-reparative capacity in vivo with a nude mouse model of carotid artery injury. Our data revealed for the first time that PGC-1α expression of EPCs is lower in hypertensive patients than that in healthy subjects. Meanwhile, the in vitro adhesion and migration function, in vivo endothelial repair capacity of early EPCs were significantly reduced in hypertensive patients compared with normal subjects. Furthermore, PGC-1α gene transfer contributes to increased adhesion in vitro and enhanced endothelium-reparative capacity in vivo of EPCs from hypertensive patients through the augmented expression of PGC-1α. Thus, upregulation of PGC-1α expression of EPCs may be a novel complementary therapeutic target to increase endothelium-reparative capacity in hypertensive patients.

Glycogen synthase kinase 3β inhibition enhanced proliferation, migration and functional re-endothelialization of endothelial progenitor cells in hypercholesterolemia microenvironment.

Hypercholesterolemia impairs the quantity and function of endothelial progenitor cell. We hypothesized that glycogen synthase kinase 3β activity is involved in regulating biological function of endothelial progenitor cells in hypercholesterolemia microenvironment. For study, endothelial progenitor cells derived from apolipoprotein E-deficient mice fed with high-fat diet were used. Glycogen synthase kinase 3β activity was interfered with glycogen synthase kinase 3β inhibitor lithium chloride or transduced with replication defective adenovirus vector expressing catalytically inactive glycogen synthase kinase 3β (GSK3β-KM). Functions of endothelial progenitor cells, proliferation, migration, secretion and network formation of endothelial progenitor cells were assessed invitro. The expression of phospho-glycogen synthase kinase 3β, β-catenin and cyclinD1 in endothelial progenitor cells was detected by Western blot. The invivo function re-endothelialization and vasodilation were also analyzed by artery injury model transplanted with glycogen synthase kinase 3β-inhibited endothelial progenitor cells. We demonstrated that while the proliferation, migration, network formation as well as VEGF and NO secretion were impaired in apolipoprotein E-deficient endothelial progenitor cells, glycogen synthase kinase 3β inhibition significantly improved all these functions. Apolipoprotein E-deficient endothelial progenitor cells showed decreased phospho-glycogen synthase kinase 3β, β-catenin and cyclinD1 expression, whereas these signals were enhanced by glycogen synthase kinase 3β inhibition and accompanied with β-catenin nuclear translocation. Our invivo model showed that glycogen synthase kinase 3β inhibition remarkably increased re-endothelial and vasodilation. Taken together, our data suggest that inhibition of glycogen synthase kinase 3β is associated with endothelial progenitor cell biological functions both invitro and invivo. It might be an important interference target in hypercholesterolemia microenvironment.