Treatment of atherosclerosis by transplantation of bone endothelial progenitor cells over-expressed paraoxonase-1 gene by recombinant adeno-associated virus in rat.
Endothelial dysfunction/loss is a key event in the development of vascular diseases, including native atherosclerosis (AS). Recent studies have shown that endothelial progenitor cells (EPCs) have the ability to repair endothelial cells that have been lost or damaged following AS. As a result, the therapy of transplanting EPCs is a promising option for the treatment of AS. However, the therapeutic effect on AS with only EPCs transplantation has not been satisfactory. The upregulation of those genes, which prevent the progress of AS in EPCs, is a novel therapeutic strategy for AS. Because it can reduce macrophage foam cell formation and protect endothelial cells from the oxidation of low-density lipoprotein (ox-LDL), paraoxonase-1 (PON1) gene is a candidate for gene therapy in AS. In this study, a recombinant adeno-associated virus (rAAV) vector carrying the human paraoxonase-1 (hPON1) gene (rAAV-PON1) was constructed, and endothelial progenitor cells (EPCs) transfected with rAAV-PON1 were transplanted into the atherosclerosis model of Sprague-Dawley rats (SD rats). The results of doppler ultrasound and histological analysis showed that the group transplanted with the hPON1 gene-transfected EPCs was superior to the group transplanted only with the EPCs and was also better than the group with hPON1 gene injection alone. The results indicated that rAAV-mediated hPON1 gene-transfected EPCs is a potentially valuable new tool in the treatment of atherosclerosis.
Experimental Hematology Laboratory, Department of Physiology, Xiang-Ya School of Medicine, Central South University, Changsha 410008, China.
Feng
F
Wang
Jinfeng
J
Xue
Danjun
D
Wang
Xianyou
X
Wang
Shukun
S
Lu
Mengqun
M
Tan
D000818:Animals; D001011:Aorta / Q000473:pathology; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D007963:Leukocytes, Mononuclear; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism; D014162:Transfection / Q000379:methods
D043303:Aryldialkylphosphatase