title: Conditional expression of the type 2 angiotensin II receptor in mesenchymal stem cells inhibits neointimal formation after arterial injury.
abstract: Percutaneous coronary interventions (PCIs) are an effective treatment for obstructive coronary artery diseases. However, the procedure's success is limited by remodeling and formation of neointima. In the present study, we engineered rat mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R) using a tetracycline-regulated system that can strictly regulate AT2R expression. We tested the ability of the modified MSCs to reduce neointima formation following arterial injury. We subjected rats to balloon injury, and reverse transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R expression in normal rat arteries. Low expression of AT2R was observed at 28 days after balloon-induced injury. Interestingly, MSCs alone were unable to reduce neointimal hyperplasia after balloon-induced injury; after transplantation of modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R expression and inhibited osteopontin mRNA expression, as well as neointimal formation. Taken together, these results suggest that transplantation of MSCs conditionally expressing AT2R could effectively suppress neointimal hyperplasia following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled gene induction system may be useful for the management of arterial injury after PCI.
authors.affiliation: Department of Cardiology, Southwest Hospital, Third Military Medical University and Chongqing Institute of Interventional Cardiology, Chongqing, 400038, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Miao
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: He
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Jing
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D002460:Cell Line; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006965:Hyperplasia; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; C506897:Spp1 protein, rat; D053495:Osteopontin; D004318:Doxycycline