title: Activation of liver X receptor enhances the proliferation and migration of endothelial progenitor cells and promotes vascular repair through PI3K/Akt/eNOS signaling pathway activation.
abstract: Vascular endothelial injury is a major cause of many cardiovascular diseases. The proliferation and migration of endothelial progenitor cells (EPCs) play a pivotal role in endothelial regeneration and repair after vascular injury. Recently, liver X receptor (LXR) activation has been suggested as a potential target for novel therapeutic interventions in the treatment of cardiovascular disease. However, the effects of LXR activation on endothelial regeneration and repair, as well as EPC function, have not been investigated. In the present study, we demonstrate that LXRs, including LXRα and LXRβ, are expressed and functional in rat bone marrow-derived EPCs. Treatment with an LXR agonist, TO901317 (TO) or GW3965 (GW), significantly increased the proliferation and migration of EPCs, as well as Akt and eNOS phosphorylation in EPCs. Moreover, LXR agonist treatment enhanced the expression and secretion of vascular endothelial growth factor in EPCs. LXR agonists accelerated re-endothelialization in injured mouse carotid arteries in vivo. These data confirm that LXR activation may improve EPC function and endothelial regeneration and repair after vascular injury by activating the PI3K/Akt/eNOS pathway. We conclude that LXRs may be attractive targets for drug development in the treatment of cardiovascular diseases associated with vascular injury.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhexue
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: simpls@tmmu.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D001565:Benzoates; D001596:Benzylamines; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D052250:Nitric Oxide Synthase Type III; D057093:Orphan Nuclear Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides; C473027:GW 3965; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: EPCs; Endothelial regeneration and repair; LXR; Migration; Proliferation