title: GHSR deficiency suppresses neointimal formation in injured mouse arteries.
abstract: Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR-/-) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR-/-mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling.
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yahan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China; The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China. Electronic address: npwang@hsc.pku.edu.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000235:genetics / Q000503:physiopathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054440:Receptors, Ghrelin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Growth hormone secretagogue receptor; Muscle cell; Neointimal formation; Smooth