title: 3-morpholinosydnonimine participates in the attenuation of neointima formation via inhibition of annexin A2-mediated vascular smooth muscle cell migration.
abstract: 3-Morpholinosydnonimine (SIN-1) affects vascular smooth muscle cell migration and proliferation, processes essential for atherosclerosis. However, the mechanism by which SIN-1 exerts these effects has not been elucidated. We used 2-DE followed by MALDI-TOF/TOF MS to identify responses in protein expression to SIN-1 in rat aortic smooth muscle. Platelet-derived growth factor-BB increased cell migration and proliferation in rat aortic smooth muscle cells, and subsequent SIN-1 treatment inhibited it. Administration of SIN-1 in vivo attenuated neointima formation in balloon-injured rat carotid arteries. Proteomic analysis showed that glutathione peroxidase and 40S ribosomal protein S12 were differentially expressed in aortic strips exposed to SIN-1. Expression of annexin A2 was decreased by SIN-1. Platelet-derived growth factor-BB-induced cell migration was increased and inhibited in rat aortic smooth muscle cells with overexpression and knockdown of annexin A2 gene, respectively. The expression of annexin A2 was increased in vascular neointima compared with the intact control, which was inhibited by SIN-1 treatment. These results demonstrate that SIN-1 may attenuate vascular neointima formation by inhibiting annexin A2-mediated migration. Therefore, annexin A2 may be a potential target for therapeutic strategies for atherosclerosis.
authors.affiliation: Department of Physiology, School of Medicine, Konkuk University, Danwol-dong, Chungju, Korea.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Philyoung
authors.initials: P
authors.lastname: Lee
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Jung
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Jiang
authors.forename: Chang-Kwon
authors.initials: CK
authors.lastname: Lee
authors.forename: Hai Yue
authors.initials: HY
authors.lastname: Lin
authors.forename: Hyun
authors.initials: H
authors.lastname: Kang
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D058426:Neointima / Q000188:drug therapy*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D017306:Annexin A2; D020030:Nitric Oxide Donors; D010982:Platelet-Derived Growth Factor; D020543:Proteome; D020574:Proto-Oncogene Proteins c-sis; D014665:Vasodilator Agents; D000077214:Becaplermin; C002385:linsidomine; D008981:Molsidomine