title: Aortic smooth muscle cell alterations in mice systemically exposed to arsenic.
abstract: Previous epidemiological studies showed that chronic arsenic exposure is related to increased cardiovascular disease incidence. The detailed biochemical mechanisms by which arsenic exerts its effects remain unknown. Vascular disease progression is characterized by smooth muscle cell (SMC) phenotypic switching, vessel wall reorganization, and platelet-derived growth factor (PDGF) production. The objective of this study was to examine early biochemical and structural changes in the aortas of ICR mice systemically exposed to arsenic. Animals were fed sodium arsenite (20 mg/kg) via gavage 5 days/week or Milli-Q water only (control) for 8 weeks. Aortic proteins were subjected to two-dimensional (2-D) differential gel electrophoresis and proteomic studies. Two 2-D gel protein spots were identified as the same protein, smooth muscle (SM)22α, using proteomics. SM22α and Rho kinase 2 gene and protein expression were significantly decreased in the aortic tissue of arsenic-exposed mice compared with that of control mice. No atherosclerotic lesion formation or tissue injury was detected in the aortic wall of either the arsenic-fed or the control group. However, the percent (%) SMC area of the aortic wall was significantly decreased in arsenic-fed mice compared with that in control mice. Additionally, the expression levels of PDGF-BB and early growth response-1 (Egr-1) were significantly higher in the arsenic group than that in the control group. These findings reveal biochemical alterations of SM22α, PDGF, and Egr-1 in conjunction with decreased SMC area in the aortic wall of arsenic-fed mice. Arsenic may initiate aortic SMC alterations that subsequently lead to vascular dysfunction.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan. jaychen@kmu.edu.tw.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shin-Yin
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, College of Medicine, Kaohsiung Medical University and Hospital, Tzu-you 1st Road, Kaohsiung, Taiwan.
authors.forename: Rei-Cheng
authors.initials: RC
authors.lastname: Yang
authors.affiliation: Department of Dermatology, College of Medicine, Kaohsiung Medical University and Hospital, Tzu-you 1st Road, Kaohsiung, Taiwan.
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D000077214:Becaplermin; D002853:Chromatography, Liquid; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D008297:Male; D008813:Mice, Inbred ICR; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D040901:Proteomics / Q000379:methods; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D018053:Arsenites; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D020574:Proto-Oncogene Proteins c-sis; D017670:Sodium Compounds; C544013:alpha-smooth muscle actin, mouse; D000077214:Becaplermin; C017947:sodium arsenite; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases
keywords: Aorta; Aortic smooth muscle cell; Arsenic; Egr-1; Platelet-derived growth factor; Proteomics; SM22α; Sodium arsenite