title: Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice.
abstract: Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease.
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH, USA.
authors.forename: Nicole V
authors.initials: NV
authors.lastname: Soucy
authors.forename: Debra
authors.initials: D
authors.lastname: Mayka
authors.forename: Linda R
authors.initials: LR
authors.lastname: Klei
authors.forename: Antonia A
authors.initials: AA
authors.lastname: Nemec
authors.forename: John A
authors.initials: JA
authors.lastname: Bauer
authors.forename: Aaron
authors.initials: A
authors.lastname: Barchowsky
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000633:toxicity*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
chemical_list: D042501:Angiogenic Proteins; D001151:Arsenic
references.citation: Environ Health Perspect. 1999 Jul;107(7):593-7
references.pmid: 10379007
references.citation: Epidemiol Rev. 1994;16(2):184-209
references.pmid: 7713176
references.citation: Food Chem Toxicol. 2000;38(1 Suppl):S13-20
references.pmid: 10717366
references.citation: Thromb Res. 1993 Nov 1;72(3):211-8
references.pmid: 8303660
references.citation: Free Radic Biol Med. 1996;21(6):783-90
references.pmid: 8902524
references.citation: Environ Health Perspect. 2003 Apr;111(4):513-7
references.pmid: 12676608
references.citation: Toxicol Appl Pharmacol. 1999 Aug 15;159(1):65-75
references.pmid: 10448126
references.citation: Toxicol Lett. 2003 Jan 31;137(1-2):15-21
references.pmid: 12505429
references.citation: Trends Endocrinol Metab. 2003 Jan;14(1):44-50
references.pmid: 12475611
references.citation: Hypertension. 1999 Jan;33(1):74-8
references.pmid: 9931084
references.citation: Environ Health Perspect. 2003 Nov;111(14):1744-8
references.pmid: 14594625
references.citation: Environ Health Perspect. 2002 Oct;110 Suppl 5:749-52
references.pmid: 12426125
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6053-8
references.pmid: 11972053
references.citation: Curr Hypertens Rep. 2004 Feb;6(1):51-4
references.pmid: 14972094
references.citation: Eur Heart J. 1998 Apr;19 Suppl C:C39-43
references.pmid: 9597424
references.citation: Br J Pharmacol. 1999 Nov;128(6):1229-34
references.pmid: 10578136
references.citation: Cardiovasc Res. 2003 Feb;57(2):572-85
references.pmid: 12566130
references.citation: Circ Res. 2002 Nov 1;91(9):845-51
references.pmid: 12411400
references.citation: Circ Res. 2002 Nov 1;91(9):852-9
references.pmid: 12411401
references.citation: Toxicol Appl Pharmacol. 2003 Dec 15;193(3):309-34
references.pmid: 14678742
references.citation: Circulation. 2004 Jan 6;109(1):26-9
references.pmid: 14691044
references.citation: Environ Health Perspect. 1999 May;107(5):359-65
references.pmid: 10210691
references.citation: Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):504-10
references.pmid: 8624771
references.citation: Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3294-301
references.pmid: 9409325
references.citation: Science. 2003 May 9;300(5621):939-44
references.pmid: 12738852
references.citation: Thromb Res. 2002 Jan 1;105(1):55-62
references.pmid: 11864708
references.citation: J Natl Cancer Inst. 2002 Dec 18;94(24):1888-91
references.pmid: 12488483
references.citation: Free Radic Biol Med. 1999 Dec;27(11-12):1405-12
references.pmid: 10641735
references.citation: Blood. 2001 Mar 1;97(5):1514-6
references.pmid: 11222403
references.citation: Toxicol Appl Pharmacol. 2003 Nov 15;193(1):1-8
references.pmid: 14613711
references.citation: Chem Res Toxicol. 2004 Apr;17(4):555-63
references.pmid: 15089098
references.citation: Nature. 2000 Sep 14;407(6801):249-57
references.pmid: 11001068
references.citation: Semin Thromb Hemost. 2004 Feb;30(1):109-17
references.pmid: 15034802
references.citation: Chem Res Toxicol. 2003 Apr;16(4):460-8
references.pmid: 12703962
references.citation: Environ Health Perspect. 2003 Feb;111(2):155-59
references.pmid: 12573898
references.citation: FASEB J. 2003 Jan;17(1):67-9
references.pmid: 12475910
references.citation: Bull World Health Organ. 2002;80(2):173
references.pmid: 11953799
references.citation: Cardiovasc Diabetol. 2004 Feb 04;3:1
references.pmid: 14761253
references.citation: Circulation. 2002 Apr 16;105(15):1804-9
references.pmid: 11956123
references.citation: Circulation. 1999 Jan 5-12;99(1):111-20
references.pmid: 9884387
references.citation: Arch Toxicol Suppl. 1985;8:452-5
references.pmid: 3868376
references.citation: Br J Ind Med. 1983 Aug;40(3):280-4
references.pmid: 6871116
references.citation: Toxicol Sci. 2003 Dec;76(2):271-9
references.pmid: 12970581
references.citation: Cardiovasc Toxicol. 2002;2(1):63-73
references.pmid: 12189281
references.citation: Virchows Arch. 1997 Apr;430(4):321-5
references.pmid: 9134043
references.citation: Blood. 2000 Aug 15;96(4):1525-30
references.pmid: 10942401
references.citation: J Dermatol. 2002 Mar;29(3):123-30
references.pmid: 11990246