Neovascularization and Angiogenic Gene Expression Following Chronic Arsenic Exposure in Mice

Overview

Journal Cardiovasc Toxicol

Specialties Cardiology & Vascular Diseases
Toxicology

Date 2005 Mar 2

PMID 15738583

Citations 29

Authors

Nicole V Soucy

Debra Mayka

Linda R Klei

Antonia A Nemec

John A Bauer

Aaron Barchowsky

Affiliations

Soon will be listed here.

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.

Citing Articles

Non-essential heavy metal effects in cardiovascular diseases: an overview of systematic reviews.

Nucera S, Serra M, Caminiti R, Ruga S, Passacatini L, Macri R Front Cardiovasc Med. 2024; 11:1332339.

PMID: 38322770 PMC: 10844381. DOI: 10.3389/fcvm.2024.1332339.

Contaminant Metals and Cardiovascular Health.

Lundin K, Qadeer Y, Wang Z, Virani S, Leischik R, Lavie C J Cardiovasc Dev Dis. 2023; 10(11).

PMID: 37998508 PMC: 10671885. DOI: 10.3390/jcdd10110450.

Metabolic Derangement by Arsenic: a Review of the Mechanisms.

Bibha K, Akhigbe T, Hamed M, Akhigbe R Biol Trace Elem Res. 2023; 202(5):1972-1982.

PMID: 37670201 DOI: 10.1007/s12011-023-03828-4.

Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights.

Huang J, El-Kersh K, Mann K, James K, Cai L Toxicol Appl Pharmacol. 2022; 454:116247.

PMID: 36122736 PMC: 9941893. DOI: 10.1016/j.taap.2022.116247.

A Clinical Perspective on Arsenic Exposure and Development of Atherosclerotic Cardiovascular Disease.

Kaur G, Desai K, Chang I, Newman J, Mathew R, Bangalore S Cardiovasc Drugs Ther. 2022; 37(6):1167-1174.

PMID: 35029799 DOI: 10.1007/s10557-021-07313-9.

References

Abernathy C, Liu Y, LONGFELLOW D, APOSHIAN H, Beck B, Fowler B . Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect. 1999; 107(7):593-7. PMC: 1566656. DOI: 10.1289/ehp.99107593. View

Engel R, Receveur O, Smith A . Vascular effects of chronic arsenic exposure: a review. Epidemiol Rev. 1994; 16(2):184-209. DOI: 10.1093/oxfordjournals.epirev.a036150. View

Calderon R . The epidemiology of chemical contaminants of drinking water. Food Chem Toxicol. 2000; 38(1 Suppl):S13-20. DOI: 10.1016/s0278-6915(99)00133-7. View

Wu H, Yang W, Wang M, Shi G . Impaired fibrinolysis in patients with Blackfoot disease. Thromb Res. 1993; 72(3):211-8. DOI: 10.1016/0049-3848(93)90188-t. View

Barchowsky A, Dudek E, Treadwell M, Wetterhahn K . Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med. 1996; 21(6):783-90. DOI: 10.1016/0891-5849(96)00174-8. View

Lee M, Jung B, Chung S, Bae O, Lee J, Park J . Arsenic-induced dysfunction in relaxation of blood vessels. Environ Health Perspect. 2003; 111(4):513-7. PMC: 1241437. DOI: 10.1289/ehp.5916. View

Barchowsky A, Roussel R, Klei L, James P, Ganju N, Smith K . Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways. Toxicol Appl Pharmacol. 1999; 159(1):65-75. DOI: 10.1006/taap.1999.8723. View

Tseng C, Chong C, Tseng C, Hsueh Y, Chiou H, Tseng C . Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic villages in Taiwan. Toxicol Lett. 2002; 137(1-2):15-21. DOI: 10.1016/s0378-4274(02)00377-6. View

Bagnato A, Spinella F . Emerging role of endothelin-1 in tumor angiogenesis. Trends Endocrinol Metab. 2002; 14(1):44-50. DOI: 10.1016/s1043-2760(02)00010-3. View

10.

Rahman M, Tondel M, Ahmad S, Chowdhury I, Faruquee M, Axelson O . Hypertension and arsenic exposure in Bangladesh. Hypertension. 1999; 33(1):74-8. DOI: 10.1161/01.hyp.33.1.74. View

11.

Simeonova P, Hulderman T, Harki D, Luster M . Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice. Environ Health Perspect. 2003; 111(14):1744-8. PMC: 1241717. DOI: 10.1289/ehp.6332. View

12.

Rossman T, Uddin A, Burns F, Bosland M . Arsenite cocarcinogenesis: an animal model derived from genetic toxicology studies. Environ Health Perspect. 2002; 110 Suppl 5:749-52. PMC: 1241238. DOI: 10.1289/ehp.02110s5749. View

13.

Liu Z, Shen J, Carbrey J, Mukhopadhyay R, Agre P, Rosen B . Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc Natl Acad Sci U S A. 2002; 99(9):6053-8. PMC: 122900. DOI: 10.1073/pnas.092131899. View

14.

Loomans C, Dao H, van Zonneveld A, Rabelink T . Is endothelial progenitor cell dysfunction involved in altered angiogenic processes in patients with hypertension?. Curr Hypertens Rep. 2004; 6(1):51-4. DOI: 10.1007/s11906-004-0011-y. View

15.

Koenig W . Haemostatic risk factors for cardiovascular diseases. Eur Heart J. 1998; 19 Suppl C:C39-43. View

16.

Scotland R, Vallance P, Ahluwalia A . Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. Br J Pharmacol. 1999; 128(6):1229-34. PMC: 1571762. DOI: 10.1038/sj.bjp.0702930. View

17.

Morishige K, Shimokawa H, Matsumoto Y, Eto Y, Uwatoku T, Abe K . Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo. Cardiovasc Res. 2003; 57(2):572-85. DOI: 10.1016/s0008-6363(02)00710-1. View

18.

Cho A, Reidy M . Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res. 2002; 91(9):845-51. DOI: 10.1161/01.res.0000040420.17366.2e. View

19.

Galis Z, Johnson C, Godin D, Magid R, Shipley J, Senior R . Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res. 2002; 91(9):852-9. DOI: 10.1161/01.res.0000041036.86977.14. View

20.

Carter D, Aposhian H, Gandolfi A . The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review. Toxicol Appl Pharmacol. 2003; 193(3):309-34. DOI: 10.1016/j.taap.2003.07.009. View