title: Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism.
abstract: Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.
authors.affiliation: Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
authors.forename: Tain-Junn
authors.initials: TJ
authors.lastname: Cheng
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Chuu
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chang
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Tsai
authors.forename: Kuan-Jung
authors.initials: KJ
authors.lastname: Chen
authors.forename: How-Ran
authors.initials: HR
authors.lastname: Guo
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000009:adverse effects*; D050197:Atherosclerosis / Q000139:chemically induced*; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000737:chemistry; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014280:Triglycerides / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014881:Water Supply
chemical_list: D001152:Arsenicals; D053480:Cholesterol Ester Transfer Proteins; D018840:HSP70 Heat-Shock Proteins; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D014280:Triglycerides; D014874:Water Pollutants, Chemical; D002097:C-Reactive Protein; D002784:Cholesterol