Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
Toxicol Appl Pharmacol. 2011 Oct 15;256(2):146-53. doi: 10.1016/j.taap.2011.08.001. Epub 2011 Aug 7.
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.
饮用水中的砷是一个全球性的环境健康问题，暴露于砷可能会增加心血管和脑血管疾病的死亡率，这很可能是通过导致动脉粥样硬化实现的。然而，砷暴露后动脉粥样硬化形成的机制仍不清楚。为了研究砷暴露后动脉粥样硬化的形成机制，并探索高胆固醇饮食（HCD）在这一过程中的作用，我们用基础饮食或 HCD 喂养自发性高血压大鼠和 Wistar 京都大鼠，并在不同年龄和顺序下用含砷饮用水连续喂养 20 周。我们在预定的时间间隔测量高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇、甘油三酯、热休克蛋白 70（HSP 70）和高敏 C 反应蛋白（hs-CRP），并测定肝脏中胆固醇酯转移蛋白-1（CETP-1）和肝 X 受体β（LXRβ）的表达。通过对主动脉进行苏木精和伊红染色来确定动脉粥样硬化的程度。20 周后，我们发现砷单独或与 HCD 联合使用可能会促进动脉粥样硬化的形成，同时会短暂增加 HSP 70 和 hs-CRP。早期联合暴露会降低 HDL-C/LDL-C 比值，但在 30 周之前不会改变总胆固醇和甘油三酯的水平。CETP-1 和 LXRβ 的活性均受到抑制，早期联合暴露时抑制作用最为明显。总之，砷暴露可能通过改变胆固醇代谢中的逆向胆固醇转运，以及抑制 LXRβ和 CETP-1 的表达来诱导动脉粥样硬化。为了降低与砷相关的动脉粥样硬化相关死亡率，防止在生命早期从环境中接触砷是一个重要的因素。
