Department of Biology, University of North Carolina at Greensboro, Greensboro, NC, 27402, USA.
Sci Rep. 2020 Jun 2;10(1):9023. doi: 10.1038/s41598-020-66444-5.
Cardiovascular disease (CVD) is the major cause of morbidity, mortality, and health care costs in the United States, and possibly around the world. Among the various risk factors of CVD, environmental and dietary exposures to mercury (Hg), a highly toxic metal traditionally regarded as a neurotoxin, has been recently suggested as a potential contributor towards human atherosclerotic development. In this study, we investigated the toxicity, type of cell death, dose-dependent uptake, and efflux of inorganic HgII (as HgCl) and methylmercury or MeHg (as CHHgCl) in EA.hy926 endothelial cells, as these two forms of Hg are often reported to be present in human blood among the general populations (~20-30% as HgII and ~70-80% as MeHg). Our results showed that HgII is more toxic than MeHg to the endothelial cells, owing to the higher uptake into the cytoplasm and perhaps importantly lower efflux of HgII by the cells, thus the "net" accumulation by the endothelial cells is higher for HgII than MeHg when exposed to the same Hg levels in the media. Furthermore, both HgII and MeHg were found to induce apoptotic and necrotic cell death. This study has important implications for the contributions of these two common Hg species to the development of atherosclerosis, an important process leading to CVD.
心血管疾病 (CVD) 是美国乃至全球发病率、死亡率和医疗保健费用的主要原因。在 CVD 的各种风险因素中，环境和饮食暴露于汞 (Hg)，一种传统上被认为是神经毒素的高度有毒金属，最近被认为是人类动脉粥样硬化发展的潜在因素。在这项研究中，我们研究了无机 HgII（如 HgCl）和甲基汞或 MeHg（如 CHHgCl）在 EA.hy926 内皮细胞中的毒性、细胞死亡类型、剂量依赖性摄取和外排，因为这两种形式的 Hg 经常在一般人群的血液中报告（20-30%为 HgII，70-80%为 MeHg）。我们的结果表明，HgII 比 MeHg 对内皮细胞更具毒性，这是由于 HgII 更容易进入细胞质，而且细胞对 HgII 的外排可能更低，因此当暴露于相同的 Hg 水平时，内皮细胞对 HgII 的“净”积累高于 MeHg。此外，研究还发现 HgII 和 MeHg 都能诱导细胞凋亡和坏死。这项研究对于这两种常见 Hg 物种对动脉粥样硬化发展的贡献具有重要意义，动脉粥样硬化是导致 CVD 的一个重要过程。
