Perrone Pasquale, Ortega-Luna Raquel, Manna Caterina, Álvarez-Ribelles Ángeles, Collado-Diaz Victor
Department of Precision Medicine, School of Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain.
Antioxidants (Basel). 2024 Dec 20;13(12):1576. doi: 10.3390/antiox13121576.
Mercury (Hg) is a highly toxic environmental contaminant that can harm human health, ultimately leading to endothelial dysfunction. Hg toxicity is partially mediated by the exposure of the cell membrane's surface of erythrocytes (RBCs) to phosphatidylserine (PS). In the context of these challenges, hydroxytyrosol, a phenolic compound of olive oil, has the ability to mitigate the toxic effects of Hg. This study aims to analyze the effect of Hg on the adhesion of RBCs and polymorphonuclear cells (PMNs) to the vascular endothelium and the potential protective effect of hydroxytyrosol, as these interactions are crucial in the development of cardiovascular diseases (CVDs). RBCs, PMNs, and human vein endothelial cells (HUVECs) were treated with increasing concentrations of HgCl and, in some cases, with hydroxytyrosol, and their adhesion to HUVECs and the expression of adhesion molecules were subsequently analyzed. Our results demonstrate that HgCl significantly increases the adhesion of both RBCs (2.72 ± 0.48 S.E.M., -value < 0.02) and PMNs (11.19 ± 1.96 S.E.M., -value < 0.05) to HUVECs and that their adhesiveness is significantly reduced following treatment with hydroxytyrosol (RBCs, 1.2 ± 1.18 S.E.M., -value < 0.02 and PMNs, 4.04 ± 1.35 S.E.M., -value < 0.06). Interestingly, HgCl does not alter the expression of adhesion molecules on either HUVECs or RBCs, suggesting that reduced exposure to PS is a key factor in hydroxytyrosol protection against HgCl-induced RBC adhesion to the endothelium. On the other hand, HgCl induces increased expression of several PMN adhesion molecules (CD11b 215.4 ± 30.83 S.E.M. -value < 0.01), while hydroxytyrosol inhibits their expression (e.g., CD11b 149 ± 14.35 S.E.M., -value < 0.03), which would seem to be the mechanism by which hydroxytyrosol restricts PMN-endothelium interactions. These results provide new insights into the molecular mechanisms through which hydroxytyrosol mitigates the harmful effects of Hg on cardiovascular health, highlighting its potential as a therapeutic agent that can reduce the cardiovascular risk related to heavy metal exposure.
汞（Hg）是一种剧毒的环境污染物，会损害人体健康，最终导致内皮功能障碍。汞的毒性部分是由红细胞（RBCs）细胞膜表面暴露于磷脂酰丝氨酸（PS）介导的。在这些挑战的背景下，橄榄油中的酚类化合物羟基酪醇有能力减轻汞的毒性作用。本研究旨在分析汞对红细胞和多形核细胞（PMNs）与血管内皮细胞黏附的影响以及羟基酪醇的潜在保护作用，因为这些相互作用在心血管疾病（CVDs）的发展中至关重要。用浓度递增的HgCl处理红细胞、多形核细胞和人静脉内皮细胞（HUVECs），在某些情况下还同时用羟基酪醇处理，随后分析它们与HUVECs的黏附情况以及黏附分子的表达。我们的结果表明，HgCl显著增加了红细胞（2.72±0.48标准误，P值<0.02）和多形核细胞（11.19±1.96标准误，P值<0.05）与HUVECs的黏附，而用羟基酪醇处理后它们的黏附性显著降低（红细胞，1.2±1.18标准误，P值<0.02；多形核细胞，4.04±1.35标准误，P值<0.06）。有趣的是，HgCl并未改变HUVECs或红细胞上黏附分子的表达，这表明减少PS的暴露是羟基酪醇保护细胞免受HgCl诱导的红细胞与内皮细胞黏附的关键因素。另一方面，HgCl诱导几种多形核细胞黏附分子的表达增加（CD11b 215.4±30.83标准误，P值<0.01），而羟基酪醇抑制它们的表达（例如，CD11b 149±14.35标准误，P值<0.03），这似乎是羟基酪醇限制多形核细胞与内皮细胞相互作用的机制。这些结果为羟基酪醇减轻汞对心血管健康有害影响的分子机制提供了新的见解，突出了其作为一种治疗剂的潜力，该治疗剂可降低与重金属暴露相关的心血管风险。
