Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism

Abstract

Epidemiological studies have shown that arsenic exposure increases atherosclerosis, but the mechanisms underlying this relationship are unknown. Monocytes, macrophages and platelets play an important role in the initiation of atherosclerosis. Circulating monocytes and macrophages bind to the activated vascular endothelium and migrate into the sub-endothelium, where they become lipid-laden foam cells. This process can be facilitated by platelets, which favour monocyte recruitment to the lesion. Thus, we assessed the effects of low-to-moderate arsenic exposure on monocyte adhesion to endothelial cells, platelet activation and platelet-monocyte interactions. We observed that arsenic induces human monocyte adhesion to endothelial cells in vitro. These findings were confirmed ex vivo using a murine organ culture system at concentrations as low as 10 ppb. We found that both cell types need to be exposed to arsenic to maximize monocyte adhesion to the endothelium. This adhesion process is specific to monocyte/endothelium interactions. Hence, no effect of arsenic on platelet activation or platelet/leukocyte interaction was observed. We found that arsenic increases adhesion of mononuclear cells via increased CD29 binding to VCAM-1, an adhesion molecule found on activated endothelial cells. Similar results were observed in vivo, where arsenic-exposed mice exhibit increased VCAM-1 expression on endothelial cells and increased CD29 on circulating monocytes. Interestingly, expression of adhesion molecules and increased binding can be inhibited by antioxidants in vitro and in vivo. Together, these data suggest that arsenic might enhance atherosclerosis by increasing monocyte adhesion to endothelial cells, a process that is inhibited by antioxidants.

Evaluation of the possible Immunomodulatory and Neuroprotective effects of γ-irradiated basil (Ocimum basilicum) against arsenic toxicity in rats

“…In our study, it has been observed that the levels of HB, RBC, PLT, NEU, and LYM are decreased signi cantly with a marked increase in the HCT, WBC, MON and reticulocyte count in rats exposed to arsenic compared to the control group. The results are consistent with some studies (Kajiguchi et al, 2005; Bhattacharya and Haldar, 2012; Sumedha and Miltonprabu, 2013; Lemaire et al, 2015;Ghosh et al, 2017;Su et al, 2018). This effect of Arsenic exposure on the hematopoietic system may be attributed to the mechanisms of arsenic toxicity which may induce hemolysis and erythrophagocytosis through increased oxidation of sulfhydryl groups in hemoglobin and decreased oxygen intake by cells as a result of decreased intracellular glutathione, which decreases the lifespan of erythrocytes (Abdul et al, 2015).…”

Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort

“…24,25 Adhesion molecules allow mononuclear cells to attach to the endothelium, a key step in atherosclerotic initiation. In experimental studies, As elevates circulating vascular inflammatory marker levels, including ICAM1 and VCAM1 26–28 , increases monocyte adhesion to the vascular endothelium via increased binding to VCAM1 28 and increases atherosclerotic lesion formation, along with expression of inflammatory mediators, such as monocyte chemoattractant protein 1 (MCP1), at vascular lesion sites. 29 Levels of these circulating markers may predict future cardiovascular disease risk 30–33 and of these, soluble VCAM1 and ICAM1 have been consistently related to chronic As exposure in studies among adults in Bangladesh.…”

Arsenic and the immune system

“…Epidemiological studies carried out in various countries demonstrate that arsenic significantly increases the risk of atherosclerosis [55,56]. Several mechanisms may contribute to the development of atherosclerosis, including general pro-inflammatory cytokine secretion [10], increased ROS production [8], enhanced monocyte adhesion to vascular endothelium [57] and reduced cholesterol efflux from macrophages [7]. In murine models, at least, methylated metabolites and arsenic-3-methyltransferase play major roles in these proatherogenic effects of arsenic [58].…”