Cadmium is a highly toxic metal that is present in phosphate fertilizers, and the incidence of cadmium poisoning in the general population has increased, mainly due to cigarette smoking. Once absorbed, cadmium accumulates in the tissues, causing harmful effects including high blood pressure, endothelial damage and oxidative stress. Oxidative stress is known to efficiently produce oxidized low-density lipoprotein and consequently atherosclerosis, mainly in the aorta. However, the mechanisms through which endothelial damage is induced by cadmium have not been elucidated. Thus, the aim of this study was to investigate the effects of this metal in the isolated aorta and the possible role of oxidative stress. Rats received 100 mg.L−1 cadmium chloride (CdCl2) in the drinking water or distilled water alone for four weeks. The pressor effect of cadmium was followed throughout the exposure period by tail plethysmography. At the end of the fourth week, the blood cadmium content was established, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine and sodium nitroprusside was analyzed in the context of endothelium denudation and incubation with L-NAME, apocynin, losartan, enalapril, superoxide dismutase (SOD) or catalase. We observed an increased response to phenylephrine in cadmium-treated rats. This increase was abolished by catalase and SOD incubation. Apocynin treatment reduced the phenylephrine response in both treatment groups, but its effect was greater in cadmium-treated rats, and NOX2 expression was greater in the cadmium group. These results suggested that cadmium in blood concentrations similar to those found in occupationally exposed populations is able to stimulate NOX2 expression, contributing to oxidative stress and reducing NO bioavailability, despite enhanced eNOS expression. These findings suggest that cadmium exposure promotes endothelial damage that might contribute to inflammation, vascular injury and the development of atherosclerosis.

Objective B cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in abdominal aortic aneurysms (AAA), however, it is unknown whether B cell depletion therapy affects AAA growth. Using experimental models of murine AAA, we aim to examine the effect of B cell depletion on AAA formation. Approach and Results Wild-type or Apolipoprotein E knockout mice were treated with mouse monoclonal anti-CD20 or control antibodies and subjected to an elastase perfusion or angiotensin II-infusion model to induce AAA, respectively. Anti-CD20 antibody treatment significantly depleted B1 and B2 cells, and strikingly suppressed AAA growth in both models. B cell depletion resulted in lower circulating IgM levels, but did not affect the levels of IgG or cytokine/chemokine levels. Although the total number of leukocyte remained unchanged in elastase perfused aortas following anti-CD20 antibody treatment, the number of B cell subtypes was significantly lower. Interestingly, plasmacytoid dendritic cells (pDCs) expressing the immunomodulatory enzyme indole 2,3-dioxygenase (IDO) were detected in the aortas of B cell depleted mice. In accordance with an increase in IDO+ pDCs, the number of regulatory T cells was higher while the expression of pro-inflammatory genes was lower in aortas of B cell depleted mice. In a coculture model, presence of B cells significantly lowered the number of IDO+ pDCs without affecting total pDC number. Conclusions The present results demonstrate that B cell depletion protects mice from experimental AAA formation and promotes emergence of an immunosuppressive environment in aorta.

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