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Genetic deletion of LXR? prevents arsenic-enhanced atherosclerosis, but not arsenic-altered plaque composition.

ABSTRACT: Arsenic exposure has been linked to an increased incidence of atherosclerosis. Previously, we have shown in vitro and in vivo that arsenic inhibits transcriptional activation of the liver X receptors (LXRs), key regulators of lipid homeostasis. Therefore, we evaluated the role of LXR? in arsenic-induced atherosclerosis using the apoE(-/-) mouse model. Indeed, deletion of LXR? protected apoE(-/-) mice against the proatherogenic effects of arsenic. We have previously shown that arsenic changes the plaque composition in apoE(-/-) mice. Arsenic decreased collagen content in the apoE(-/-) model, and we have observed the same diminution in LXR?(-/-)apoE(-/-) mice. However, the collagen-producing smooth muscle cells (SMCs) were decreased in apoE(-/-), but increased in LXR?(-/-)apoE(-/-). Although transcriptional activation of collagen remained the same in SMC from both genotypes, arsenic-exposed LXR?(-/-)apoE(-/-) plaques had increased matrix metalloproteinase activity compared with both control LXR?(-/-)apoE(-/-) and apoE(-/-), which could be responsible for both the decrease in plaque collagen and the SMC invasion. In addition, arsenic increased plaque lipid accumulation in both genotypes. However, macrophages, the cells known to retain lipid within the plaque, were unchanged in arsenic-exposed apoE(-/-) mice, but decreased in LXR?(-/-)apoE(-/-). We confirmed in vitro that these cells retained more lipid following arsenic exposure and are more sensitive to apoptosis than apoE(-/-). Mice lacking LXR? are resistant to arsenic-enhanced atherosclerosis, but arsenic-exposed LXR?(-/-)apoE(-/-) mice still present a different plaque composition pattern than the arsenic-exposed apoE(-/-) mice.

SUBMITTER: Lemaire M

PROVIDER: S-EPMC4250850 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Genetic deletion of LXRα prevents arsenic-enhanced atherosclerosis, but not arsenic-altered plaque composition.

Lemaire Maryse M Lemarié Catherine A CA Flores Molina Manuel M Guilbert Cynthia C Lehoux Stéphanie S Mann Koren K KK

Toxicological sciences : an official journal of the Society of Toxicology 20140930 2

Arsenic exposure has been linked to an increased incidence of atherosclerosis. Previously, we have shown in vitro and in vivo that arsenic inhibits transcriptional activation of the liver X receptors (LXRs), key regulators of lipid homeostasis. Therefore, we evaluated the role of LXRα in arsenic-induced atherosclerosis using the apoE(-/-) mouse model. Indeed, deletion of LXRα protected apoE(-/-) mice against the proatherogenic effects of arsenic. We have previously shown that arsenic changes the ...[more]

PMID: 25273567

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Dataset Information

Genetic deletion of LXR? prevents arsenic-enhanced atherosclerosis, but not arsenic-altered plaque composition.

Publications

Genetic deletion of LXRα prevents arsenic-enhanced atherosclerosis, but not arsenic-altered plaque composition.

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