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Hypoxia enhances lipid uptake in macrophages: Role of the scavenger receptors Lox1, SRA, and CD36


Crucet, M; Wuest, Sophia J A; Spielmann, P; Luescher, T F; Wenger, R H; Matter, C M (2013). Hypoxia enhances lipid uptake in macrophages: Role of the scavenger receptors Lox1, SRA, and CD36. Atherosclerosis, 229(1):110-117.

Abstract

The core of advanced atherosclerotic plaques turns hypoxic as the arterial wall thickens and oxygen diffusion capacity becomes impaired. Macrophage-derived foam cells play a pivotal role in atherosclerotic plaque formation by expressing scavenger receptors that regulate lipid uptake. However,the role of hypoxia in scavenger receptor regulation remains incompletely understood. Methods and results: Using RT-qPCR, flow cytometry and immunoblotting, we found that mRNA and protein expression levels of the scavenger receptor A (SRA) and the cluster of differentiation 36 (CD36)were upregulated by oxidized low-density lipoprotein (oxLDL), but decreased following exposure of macrophages to hypoxia. In contrast, lectin-like oxLDL receptor (Lox-1) mRNA and protein levels were upregulated under hypoxic conditions. Flow cytometry confirmed the increased lipid content in macrophages after exposure to 0.2% oxygen and the hypoxia-mimetic dimethyloxalylglycine (DMOG). Antibody-mediated blocking of Lox-1 receptor decreased the hypoxic induction of oxLDL uptake and lipid content. RNAi-mediated knock-down of hypoxia-inducible factor (HIF)-1a in macrophages attenuated the hypoxic induction of Lox-1. Conclusions: Hypoxia increases lipid uptake into macrophages and differentially regulates the expression of oxLDL receptors. Lox-1 plays a major role in hypoxia-induced foam cell formation which is, at least in part, mediated by HIF-1alpha.

Abstract

The core of advanced atherosclerotic plaques turns hypoxic as the arterial wall thickens and oxygen diffusion capacity becomes impaired. Macrophage-derived foam cells play a pivotal role in atherosclerotic plaque formation by expressing scavenger receptors that regulate lipid uptake. However,the role of hypoxia in scavenger receptor regulation remains incompletely understood. Methods and results: Using RT-qPCR, flow cytometry and immunoblotting, we found that mRNA and protein expression levels of the scavenger receptor A (SRA) and the cluster of differentiation 36 (CD36)were upregulated by oxidized low-density lipoprotein (oxLDL), but decreased following exposure of macrophages to hypoxia. In contrast, lectin-like oxLDL receptor (Lox-1) mRNA and protein levels were upregulated under hypoxic conditions. Flow cytometry confirmed the increased lipid content in macrophages after exposure to 0.2% oxygen and the hypoxia-mimetic dimethyloxalylglycine (DMOG). Antibody-mediated blocking of Lox-1 receptor decreased the hypoxic induction of oxLDL uptake and lipid content. RNAi-mediated knock-down of hypoxia-inducible factor (HIF)-1a in macrophages attenuated the hypoxic induction of Lox-1. Conclusions: Hypoxia increases lipid uptake into macrophages and differentially regulates the expression of oxLDL receptors. Lox-1 plays a major role in hypoxia-induced foam cell formation which is, at least in part, mediated by HIF-1alpha.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:25 Sep 2013 14:30
Last Modified:07 Dec 2017 22:37
Publisher:Elsevier
ISSN:0021-9150
Funders:Integrative Human Physiology, Swiss National Science Foundation (31003A_146203), Consejo Nacional de Ciencia y Tecnologia Mexico
Publisher DOI:https://doi.org/10.1016/j.atherosclerosis.2013.04.034

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