Related Experiment Video
Updated: Aug 22, 2026
Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
Published on: January 7, 2019
Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
Ellen Knutsen Rydberg1, Alexandra Krettek, Christina Ullström
1Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, SE 413 45 Göteborg, Sweden. ellen.rydberg@wlab.gu.se
Objective:
Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques.
Methods And Results:
To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries.
Conclusions:
In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
Insights
Hypoxia significantly increases macrophage-mediated oxidation of low-density lipoprotein (LDL) by upregulating 15-lipoxygenase-2 (15-LOX-2). This enzyme is found in hypoxic macrophages and atherosclerotic plaques, suggesting its role in atherogenesis.
Area of Science:
- Cardiovascular Biology
- Cellular Metabolism
- Atherosclerosis Research
Background:
- Macrophage oxidation of LDL is crucial in atherogenesis.
- Macrophages are present in hypoxic regions of atherosclerotic plaques.
Purpose of the Study:
- To investigate the role of hypoxia in macrophage-mediated LDL oxidation.
- To determine the expression and activity of 15-lipoxygenase-2 (15-LOX-2) under hypoxic conditions.
Main Methods:
- Human monocyte-derived macrophages were incubated with LDL under normoxic and hypoxic conditions.
- mRNA, protein expression, and enzyme activity of 15-LOX-2 were analyzed.
Main Results:
- Hypoxic macrophages exhibited significantly higher LDL oxidation compared to normoxic cells.
- 15-LOX-2 mRNA, protein expression, and enzyme activity were elevated in hypoxic macrophages.
- 15-LOX-2 was detected in macrophage-rich areas of carotid plaques.
Conclusions:
- Hypoxia induces 15-LOX-2 expression and activity in macrophages.
- 15-LOX-2 is present in atherosclerotic plaques.
- 15-LOX-2 may contribute to macrophage-mediated LDL oxidation in hypoxic atherosclerotic environments.
More Related Videos
07:46Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Related Concept Videos
01:38Inflammation
01:24Peroxisomes
01:24Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
01:26Coronary Artery Disease II: Pathophysiology
01:30Atherosclerosis I: Introduction