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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Oxidized LDL-mediated macrophage survival involves elongation factor-2 kinase
Johnny H Chen1, Maziar Riazy, Ewan M Smith
1Department of Medicine, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Arteriosclerosis, Thrombosis, and Vascular Biology
|November 8, 2008
Summary
Oxidized LDL (oxLDL) promotes macrophage survival by increasing intracellular calcium and activating eEF2 kinase, a novel pathway that blocks apoptosis in early atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Atherosclerosis Pathogenesis
Background:
- Macrophage survival and proliferation are critical in early atherosclerotic lesion development.
- Oxidized low-density lipoprotein (oxLDL) is a key mediator in atherosclerosis, inhibiting macrophage apoptosis.
- The precise mechanism of oxLDL-mediated macrophage survival requires further investigation.
Purpose of the Study:
- To elucidate the signaling pathway by which oxLDL promotes macrophage survival.
- To investigate the role of intracellular calcium and eEF2 kinase in oxLDL-induced survival.
- To understand how oxLDL affects protein synthesis in macrophages.
Main Methods:
- Measurement of intracellular calcium ([Ca(2+)](i)) oscillations in response to oxLDL.
- Assessing the activation of eukaryotic elongation factor-2 kinase (eEF2 kinase) and p38 MAP kinase.
- Utilizing selective eEF2 kinase inhibitors to determine its role in oxLDL-mediated survival.
- Analyzing the effect of oxLDL on protein synthesis via eEF2 phosphorylation.
Main Results:
- OxLDL, unlike native LDL (nLDL), triggers immediate, oscillatory increases in intracellular calcium.
- Oxidized LDL activates calcium/calmodulin-dependent eEF2 kinase, an effect dependent on calcium mobilization.
- Inhibition of eEF2 kinase reverses oxLDL's prosurvival effect, leading to macrophage apoptosis.
- Oxidized LDL inhibits the activation of p38 MAP kinase, a negative regulator of eEF2 kinase.
- Oxidized LDL activates eEF2 kinase, leading to eEF2 phosphorylation, inhibition, and decreased protein synthesis.
Conclusions:
- Oxidized LDL blocks macrophage apoptosis through a novel signaling pathway involving calcium mobilization and eEF2 kinase activation.
- This pathway highlights a critical mechanism in the pathogenesis of early atherosclerotic lesions.
- Targeting this pathway could offer new therapeutic strategies for atherosclerosis.
