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Application of multianalyte microphysiometry to characterize macrophage metabolic responses to oxidized LDL and effects of an apoA-1 mimetic

Kimmel, Dannielle W and Dole, William and Cliffel, David E (2013) Application of multianalyte microphysiometry to characterize macrophage metabolic responses to oxidized LDL and effects of an apoA-1 mimetic. Biochemical and Biophysical Research Communications, 431 (2). pp. 181-185. ISSN 0006291X

Abstract

Although the interaction of macrophages with oxidized low density liopoprotein (oxLDL) is critical to the pathogenesis of atherosclerosis, relatively little is known about their metabolic response to oxLDL. Our development of the multianalyte microphysiometer (MAMP) allows for simultaneous measurement of extracellular metabolic substrates and products in real-time. Here, we use the MAMP to study changes in the metabolic rates of RAW-264.7 cells undergoing respiratory burst in response to oxLDL. These studies indicate that short duration exposure of macrophages to oxLDL results in time-dependent increases in glucose and oxygen consumption and in lactate production and extracellular acidification rate. Since apolipoprotein A-I (apoA-I) and apoA-I mimetics prevent experimental atherosclerosis, we hypothesized that the metabolic response of the macrophage during respiratory burst can be modulated by apoA-I mimetics. We tested this hypothesis by examining the effects of the apoA-I peptide mimetic, L-4F, alone and complexed with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) on the macrophage metabolic response to oxLDL. L-4F and the DMPC/L-4F complexes attenuated the macrophage respiratory burst in response to oxLDL. The MAMP provides a novel approach for studying macrophage ligand-receptor interactions and cellular metabolism and our results provide new insights into the metabolic effects of oxLDL and mechanism of action of apoA-I mimetics. © 2013 Elsevier Inc.

Item Type: Article
Additional Information: The apoA1 mimetic (L-4F) used in this in vitro study was obtained from Bruin Pharmaceuticals and Dr Alan Fogelman and is no longer an active Novartis collaborative project. The manuscript has been reviewed by Dr Fogelman and approved for publication submission.
Keywords: Apolipoprotein A-I mimetics Macrophage Microphysiometry Oxidative burst Oxidized LDL Respiratory burst
Date Deposited: 25 Oct 2017 00:45
Last Modified: 25 Jan 2019 00:46
URI: https://oak.novartis.com/id/eprint/7253

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