Eicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1-dependent cholesterol efflux through cyclic AMP/protein kinase A signaling pathway in THP-1 macrophage-derived foam cells
Authors: Xin Ma
Jim Xiang
Chao-Ke Tang
Ji Xiao
Zhong-Cheng Mo
Xiao-Xu Li
Duan-Fang Liao
Yan-Wei Hu
Xie-Hong Liu
Journal: Atherosclerosis (2009)
Discipline: CLINICAL MEDICINE
Keywords: ABCA1; cholesterol efflux; unsaturated fatty acids; EPA; cAMP/PKA pathway
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, Hunan 421001 China.

Abstract:  ABCA1 is a key mediator of cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of RCT in vivo. Unsaturated fatty acids can inhibit cholesterol efflux from macrophages by increasing degradation of ABCA1. However, the detailed mechanisms of ABCA1 regulation by unsaturated fatty acids are not fully understood. In the present study, we investigated the effects of EPA on ABCA1 expression and ABCA1-dependent cholesterol efflux and examined the role of cAMP/PKA pathway on the regulation of ABCA1 by EPA in THP-1 macrophage-derived foam cells. Results showed that EPA significantly destabilized ABCA1 protein and reduced ABCA1-dependent cholesterol efflux but had no effect on ABCA1 mRNA expression. We also revealed that EPA markedly reduced cAMP level and PKA activity and ABCA1 serine phosphorylation. PKA-specific activation by PKA agonist markedly compensated the down-regulation of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux by EPA, while, siRNA of PKA leaded to reduce of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux more significantly than EPA. However, EPA-Induced enhancement of degradation rate of ABCA1 protein did not change by treatment with PKA agonist or PKA-siRNA. These results provide evidence that EPA may have dual negative effects on ABCA1 activity by decreasing ABCA1 protein level and by reducing PKA-mediated ABCA1 serine phosphorylation in THP-1 macrophage-derived foam cells. 

Retracted: No

PubPeer comments:
 Figure 3. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. Besides manipulations with Western blot images, across these papers, there is a pattern of bar graphs that look too similar but aren t 100% identical. Here is just an example. ![file] , 
 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.917 :  Editorial expression of concern: u201cEicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1-dependent cholesterol efflux through cyclic AMP protein kinase A signaling pathway in THP-1 macrophage-derived foam cellsu201d[Atherosclerosis Volume 204, Issue 2, June 2009, Pages e35-e43]. Published:June 25, 2021. The Editors of Atherosclerosis are issuing an expression of concern to alert readers that credible concerns have been raised regarding the quality of some data in the article above. See also https: retractionwatch.com 2021 07 09 they-seem-to-mean-business-cardiology-journal-flags-papers-cited-hundreds-of-times ,