Inhibition of ABCA1 protein degradation promotes HDL cholesterol efflux capacity and RCT and reduces atherosclerosis in mice.

Journal of Lipid Research
LinZhang HuangHaiBo Zhu

Abstract

ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that the transcriptional upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts HDL function. Employing the small molecule triacetyl-3-hydroxyphenyladenosine (IMM-H007), we determined how the attenuation of ABCA1 protein degradation affects HDL cholesterol efflux capacity, RCT, and atherosclerotic lesion formation. Pulse-chase analysis revealed that IMM-H007 inhibits ABCA1 degradation and facilitates its cell-surface localization in macrophages, and additional studies in macrophages showed that IMM-H007 thereby promotes cholesterol efflux. IMM-H007 treatment of Paigen diet-fed mice caused an increase in circulating HDL level, it increased the cholesterol efflux capacity of HDL, and it enhanced in vivo RCT from macrophages to the plasma, liver, and feces. Furthermore, ABCA1 degradation suppression by IMM-H007 reduced atherosclerotic plaque formation in apoE(-/-) mice. Thus, via effects on both ABCA1-expressing cells and circulating HDL function, the inhibition of ABCA1 protein degradation by IMM-H007 prom...Continue Reading

References

Sep 4, 1990·The American Journal of Cardiology·P W Wilson
Aug 1, 1994·The Journal of Clinical Investigation·C PásztyE M Rubin
Apr 3, 2004·Nature Reviews. Drug Discovery·Neil Ruderman, Marc Prentki
Jul 28, 2007·The Journal of Clinical Investigation·Xun WangDaniel J Rader
Nov 10, 2007·The Journal of Clinical Investigation·Laurent Yvan-CharvetAlan R Tall
May 22, 2009·Journal of Lipid Research·Reijiro ArakawaShinji Yokoyama
Jun 3, 2009·Nature Reviews. Cardiology·Danielle Duffy, Daniel J Rader
Dec 25, 2009·Journal of Visualized Experiments : JoVE·Luke GabrielHaley Melikian
Jan 16, 2010·Circulation Research·Harumi Uto-KondoKatsunori Ikewaki
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tadahaya MizunoYuichi Sugiyama
May 31, 2011·Journal of Asian Natural Products Research·Yang SunHai-Bo Zhu
Aug 13, 2011·Biochimica Et Biophysica Acta·Shinji YokoyamaSumiko Abe-Dohmae
Nov 15, 2011·Biochimica Et Biophysica Acta·Natalie FournierJean-Louis Paul
Nov 17, 2011·The New England Journal of Medicine·William E BodenWilliam Weintraub
Feb 9, 2012·Current Protocols in Immunology·E Maganto-GarciaA H Lichtman
Apr 10, 2012·The Journal of Clinical Investigation·Yuan ZhangIra G Schulman
Sep 11, 2012·Nature Medicine·Daniel J Rader, Alan R Tall
Nov 7, 2012·The New England Journal of Medicine·Gregory G SchwartzUNKNOWN dal-OUTCOMES Investigators
Feb 2, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Elise F VillardMaryse Guerin
May 28, 2013·DNA and Cell Biology·Yun-cheng LvChao-ke Tang

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Citations

Jan 6, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wen-Xuan ZhangSong Wu
Jun 6, 2016·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Lian GuNong Tang
Jul 5, 2016·Acta Pharmacologica Sinica·Yu-Zhou GuiYi-Ping Wang
Jul 8, 2016·Current Opinion in Lipidology·Dmitri Sviridov, Yury I Miller
Nov 20, 2016·Biotechnology and Bioengineering·Dongming XieQuinn Zhu
Apr 6, 2018·Circulation Journal : Official Journal of the Japanese Circulation Society·Min ZhangChao-Ke Tang
Nov 6, 2017·Current Atherosclerosis Reports·Jacques Genest, Hong Y Choi
Apr 16, 2018·Science China. Life Sciences·Hanxiao OuZhongcheng Mo
Jun 15, 2019·Biomolecules·Jelena MilicJürgen Bernhagen
Jan 22, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Shi-Lin TangChao-Ke Tang
Jul 10, 2019·Biochemical and Biophysical Research Communications·Xiong WangLing Tao
Mar 7, 2021·Biology of Reproduction·Naomi C BernecicBart M Gadella
Sep 11, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Camryn L JohnsonW David Merryman
Oct 13, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ilaria ZanottiMarina Cuchel

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