Elevated Neuropeptide Y in Endothelial Dysfunction Promotes Macrophage Infiltration and Smooth Muscle Foam Cell Formation

Frontiers in Immunology
Bongkun ChoiEun-Ju Chang

Abstract

Endothelial dysfunction has been linked to vascular inflammation and foam cell formation but the underlying mechanisms still remain unclear. We sought to define the factors inducing inflammation and smooth muscle foam cell formation under endothelial dysfunction using endothelial nitric oxide synthase (eNOS)-deficient mice. Vascular smooth muscle cells (VSMCs) from eNOS-deficient mice displayed increased expression of macrophage-related genes and elevated lipid uptake. Neuropeptide Y (NPY) was upregulated in the aorta from the eNOS-deficient mice and promoted macrophage chemotaxis toward VSMCs while enhancing the activity of matrix metalloproteinase-3. Notably, NPY induced lipid uptake in VSMCs, facilitating smooth muscle foam cell formation, in association with enhanced expression of genes related to modified low-density lipoprotein uptake and macrophages. NPY was augmented by inflammatory pentraxin 3 (PTX3) in VSMCs. PTX3 enhanced macrophage migratory capacity through the NPY/neuropeptide Y receptor axis and this effect was attenuated by pharmacological inhibition with a receptor-specific antagonist. These observations suggest that endothelial dysfunction leads to the elevation of NPY that amplifies vascular inflammation by i...Continue Reading

References

Nov 1, 1990·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·J ThybergB A Bottger
Mar 1, 1986·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·L JonassonG K Hansson
Aug 30, 1988·Biochemical and Biophysical Research Communications·A K MyersZ Zukowska-Grojec
Apr 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·R RossL Harker
May 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·K J Williams, I Tabas
Jan 1, 1993·Current Opinion in Nephrology and Hypertension·T PedrazziniB Waeber
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·E G SheselyO Smithies
Aug 1, 1998·Circulation Research·Z Zukowska-GrojecD S Grant
Jun 18, 1999·Hypertension·H M StaussP B Persson
Feb 26, 2000·Acta Physiologica Scandinavica·H M StaussP B Persson
Feb 7, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·S KawashimaM Yokoyama
May 15, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Michael S RolphGöran K Hansson
May 30, 2002·Biological Chemistry·Homero RubboCarlos Batthyány
Dec 20, 2002·Nature·Peter Libby
Mar 4, 2003·Journal of Lipid Research·Anissa Abderrahim-FerkouneEz-Zoubir Amri
Apr 25, 2003·Canadian Journal of Physiology and Pharmacology·Zofia ZukowskaLijun Li
Aug 9, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Hiroyuki HaoMarie-Luce Bochaton-Piallat
Jun 17, 2004·Circulation·Jean Davignon, Peter Ganz
Sep 1, 2004·Neuropeptides·Shu LinHerbert Herzog
Mar 18, 2005·Annual Review of Immunology·Cecilia GarlandaAlberto Mantovani
Sep 30, 2005·The American Journal of Pathology·Huijun SunJianglin Fan
Dec 7, 2005·The Journal of Experimental Medicine·Julie WhewayFabienne Mackay
Dec 13, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bing HanMingyao Liu
Jun 6, 2006·Cytokine & Growth Factor Reviews·Dimitris TousoulisChristodoulos Stefanadis
Sep 11, 2007·Journal of Clinical Immunology·Alberto MantovaniBarbara Bottazzi
Jan 29, 2008·The Journal of Pathology·As SavchenkoM Naito
Jan 3, 2009·PLoS Genetics·Svati H ShahElizabeth R Hauser
Dec 7, 2010·Trends in Cardiovascular Medicine·Sima Allahverdian, Gordon A Francis
Apr 7, 2011·Journal of Cardiovascular Translational Research·Lijun LiZofia Zukowska
Dec 7, 2011·Amino Acids·Mirjana Dimitrijević, Stanislava Stanojević

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Citations

Aug 9, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jia ShiFan He
Apr 3, 2020·Nature Reviews. Nephrology·Davide ViggianoGiovambattista Capasso
Jul 28, 2020·Journal of Cellular Physiology·Weiqiang WuShu Lin
Oct 31, 2020·Frontiers in Immunology·Wei-Can ChenShu Lin
Mar 13, 2021·Frontiers in Cardiovascular Medicine·Yan-Li ZhengHui-Li Lin
Jul 25, 2021·International Journal of Molecular Sciences·Masaki TanakaYoshihisa Watanabe

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Datasets Mentioned

BETA
GSE123855

Methods Mentioned

BETA
PCR
electrophoresis
fluorescence microscopy
Chip
ELISA

Software Mentioned

Zen

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