Suppression of Vascular Macrophage Activation by Nitro-Oleic Acid and its Implication for Abdominal Aortic Aneurysm Therapy.

Cardiovascular Drugs and Therapy
Yang ZhaoY Eugene Chen

Abstract

Abdominal aortic aneurysm (AAA) is one of the leading causes of death in the developed world and is currently undertreated due to the complicated nature of the disease. Herein, we aimed to address the therapeutic potential of a novel class of pleiotropic mediators, specifically a new drug candidate, nitro-oleic acid (NO2-OA), on AAA, in a well-characterized murine AAA model. We generated AAA using a mouse model combining AAV.PCSK9-D377Y induced hypercholesterolemia with angiotensin II given by chronic infusion. Vehicle control (PEG-400), oleic acid (OA), or NO2-OA were subcutaneously delivered to mice using an osmotic minipump. We characterized the effects of NO2-OA on pathophysiological responses and dissected the underlying molecular mechanisms through various in vitro and ex vivo strategies. Subcutaneous administration of NO2-OA significantly decreased the AAA incidence (8/28 mice) and supra-renal aorta diameters compared to mice infused with either PEG-400 (13/19, p = 0.0117) or OA (16/23, p = 0.0078). In parallel, the infusion of NO2-OA in the AAA model drastically decreased extracellular matrix degradation, inflammatory cytokine levels, and leucocyte/macrophage infiltration in the vasculature. Administration of NO2-OA red...Continue Reading

References

May 1, 1997·Journal of Vascular Surgery·D R HolmesJ M Reilly
Apr 16, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Francis J MillerNeal L Weintraub
Feb 20, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Tanja K RudolphBruce A Freeman
Jun 19, 2010·Circulation Research·Jifeng ZhangY Eugene Chen
Nov 23, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Eva H C TangPeter Libby
Mar 2, 2011·The Journal of Biological Chemistry·Emilia KansanenAnna-Liisa Levonen
May 5, 2011·Journal of Computational Chemistry·Aurélien GrosdidierOlivier Michielin
Jun 1, 2011·Nucleic Acids Research·Aurélien GrosdidierOlivier Michielin
Sep 21, 2011·Chemical Reviews·Francisco J SchopferBruce A Freeman
May 10, 2012·PloS One·Utako YokoyamaYoshihiro Ishikawa
May 19, 2012·The American Journal of Pathology·Richard Y CaoColin D Funk
Oct 5, 2012·The British Journal of Surgery·S G ThompsonUNKNOWN Multicentre Aneurysm Screening Study (MASS) Group
Nov 13, 2012·The Journal of Biological Chemistry·Gustavo BonacciFrancisco J Schopfer
Dec 4, 2012·Free Radical Biology & Medicine·Steven R WoodcockFrancisco J Schopfer
Apr 27, 2013·Journal of Lipid Research·Sonia R SalvatoreFrancisco J Schopfer
Aug 16, 2013·American Journal of Physiology. Renal Physiology·Ying LiuTianxin Yang
Oct 18, 2013·Journal of Lipid Research·Mercedes CamachoLuis Vila
May 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Rebecca L CharlesPhilip Eaton
Sep 20, 2015·Free Radical Biology & Medicine·Meghan Delmastro-GreenwoodStacy Gelhaus Wendell
Dec 29, 2015·Frontiers in Bioscience (Landmark Edition)·Luis VillacortaY Eugene Chen
Jan 9, 2017·Free Radical Biology & Medicine·Hana VerescakovaMichaela Pekarova
Apr 14, 2017·Nature Reviews. Cardiology·Juliette RaffortZiad Mallat
Feb 2, 2018·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Jun 27, 2018·Nitric Oxide : Biology and Chemistry·Francisco J SchopferBruce A Freeman
Dec 5, 2018·Nature Chemical Biology·Yosuke ToyodaTakuya Kobayashi
Feb 15, 2019·Circulation Research·Nicholas J SwerdlowMarc L Schermerhorn
Feb 15, 2019·Circulation Research·Raymundo Alain Quintana, W Robert Taylor
Feb 15, 2019·Circulation Research·Jan H Lindeman, Jon S Matsumura
Feb 16, 2019·Redox Biology·Nicholas K H KhooBruce A Freeman
Jun 15, 2019·Trends in Endocrinology and Metabolism : TEM·Francisco J Schopfer, Nicholas K H Khoo
Aug 14, 2019·International Journal of Molecular Sciences·Łukasz GutowskiDorota Formanowicz
Aug 28, 2019·Methods in Molecular Biology·Gabriela Bitencourt-Ferreira, Walter Filgueira de Azevedo
Oct 11, 2019·Current Opinion in Physiology·Nicholas K H Khoo, Francisco J Schopfer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Aortic Aneurysm

An aortic aneurysm is the weakening and bulging of the blood vessel wall in the aorta. This causes dilatation of the aorta, which is usually asymptomatic but carries the risk of rupture and hemorrhage. Find the latest research on aortic aneurysms here.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.