New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice

Circulation
W NiAkira Takeshita

Abstract

Monocyte recruitment into the arterial wall and its activation may be the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be a unique site-specific gene therapy. We devised a new strategy for anti-MCP-1 gene therapy to treat atherosclerosis by transfecting an N-terminal deletion mutant of the human MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E-knockout mice. This strategy effectively blocked MCP-1 activity and inhibited the formation of atherosclerotic lesions but had no effect on serum lipid concentrations. Furthermore, this strategy increased the lesional extracellular matrix content. We conclude that this anti-MCP-1 gene therapy may serve not only to reduce atherogenesis but also to stabilize vulnerable atheromatous plaques. This strategy may be a useful and feasible form of gene therapy against atherosclerosis in humans.

References

Jun 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S Ylä-HerttualaD Steinberg
Dec 1, 1987·Atherosclerosis·B PaigenR A Williams
Jun 1, 1997·The Journal of Clinical Investigation·S GuptaC Schindler
Jan 16, 1998·International Archives of Allergy and Immunology·S YamashiroT Yoshimura
Jan 14, 1999·The New England Journal of Medicine·R Ross
Feb 4, 1999·Nature Medicine·T UekiJ Fujimoto

❮ Previous
Next ❯

Citations

May 10, 2002·Clinical Cardiology·Uichi IkedaKazuyuki Shimada
Dec 12, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Wuzhou Wan, Philip M Murphy
Mar 30, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Yong Woo LeePaul H Kim
Jan 13, 2005·Basic Research in Cardiology·Alma Zernecke, Christian Weber
May 21, 2008·Current Atherosclerosis Reports·Ahmed Soliman, Patrick Kee
Feb 21, 2009·Current Atherosclerosis Reports·Carlos Gonzalez-Quesada, Nikolaos G Frangogiannis
Sep 28, 2012·Journal of Cardiovascular Translational Research·Melissa L Martin, Burns C Blaxall
Mar 7, 1983·FEBS Letters·M J Kime, P B Moore
Sep 12, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hironobu MitaniMasaaki Kimura
Aug 17, 2010·Acta Pharmacologica Sinica·Stavros ApostolakisDemetrios A Spandidos
Nov 3, 2005·Nature Clinical Practice. Cardiovascular Medicine·Robin P ChoudhuryDavid R Greaves
Nov 2, 2002·Nature Medicine·Andrew C Li, Christopher K Glass
Apr 29, 2009·Nature Reviews. Cardiology·Viviane Z Rocha, Peter Libby
Jun 24, 2009·The Journal of Experimental Medicine·Yosuke KayamaIssei Komuro
May 16, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Satish L DeshmaneBassel E Sawaya
Mar 17, 2004·Current Opinion in Lipidology·Christina A BursillDavid R Greaves
Aug 24, 2007·Clinical and Experimental Pharmacology & Physiology·G H Tesch
Feb 16, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Amanda C DoranColeen A McNamara
Feb 28, 2009·American Journal of Respiratory and Critical Care Medicine·Anderson J FerreiraMohan K Raizada
Sep 4, 2010·American Journal of Respiratory Cell and Molecular Biology·Michael J CutticaManfred Boehm
Jun 21, 2002·Circulation Journal : Official Journal of the Japanese Circulation Society·Kensuke Egashira
Jul 1, 2004·Circulation Journal : Official Journal of the Japanese Circulation Society·Kengo Fukushima KusanoTohru Ohe
Sep 29, 2012·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Jacek JawienRyszard Korbut
Jun 15, 2011·Bioscience, Biotechnology, and Biochemistry·Katsumi Imaizumi
Nov 19, 2003·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yasuharu TabaraTetsuro Miki
May 19, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Mitsuhisa KogaTsutomu Imaizumi
Oct 31, 2008·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Jun-ichiro KogaKenji Sunagawa
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Melissa HunterClay Marsh
Oct 15, 2011·Journal of Atherosclerosis and Thrombosis·Seigo MasudaKensuke Egashira
Aug 29, 2009·Journal of Atherosclerosis and Thrombosis·Tadashi YamakawaYasuo Terauchi
Sep 21, 2013·Cellular and Molecular Life Sciences : CMLS·Yao Yao, Stella E Tsirka
Jan 1, 2014·Future Neurology·Joseph S HudsonDavid M Hasan
Jul 27, 2014·The Journal of Endocrinology·Ronald J van der SluisMenno Hoekstra
Jan 21, 2014·Cardiology in Review·Georgios ChristodoulidisConstantine E Kosmas
Jul 16, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Xinyi JiangFan Yang
Nov 19, 2005·Expert Review of Cardiovascular Therapy·Pål AukrustJan Kristian Damås
Mar 20, 2004·Expert Review of Cardiovascular Therapy·Shiro Kitamoto, Kensuke Egashira
Jul 2, 2003·Expert Opinion on Investigational Drugs·W I de Boer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.