Suppression of atherogenesis by delivery of TGFbeta1ACT using adeno-associated virus type 2 in LDLR knockout mice

Biochemical and Biophysical Research Communications
Dayuan LiJawahar L Mehta

Abstract

TGFbeta(1) deficiency has been attributed to the development of atherosclerosis. There is, however, little direct evidence for this concept. To examine this hypothesis, low-density lipoprotein receptor knockout (LDLR(-/-)) mice were injected via tail vein with recombinant adeno-associated virus type 2 (rAAV) carrying a bioactive TGFbeta(1) mutant (AAV/TGFbeta1ACT, n=10) or granulocyte-macrophage-colony stimulating factor (AAV/GM-CSF, n=10, a negative control) or saline (n=9, control), and then put on a high cholesterol diet. At 18 weeks, blood lipids were found to be similarly elevated in all LDLR(-/-) mice. TGFbeta1ACT and GM-CSF (DNA, mRNA, and protein) were highly expressed in the tissues of mice given TGFbeta1ACT or AAV/GM-CSF, respectively, showing sustained transfection following gene delivery by the systemic route. Saline-treated and AAV/GM-CSF-treated LDLR(-/-) mice showed extensive areas of atherosclerotic lesion formation. There was evidence of intense oxidative stress (nitrotyrosine staining), inflammation (CD68 staining), and expression of adhesion molecules and the ox-LDL receptor LOX-1 (gene array analysis) in the atherosclerotic tissues. Importantly, atherosclerotic lesion formation was markedly inhibited in the ...Continue Reading

References

May 25, 1990·Nucleic Acids Research·S W QianM B Sporn
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·P L Hermonat, N Muzyczka
Apr 1, 1996·The Journal of Nutrition·I Jialal, S Devaraj
Mar 21, 1998·Current Opinion in Lipidology·S Devaraj, I Jialal
Feb 12, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Y LiuP L Hermonat
Mar 10, 2000·Cytokine & Growth Factor Reviews·T A McCaffrey
May 3, 2002·Journal of the American College of Cardiology·Jawahar L Mehta, Dayuan Li
Jun 18, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Esther LutgensMat J A P Daemen
Feb 25, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ying Dong XuNasreen Khalil
Mar 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Dayuan LiJawahar L Mehta
Apr 8, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Hongjiang ChenJawahar L Mehta
May 14, 2003·The Journal of Cell Biology·Gediminas CepinskasPeter R Kvietys
Jul 25, 2003·Biochemical and Biophysical Research Communications·Bo HuJawahar L Mehta
Dec 31, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·David J Grainger
Aug 7, 2004·Stroke; a Journal of Cerebral Circulation·Francesco CipolloneEttore Porreca
Jan 25, 2005·Cardiovascular Research·Franck LebrinPeter Ten Dijke
Feb 3, 2005·Tissue Engineering·Nalini AgrawalPaul L Hermonat
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos

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Citations

Mar 28, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew D FrutkinDavid A Dichek
Sep 20, 2007·Journal of Cell Science·Chun-Lin ChenJung San Huang
Aug 3, 2014·Current Atherosclerosis Reports·Michael Lehrke, Corinna Lebherz
Mar 4, 2008·Biochimica Et Biophysica Acta·Kelly J Gordon, Gerard C Blobe
Nov 27, 2007·Biochemical and Biophysical Research Communications·Abhijit DandapatJawahar L Mehta
May 5, 2007·Circulation Research·Jawahar L MehtaTatsuya Sawamura
Apr 20, 2017·Circulation Research·Reiner K W MailerGöran K Hansson
Sep 16, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Anna-Karin L Robertson, Göran K Hansson
Nov 1, 2007·Journal of Cellular Physiology·Chun-Lin ChenJung San Huang
Jun 13, 2019·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·C Martín-GonzálezE González-Reimers
Mar 29, 2014·International Journal of Molecular Sciences·Stefan NeațuHermenegildo Garcia
May 2, 2014·European Journal of Dental Education : Official Journal of the Association for Dental Education in Europe·M S AhmadG L Borromeo
Nov 18, 2010·Journal of Speech, Language, and Hearing Research : JSLHR·Jennifer Horner, Fred D Minifie
Mar 3, 2007·Journal of Leukocyte Biology·Jana Barlic, Philip M Murphy
Jun 26, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Chang-Ping HuJawahar L Mehta
Nov 10, 2010·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Hong-Miao TaoBei Shao

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