CD44 Deficiency in Mice Protects the Heart Against Angiotensin Ii-Induced Cardiac Fibrosis

Shock
Li-Wang YangZhi-Qing Zhao

Abstract

This study tested the hypothesis that CD44 is involved in the development of cardiac fibrosis via angiotensin II (Ang II) AT1 receptor-stimulated TNFα/NFκB/IκB signaling pathways. Study was conducted in C57BL/6 wild type and CD44 knockout mice subjected to Ang II infusion (1,000 ng/kg/min) using osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1 receptor blocker, telmisartan at a dose of 10 mg/kg/d. Results indicated that Ang II enhances expression of the AT1 receptor, TNFα, NFκB, and CD44 as well as downregulates IκB. Further analyses revealed that Ang II increases macrophage migration, augments myofibroblast proliferation, and induces vascular/interstitial fibrosis. Relative to the Ang II group, treatment with telmisartan significantly reduced expression of the AT1 receptor and TNFα. These changes occurred in coincidence with decreased NFκB, increased IκB, and downregulated CD44 in the intracardiac vessels and intermyocardium. Furthermore, macrophage migration and myofibroblast proliferation were inhibited and fibrosis was attenuated. Knockout of CD44 did not affect Ang II-stimulated AT1 receptor and modulated TNFα/NFκB/IκB signaling, but significantly reduced macrophage/myofibroblast-mediated fi...Continue Reading

References

Jan 30, 2004·The Journal of Laboratory and Clinical Medicine·Yao SunKarl T Weber
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adil I KhanPaul Kubes
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter HuebenerNikolaos G Frangogiannis
Jul 4, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Maureen M TedescoRonald L Dalman
Apr 13, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Gyeong In Mun, Yong Chool Boo
Jul 16, 2010·Cardiovascular Therapeutics·Paul J LijnenRobert H Fagard
Nov 10, 2010·Journal of Molecular and Cellular Cardiology·Marcin DobaczewskiNikolaos G Frangogiannis
Mar 10, 2012·Circulation Research·Qinghang LiuJeffery D Molkentin
Jun 5, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jingping SunRobert J McKallip
Nov 13, 2015·Journal of Molecular and Cellular Cardiology·Chao ChenAna Maria Manso
Nov 26, 2015·Journal of Molecular and Cellular Cardiology·Justin Hartupee, Douglas L Mann
Jan 13, 2016·Comprehensive Physiology·Matthew A BoegeholdJulian H Lombard
Jan 23, 2016·Nature Communications·Bárbara González-TeránGuadalupe Sabio
Apr 28, 2016·Seminars in Cell & Developmental Biology·Jonathan LeorTal Konfino
Dec 14, 2016·Annual Review of Physiology·Kevin M Vannella, Thomas A Wynn
Feb 6, 2017·European Journal of Heart Failure·Mariann GyöngyösiFaiez Zannad
Apr 22, 2017·Frontiers in Pharmacology·Lu FangAnthony M Dart
Apr 30, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Go KuwaharaAlan Dardik
May 12, 2017·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Ning-Ping WangZhi-Qing Zhao
Jun 2, 2017·Experimental and Therapeutic Medicine·Jing TianLing Niu
Jun 3, 2017·JACC. Heart Failure·Levent Cerit
Jul 2, 2017·Advances in Experimental Medicine and Biology·Alexei Ilinykh, Alexander R Pinto

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Citations

Nov 27, 2018·Shock·Hongkuan Fan, Andrew J Goodwin
Nov 3, 2020·Cardiovascular Research·Nikolaos G Frangogiannis

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