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Article: Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling

TitleSmad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling
Authors
KeywordsAngiotensin II
Cardiac remodeling
Hypertension
Smad3
TGF-β
Issue Date2010
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/
Citation
Hypertension, 2010, v. 55 n. 5, p. 1165-1171 How to Cite?
Abstract
Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-β/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin II infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P<0.05), an increase in left ventricular mass (P<0.05), and the development of cardiac fibrosis and inflammation, including upregulation of transforming growth factor-β1, connective tissue growth factor, collagen I/III, α-smooth muscle actin, interleukin 1β, tumor necrosis factor-α, monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and an increase in macrophage and T-cell infiltration in left ventricular tissues (all P<0.01, respectively). Additional studies in vitro also revealed that angiotensin II-induced cardiac fibrosis and inflammation were prevented in Smad3 KO cardiac fibroblasts. Inactivation of both Smad3 and nuclear factor κB/p65 signaling pathways was a key mechanism by which Smad3 KO mice were protected from angiotensin II-mediated hypertensive cardiac remodeling. In conclusion, Smad3 plays an essential role in hypertensive cardiac remodeling. Results from this study suggest that targeting Smad3 may be a novel therapeutic strategy for hypertensive cardiovascular disease. Copyright © 2010 American Heart Association. All rights reserved.
Descriptionlink_to_OA_fulltext
Persistent Identifierhttp://hdl.handle.net/10722/135220
ISSN
2013 Impact Factor: 7.632
2013 SCImago Journal Rankings: 3.702
ISI Accession Number ID
References

 

Author Affiliations
  1. National Institute of Diabetes and Digestive and Kidney Diseases
  2. The University of Hong Kong
  3. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorHuang, XRen_HK
dc.contributor.authorChung, ACKen_HK
dc.contributor.authorYang, Fen_HK
dc.contributor.authorYue, Wen_HK
dc.contributor.authorDeng, Cen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorLan, HYen_HK
dc.date.accessioned2011-07-27T01:30:12Z-
dc.date.available2011-07-27T01:30:12Z-
dc.date.issued2010en_HK
dc.identifier.citationHypertension, 2010, v. 55 n. 5, p. 1165-1171en_HK
dc.identifier.issn0194-911Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/135220-
dc.descriptionlink_to_OA_fulltext-
dc.description.abstractAlthough Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-β/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin II infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P<0.05), an increase in left ventricular mass (P<0.05), and the development of cardiac fibrosis and inflammation, including upregulation of transforming growth factor-β1, connective tissue growth factor, collagen I/III, α-smooth muscle actin, interleukin 1β, tumor necrosis factor-α, monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and an increase in macrophage and T-cell infiltration in left ventricular tissues (all P<0.01, respectively). Additional studies in vitro also revealed that angiotensin II-induced cardiac fibrosis and inflammation were prevented in Smad3 KO cardiac fibroblasts. Inactivation of both Smad3 and nuclear factor κB/p65 signaling pathways was a key mechanism by which Smad3 KO mice were protected from angiotensin II-mediated hypertensive cardiac remodeling. In conclusion, Smad3 plays an essential role in hypertensive cardiac remodeling. Results from this study suggest that targeting Smad3 may be a novel therapeutic strategy for hypertensive cardiovascular disease. Copyright © 2010 American Heart Association. All rights reserved.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/en_HK
dc.relation.ispartofHypertensionen_HK
dc.subjectAngiotensin IIen_HK
dc.subjectCardiac remodelingen_HK
dc.subjectHypertensionen_HK
dc.subjectSmad3en_HK
dc.subjectTGF-βen_HK
dc.subject.meshAngiotensin II - pharmacology-
dc.subject.meshHypertension - chemically induced - physiopathology-
dc.subject.meshInflammation - prevention and control-
dc.subject.meshSmad3 Protein - deficiency - genetics - physiology-
dc.subject.meshVentricular Remodeling - drug effects - genetics - physiology-
dc.titleSmad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodelingen_HK
dc.typeArticleen_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/HYPERTENSIONAHA.109.147611en_HK
dc.identifier.pmid20231525en_HK
dc.identifier.scopuseid_2-s2.0-77951499390en_HK
dc.identifier.hkuros187298en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951499390&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume55en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1165en_HK
dc.identifier.epage1171en_HK
dc.identifier.isiWOS:000276672500019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHuang, XR=7410248090en_HK
dc.identifier.scopusauthoridChung, ACK=7103291604en_HK
dc.identifier.scopusauthoridYang, F=35182193900en_HK
dc.identifier.scopusauthoridYue, W=36106565300en_HK
dc.identifier.scopusauthoridDeng, C=7202302536en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridLan, HY=35783008500en_HK

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