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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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/135220
ISSN
2015 Impact Factor: 6.294
2015 SCImago Journal Rankings: 3.702
ISI Accession Number ID
References

 

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.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.pmid20231525-
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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