File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Smad7 inhibits angiotensin II-induced hypertensive cardiac remodelling

TitleSmad7 inhibits angiotensin II-induced hypertensive cardiac remodelling
Authors
KeywordsSmad7
Ang II
Fibrosis
Inflammation
miR-29
Issue Date2013
Citation
Cardiovascular Research, 2013, v. 99, n. 4, p. 665-673 How to Cite?
AbstractAimsSmad7 plays a negative regulatory role in many inflammatory diseases, but its effect on hypertensive disease remains unknown. The present study tested the hypothesis that overexpression of Smad7 may have therapeutic potential for angiotensin II (Ang II)-mediated hypertensive cardiac remodelling.Methods and resultsHypertensive heart disease was induced in mice by subcutaneous infusion of Ang II for 28 days and treated with Smad7 by a non-invasive ultrasound-microbubble-mediated inducible Smad7 gene transfer. We found that cardiac Smad7 was largely reduced in the hypertensive heart and overexpression of cardiac Smad7 protected against the fall in the left ventricular (LV) ejection fraction (EF), an increase in LV mass, and cardiac inflammation and fibrosis such as up-regulation of pro-inflammatory cytokines (IL-1β, TNF-α) and fibrotic markers (collagen I, α-SMA), and infiltration of CD3+ T cells and F4/80+ macrophages. Further studies revealed that inactivation of the Sp1-TGF-β/Smad3-NF-κB (NF-κB, nuclear factor κB) pathways and prevention of cardiac miR-29 loss were mechanisms by which overexpression of Smad7 inhibited Ang II-mediated cardiac remodelling. Importantly, we also found that treatment with Smad7 when hypertensive cardiopathy established at day 14 halted the progression of cardiac injury by blunting the fall of EF and an increase in LV mass, and blocking TGF-β/Smad3-mediated cardiac fibrosis and NF-κB-driven inflammation.ConclusionSmad7 plays a protective role in Ang II-induced cardiac remodelling via mechanisms involving the Sp1-TGF-β/Smad-NF-κB-miR-29 regulatory network. Thus, Smad7 may be a novel therapeutic agent for hypertensive cardiovascular diseases. © 2013 The Author.
Persistent Identifierhttp://hdl.handle.net/10722/199928
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWei, Lihua-
dc.contributor.authorHuang, Xiaoru-
dc.contributor.authorZhang, Yang-
dc.contributor.authorLi, Youqi-
dc.contributor.authorChen, Hai-Yong-
dc.contributor.authorYan, Bryan P.-
dc.contributor.authorYu, Cheukman-
dc.contributor.authorLan, Huiyao-
dc.date.accessioned2014-07-26T23:10:55Z-
dc.date.available2014-07-26T23:10:55Z-
dc.date.issued2013-
dc.identifier.citationCardiovascular Research, 2013, v. 99, n. 4, p. 665-673-
dc.identifier.issn0008-6363-
dc.identifier.urihttp://hdl.handle.net/10722/199928-
dc.description.abstractAimsSmad7 plays a negative regulatory role in many inflammatory diseases, but its effect on hypertensive disease remains unknown. The present study tested the hypothesis that overexpression of Smad7 may have therapeutic potential for angiotensin II (Ang II)-mediated hypertensive cardiac remodelling.Methods and resultsHypertensive heart disease was induced in mice by subcutaneous infusion of Ang II for 28 days and treated with Smad7 by a non-invasive ultrasound-microbubble-mediated inducible Smad7 gene transfer. We found that cardiac Smad7 was largely reduced in the hypertensive heart and overexpression of cardiac Smad7 protected against the fall in the left ventricular (LV) ejection fraction (EF), an increase in LV mass, and cardiac inflammation and fibrosis such as up-regulation of pro-inflammatory cytokines (IL-1β, TNF-α) and fibrotic markers (collagen I, α-SMA), and infiltration of CD3+ T cells and F4/80+ macrophages. Further studies revealed that inactivation of the Sp1-TGF-β/Smad3-NF-κB (NF-κB, nuclear factor κB) pathways and prevention of cardiac miR-29 loss were mechanisms by which overexpression of Smad7 inhibited Ang II-mediated cardiac remodelling. Importantly, we also found that treatment with Smad7 when hypertensive cardiopathy established at day 14 halted the progression of cardiac injury by blunting the fall of EF and an increase in LV mass, and blocking TGF-β/Smad3-mediated cardiac fibrosis and NF-κB-driven inflammation.ConclusionSmad7 plays a protective role in Ang II-induced cardiac remodelling via mechanisms involving the Sp1-TGF-β/Smad-NF-κB-miR-29 regulatory network. Thus, Smad7 may be a novel therapeutic agent for hypertensive cardiovascular diseases. © 2013 The Author.-
dc.languageeng-
dc.relation.ispartofCardiovascular Research-
dc.subjectSmad7-
dc.subjectAng II-
dc.subjectFibrosis-
dc.subjectInflammation-
dc.subjectmiR-29-
dc.titleSmad7 inhibits angiotensin II-induced hypertensive cardiac remodelling-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/cvr/cvt151-
dc.identifier.pmid23761400-
dc.identifier.scopuseid_2-s2.0-84883239076-
dc.identifier.hkuros232088-
dc.identifier.volume99-
dc.identifier.issue4-
dc.identifier.spage665-
dc.identifier.epage673-
dc.identifier.eissn1755-3245-
dc.identifier.isiWOS:000323581900012-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats