Linked Life Data

21215756

Source:http://linkedlifedata.com/resource/pubmed/id/21215756

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-7
pubmed:abstractText
The aim of the study is to characterize the signal transduction leading to interstitial fibrosis in the pathogenesis of atrial fibrillation (AF) and atrial remodeling. Samples of the left atrial appendage (LA) from patients with AF showed higher collagen content (73 ± 5 vs. 38 ± 2 ?g/mg protein) and 2.5-fold increased collagen crosslinking compared to patients with sinus rhythm (SR). Affymetrix-assays, RT-PCR and western Blot analysis revealed that LA of AF patients are characterized by increased lysyl oxidase (LOX) mRNA (218 ± 42%) and protein (253 ± 11%) expression. This was associated with increased expression of connective tissue growth factor (CTGF), fibronectin and Rac1 activity compared to SR. In neonatal cardiac fibroblasts, the Rac1 specific small molecule inhibitor NSC23766 prevented angiotensin II (AngII) induced upregulation of LOX (214 ± 16%) expression. Inhibition of CTGF by siRNA transfections completely inhibited AngII induced LOX expression. The LOX specific small molecule inhibitor BAPN prevented AngII and CTGF induced fibronectin expression. Left atria of transgenic mice with cardiac overexpression of Rac1 (RacET) that develop AF at high age exhibited upregulation of CTGF as well as LOX (187 ± 7%) and fibronectin (627 ± 146%) expression. Atria of RacET showed increased collagen content (28 ± 2 ?g/mg protein) and crosslinking (10 ± 0.7) compared to wildtypes (20 ± 0.4 ?g/mg protein; 5 ± 0.9). Left atrial myocardium of patients with atrial fibrillation is characterized by increased lysyl oxidase and fibronectin expression as well as collagen cross-linking. In cardiac fibroblasts, Rac1 GTPase mediates upregulation of fibronectin via LOX and CTGF. Inhibition of this signaling pathway may therefore represent a target for the prevention of fibrotic atrial remodeling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1095-8584
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
678-85
pubmed:meshHeading
pubmed-meshheading:21215756-Aged, pubmed-meshheading:21215756-Angiotensin II, pubmed-meshheading:21215756-Animals, pubmed-meshheading:21215756-Animals, Newborn, pubmed-meshheading:21215756-Atrial Fibrillation, pubmed-meshheading:21215756-Blotting, Western, pubmed-meshheading:21215756-Cells, Cultured, pubmed-meshheading:21215756-Collagen, pubmed-meshheading:21215756-Connective Tissue Growth Factor, pubmed-meshheading:21215756-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21215756-Female, pubmed-meshheading:21215756-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:21215756-Heart Atria, pubmed-meshheading:21215756-Humans, pubmed-meshheading:21215756-Immunohistochemistry, pubmed-meshheading:21215756-Male, pubmed-meshheading:21215756-Mice, pubmed-meshheading:21215756-Myocytes, Cardiac, pubmed-meshheading:21215756-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:21215756-Protein-Lysine 6-Oxidase, pubmed-meshheading:21215756-Rats, pubmed-meshheading:21215756-Rats, Sprague-Dawley, pubmed-meshheading:21215756-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21215756-rac1 GTP-Binding Protein
pubmed:year
2011
pubmed:articleTitle
Increased lysyl oxidase expression and collagen cross-linking during atrial fibrillation.
pubmed:affiliation
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. oliver.adam@uks.eu
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't