Linked Life Data

20040887

Source:http://linkedlifedata.com/resource/pubmed/id/20040887

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-3-4
pubmed:abstractText
Restenosis after balloon angioplasty or stent placement is characterized by local accumulation of mainly vascular smooth muscle cells and the synthesis of extracellular matrix molecules (ECM).We hypothesized that inhibition of ECM synthesis represents a strategy to prevent trauma-induced neointima formation. Rats were treated with pirfenidone (1 g/kg of body weight orally.), an inhibitor of growth factor-induced collagen synthesis, and subjected to balloon denudation of the carotid artery. Two weeks later, computer-aided morphometry was done and compared with untreated controls (each n = 6). Neointimal proliferative activity was quantified immunohistochemically by counting PCNA-positive nuclei, and collagen deposition was visualized by picrosirius red staining and semi-quantified by Northern blot. Control-injured animals developed marked neointimal thickening within 2 weeks (I/M, mean intima to media ratio: 2.42 +/- 0.15) resulting in an 89.2% luminal narrowing. The neointima mainly consisted of vascular smooth muscle cells embedded in collagen. Neointima formation was strongly reduced when balloon-injured animals had been treated with pirfenidone (I/M ratio 0.22 +/- 0.08, P < 0.001), resulting in a minimal residual narrowing of the lumen (7.9%). I/M ratio did not further increase even after discontinuation of the drug for 14 days (0.35 +/- 0.13). Proliferative activity within the neointima was unaffected by the drug, 4.4% versus 4.8% of neointimal cells stained positive for PCNA in carotid arteries of treated versus untreated animals, respectively. However, picrosirius red staining demonstrated marked attenuation of collagen deposition, a finding that was further confirmed by Northern blot of homogenized vessels. Pirfenidone, currently being investigated clinically for the treatment of various fibrotic diseases, is able to prevent neointimal lesion formation most likely through inhibition of local ECM deposition. Targeting matrix deposition may have an intriguing potential for the prevention of vascular proliferative diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1533-4023
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Inhibition of matrix deposition: a new strategy for prevention of restenosis after balloon angioplasty.
pubmed:affiliation
Department of Cardiology, Giessen University, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't