Linked Life Data

12907417

Source:http://linkedlifedata.com/resource/pubmed/id/12907417

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Abnormal regulation of apoptosis is observed in ischemic injury and may contribute to the pathogenesis of atherosclerosis. However, its role in cardiac allograft vasculopathy (CAV), the fundamental lesion of chronic rejection (CR) in heart transplantation, remains uncertain. To clarify this issue, apoptosis was quantitated in myocardium and coronary arteries from 5 cardiac allograft donors (NL) and explanted hearts of 24 patients with ischemic cardiomyopathy (IsCM) and 15 patients with CR. Tissue samples were analyzed via end-labeling fragmented DNA [via deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)] and immunoblotting for activated caspase-3 and -9. Myocyte apoptosis assessed by TUNEL was similarly increased over NL (0.21%) in both the CR (0.88%; P < 0.01) and IsCM (0.88%; P < 0.01) groups. Activated caspase-9 levels were significantly higher in CR (14.7%) compared with IsCM (6.9%; P < 0.01) and NL (0%) groups, whereas activated caspase-3 levels were similarly elevated in both CR and IsCM (7.8 and 6.5% vs. 0% in NL; P < 0.01 and P < 0.05) groups. Expression of myocardial Bcl-2 and Bax was increased in CR compared with both NL (Bax, 4.3-fold; P < 0.01; Bcl-2, 5.9-fold; P < 0.01) and IsCM (IsCM: Bax, 2.2-fold; P < 0.05; Bcl-2, 3.2-fold; P < 0.01) groups. The rate of apoptosis and the Bcl-2/Bax ratio independently correlated to graft survival in CR (activation of caspase-9: r = 0.87; P < 0.01; Bcl-2/Bax: r = 0.57; P = 0.05). Compared with native atherosclerosis, coronary arteries with CAV showed more medial apoptosis (7.8-fold; P < 0.01) and higher Bcl-2 levels (5.1-fold; P < 0.01) with lower Bax levels (threefold; P < 0.05) in the intima. These results indicate that abnormal Bcl-2 and Bax expression in myocardium and coronary arteries of cardiac allografts with CR is distinct from that in IsCM and suggest that balancing Bcl-2 to Bax in transplanted hearts promotes long-term graft survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2832-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12907417-Adolescent, pubmed-meshheading:12907417-Adult, pubmed-meshheading:12907417-Aged, pubmed-meshheading:12907417-Cardiomyopathies, pubmed-meshheading:12907417-Caspase 3, pubmed-meshheading:12907417-Caspases, pubmed-meshheading:12907417-Child, pubmed-meshheading:12907417-Coronary Artery Disease, pubmed-meshheading:12907417-DNA Fragmentation, pubmed-meshheading:12907417-Female, pubmed-meshheading:12907417-Graft Survival, pubmed-meshheading:12907417-Heart Transplantation, pubmed-meshheading:12907417-Humans, pubmed-meshheading:12907417-Immunoblotting, pubmed-meshheading:12907417-Immunohistochemistry, pubmed-meshheading:12907417-Male, pubmed-meshheading:12907417-Middle Aged, pubmed-meshheading:12907417-Mitochondria, pubmed-meshheading:12907417-Proto-Oncogene Proteins, pubmed-meshheading:12907417-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12907417-Transplantation, Homologous, pubmed-meshheading:12907417-bcl-2-Associated X Protein, pubmed-meshheading:12907417-bcl-X Protein
pubmed:year
2003
pubmed:articleTitle
Balanced expression of mitochondrial apoptosis regulatory proteins correlates with long-term survival of cardiac allografts.
pubmed:affiliation
Division of Cardiothoracic Surgery, Department of Surgery, University of California at Los Angeles Medical Center, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't