Document Detail

Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure.
MedLine Citation:
PMID:  17885560     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate whether the glycoprotein (gp130)-mediated survival pathway, which protects cardiomyocytes from apoptosis, is depressed in left ventricular hypertrophy hypertensive patients with chronic heart failure. METHODS: Transvenous endomyocardial biopsies were obtained in 52 hypertensive patients with left ventricular hypertrophy: 28 without heart failure and 24 with heart failure. gp130 and gp130-dependent antiapoptotic pathways p42/44 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) as well as gp130 agonist cardiotrophin-1 were analyzed by reverse transcriptase-polymerase chain reaction and western blot. Apoptosis was assessed by DNA end-labeling (TUNEL), caspase-3 immunostaining and caspase substrate poly(ADP-ribose) polymerase cleavage. RESULTS: gp130 protein expression (P < 0.05) and p42/44 MAPK and PI3K/Akt activation (P < 0.01) were decreased in heart-failure hypertensive patients compared with nonheart-failure hypertensive individuals. No changes in gp130 mRNA expression were found between the two groups. Cardiotrophin-1 was increased (P < 0.05) at both the mRNA and protein levels in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Cardiomyocyte apoptosis was increased (P < 0.01) in heart-failure hypertensive individuals compared with nonheart-failure hypertensive individuals. Inverse correlations (P < 0.01) occurred between cardiomyocyte apoptosis and p42/44 MAPK and PI3K/Akt activation in all hypertensive patients. Cardiotrophin-1 correlated inversely (r = -0.554, P < 0.05) with gp130 in all hypertensive individuals. In cultured HL-1 cardiomyocytes, cardiotrophin-1 decreased (P < 0.05) the gp130:phosphorylated gp130 (at Ser782) ratio and increased (P < 0.05) gp130ubiquitination. CONCLUSIONS: An association exists between depression of the gp130 cytoprotective pathway and stimulation of cardiomyocyte apoptosis in hypertensive patients that develop heart failure. Whether the excess of cardiotrophin-1 induces ligand-induced receptor down-regulation in these patients requires further study.
Arantxa González; Susana Ravassa; Iñigo Loperena; Begoña López; Javier Beaumont; Ramón Querejeta; Mariano Larman; Javier Díez
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  25     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-21     Completed Date:  2008-01-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  2148-57     Citation Subset:  IM    
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain.
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MeSH Terms
Aged, 80 and over
Case-Control Studies
Cytokine Receptor gp130 / genetics,  metabolism*
Cytokines / genetics,  metabolism
Heart Failure / etiology,  genetics,  metabolism*,  pathology*
Hypertension / complications,  genetics,  metabolism*,  pathology*
Hypertrophy, Left Ventricular / complications,  genetics,  metabolism,  pathology
Middle Aged
Myocytes, Cardiac / metabolism*,  pathology*
Signal Transduction
Reg. No./Substance:
0/Cytokines; 0/IL6ST protein, human; 0/cardiotrophin 1; 133483-10-0/Cytokine Receptor gp130
Comment In:
J Hypertens. 2007 Oct;25(10):2008-10   [PMID:  17885541 ]

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