| Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure. | |
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MedLine Citation:
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PMID: 17885560 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Arantxa González; Susana Ravassa; Iñigo Loperena; Begoña López; Javier Beaumont; Ramón Querejeta; Mariano Larman; Javier Díez |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 25 ISSN: 0263-6352 ISO Abbreviation: J. Hypertens. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-09-21 Completed Date: 2008-01-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 2148-57 Citation Subset: IM |
Affiliation:
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Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Apoptosis Case-Control Studies Cytokine Receptor gp130 / genetics, metabolism* Cytokines / genetics, metabolism Down-Regulation Female Heart Failure / etiology, genetics, metabolism*, pathology* Humans Hypertension / complications, genetics, metabolism*, pathology* Hypertrophy, Left Ventricular / complications, genetics, metabolism, pathology Male Middle Aged Myocytes, Cardiac / metabolism*, pathology* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/IL6ST protein, human; 0/cardiotrophin 1; 133483-10-0/Cytokine Receptor gp130 |
| Comments/Corrections | |
Comment In:
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J Hypertens. 2007 Oct;25(10):2008-10
[PMID:
17885541
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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