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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Cardiopatía hipertensiva > DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista >

Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure
Authors: Gonzalez, A. (Arantxa)
Ravassa, S. (Susana)
Loperena, I. (Iñigo)
Lopez, B. (Begoña)
Beaumont, J. (Javier)
Querejeta, R. (Ramón)
Larman, M. (Mariano)
Diez, J. (Javier)
Keywords: Cytokine Receptor gp130/metabolism
Heart Failure/metabolism
Heart Failure/pathology
Hypertension/metabolism
Hypertension/pathology
Myocytes, Cardiac/metabolism
Myocytes, Cardiac/pathology
Issue Date: 2007
Publisher: Lippincott, Williams & Wilkins
Publisher version: http://bit.ly/JN92Xe
ISSN: 1473-5598
Citation: Gonzalez A, Ravassa S, Loperena I, Lopez B, Beaumont J, Querejeta R, et al. Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure. J Hypertens 2007 Oct;25(10):2148-2157.
Abstract
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.
Permanent link: http://hdl.handle.net/10171/21863
Appears in Collections:DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista

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