Key result
In hypertensive patients with left ventricular hypertrophy, heart failure was associated with decreased gp130 protein expression (P<0.05) and increased cardiomyocyte apoptosis (P<0.01).
Observational (n=52)
p-value: p=<0.05
In hypertensive patients with left ventricular hypertrophy, the development of heart failure is associated with depression of the gp130 cytoprotective pathway and increased cardiomyocyte apoptosis.
Hypothesis-generating for gp130 pathway in hypertensive LVH progression; should not change practice without prospective validation.
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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González et al. (2007) conducted an observational in Hypertensive patients with left ventricular hypertrophy (n=52). Heart failure vs. Non-heart-failure hypertensive individuals was evaluated on gp130 protein expression and cardiomyocyte apoptosis (p=<0.05). In hypertensive patients with left ventricular hypertrophy, heart failure was associated with decreased gp130 protein expression (P<0.05) and increased cardiomyocyte apoptosis (P<0.01).
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