| Objective:Cardiotrophin-1(CT-1), a new member of interleukin-6 cytokine family, recently was identified to having the effect of inducing cardiomyocyte hypertrophy, in this study we investigated the role of CT-1 in the hypertensive ventricular remodeling, the relationship between CT-1 and renin angiotensin system(RAS) as well as if CT-1 was involved in the mechanism of fluvastatin preventing hypertensive ventricular remodeling Methods: (1) 3-4 passages cardiac fibroblasts were cultured in vitro, and divided into four groups: group C (Control); group H: cultured under high hydrostatic pressure (160mmHg); group ASOND: interfered with CT-1 anti-sense oligodeoxynucleotides (10μM); group SODN: incubated with CT-1 sense oligodeoxynucleotides (10μM). Cell proliferation was quantified by MTT. AngⅡ concentration in the conditioned mediums was measured by radioimmunoassay (RIA), the expression of CT-1 was detected by western blotting. (2) The chronic L-NAME treatment-induced hypertensive rats were divided into four groups : group C(Control); group L: treated with L-NAME (50mg/kg/d). group L+S and group L+C: interfered with fluvastatin 5mg/kg/d or captopril 50mg/kg/d after four weeks. The rats were sacrified after 12 weeks, the ventricular morphometry was analyzed, the content of AngⅡ and hydroxyproline of myocardiac tissue were detected , and using western blotting to examine the expression of CT-1. Results: in vitro: (1) High hydrostatic pressure stimulated the proliferation of cardiac fibroblasts(0.153±0.011 vs 0.114±0.012, p<0.01),increased the secretion of AngⅡ (21.47±1.37 vs 17.86±0.64 pg/mg, p<0.01),upregulated the expression of CT-1(1.56±0.24 vs 0.95±0.19, p<0.05) (2) CT-1 anti-sense oligodeoxynucleotide inhibited the proliferation of cardiac fibroblasts(0.132±0.13 vs 0.153±0.11,p<0.05), the secretion of AngⅡ (19.12±0.91 vs 21.47±1.37 p<0.05), and the production of CT-1 induced by high hydrostatic pressure (1.03±0.21 vs 1.56±0.24 p<0.05). but CT-1 sense oligodeoxynucleotide had... |
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