ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of rosiglitazone (RSG, the activator of peroxisome proliferators activated receptor lambda) for inhibiting endothelin-1 (ET-1)-induced neonatal rat cardiac myocyte hypertrophy and the role of protein kinase C (PKC) and c-fos.</p><p><b>METHODS</b>In vitro cultured neonatal rat cardiac myocytes were treated with ET-1, phorbol ester (PMA, the PKC activator), ET-1+RSG, ET-1+chelerythrine (che, the PKC inhibitor), PMA+RSG, or without treatment (control), respectively. The effects of RSG on the protein content, (3)H-leucine incorporation, PKC activity and C-fos protein expression were observed in the cardiac myocytes stimulated with ET-1 or PMA.</p><p><b>RESULTS</b>After two days of culture, the intracellular protein content in ET-1 group and PMA group were increased by 15% (339-/+15 microg/ml) and 13% (329-/+14 microg/ml) as compared with the control cells (290-/+13 microg/ml), respectively (P<0.01). Compared with the ET-1 group, cells treated with ET-1+10(-8) mol/L RSG, ET-1+10(-7) mol/L RSG, and ET-1+che showed decreased intracellular protein content by 10% (303-/+14 microg/ml, P<0.05), 12% (292-/+11 microg/ml, P<0.05), and 13% (291-/+12 microg/ml, P<0.01), respectively. The intracellular protein content in PMA+10(-7) mol/LRSG group was decreased by 10% (P<0.05) in comparison with the PMA group. RSG inhibited protein synthesis enhancement and increased (3)H-leucine incorporation induced by ET-1 and PMA, and antagonized the effects of ET-1 and PMA in promoting PKC activity and c-fos protein expression in the myocytes.</p><p><b>CONCLUSION</b>The inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.</p>
Subject(s)
Animals , Rats , Animals, Newborn , Blotting, Western , Cell Enlargement , Cells, Cultured , Dose-Response Relationship, Drug , Endothelin-1 , Pharmacology , Hypoglycemic Agents , Pharmacology , Myocytes, Cardiac , Cell Biology , Metabolism , Protein Kinase C , Metabolism , Proto-Oncogene Proteins c-fos , Rats, Sprague-Dawley , Signal Transduction , Tetradecanoylphorbol Acetate , Pharmacology , Thiazolidinediones , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To observe the relationship between protein sythesis and cardiomyocyte viability in neonatal rats.</p><p><b>METHODS</b>The protein sythesis in neonatal rat cardiomyocytes was measured according to Brandford's method, the absorbance at 490 nm (A(490 nm)) of the cells was measured with MTT assay and the cell viability evaluated by the ratio of A(490 nm) to the total cell number.</p><p><b>RESULTS</b>ET-1 increased cardiomyocyte protein synthesis dose-dependently, and this effect was attenuated by the application of lacidipine and tetramethylpyrazines Higher doses of ET-1 resulted in lower A(490 nm)/total cell number ratio, which was further lowered by larcidipine and tetramethylpyrazine.</p><p><b>CONCLUSION</b>The status of protein synthesis is not associated with the viability of neonatal rat cardiomyocytes.</p>
Subject(s)
Animals , Rats , Animals, Newborn , Calcium Channel Blockers , Pharmacology , Cell Survival , Cells, Cultured , Dihydropyridines , Pharmacology , Dose-Response Relationship, Drug , Endothelin-1 , Pharmacology , Myocytes, Cardiac , Cell Biology , Metabolism , Protein Biosynthesis , Pyrazines , Pharmacology , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To compare the prognostic value of regional longitudinal ventricular systolic velocities with that of maximal oxygen consumption (VO(2max)) in patients with dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>VO(2max) derived from cardiopulmonary exercise tests and regional longitudinal ventricular systolic velocities obtained from tissue Doppler imaging were compared in 18 DCM patients with cardiac events (death, cardiac transplantation, hospitalization, group A) and 24 patients without cardiac events (group B). Peak velocities during isovolumic contraction (is) and ejection (ez) were interrogated at the mitral or tricuspid annulus (site 1), at the mid parts of the walls (site 3, at the level of papillary muscle), and at the midpoints (site 2) between sites 1 and 3 of interventricular septum (S), lateral wall of LV (L) and of RV (R) in apical 4 chambers view.</p><p><b>RESULTS</b>R1is, R2is, R2ez, R3is, S1is, S1ez, S2ez, L1is, L1ez and L2ez of group A were significantly lower than those in group B (all P < 0.05). Independent of VO(2max), high sensitivity and specificity were shown for R3ez, S1ez, L1ez, L1is, L2is and L3is in predicting cardiac events of DCM patients.</p><p><b>CONCLUSION</b>LV and RV systolic velocities could independently predict cardiac events in DCM patients.</p>