ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of PTEN on Ang II induced cardiomyocyte hypertrophy and subsequent Ca(2+)/Calcineurin pathway changes.</p><p><b>METHODS</b>Primary cultured neonatal rat cardiomyocytes were cultured and were treated with phosphate-buffered saline, empty adenovirus (Ad-GFP), or adenovirus encoding for PTEN (Ad-PTEN-GFP) for 48 h and Ang II (10(-7) mol/L) was added to the medium for another 24 h. Cells were harvested and intracellular Ca(2+) concentration ([Ca(2+)] i) was determined by Fura-2/AM ratio imaging analysis; PTEN, ANF, beta-MHC and CaNAbeta mRNA evaluated with RT-PCR; PTEN and CaNAbeta protein by Western blot; CaN phosphatase activity by CaN detecting kits.</p><p><b>RESULTS</b>PTEN at mRNA and protein levels were significantly higher in Ad-PTEN-GFP treated cardiomyocytes than that of Ad-GFP treated cardiomyocytes. Ang II stimulation upregulated [Ca(2+)] i, CaNAbeta at mRNA and protein levels and CaN phosphatase activity in Ad-GFP treated cardiomyocytes but not in Ad-PTEN-GFP treated cardiomyocytes.</p><p><b>CONCLUSIONS</b>Cardiac hypertrophy induced by Ang II could be blocked by PTEN overexpression via suppressing Ca(2+)/Calcineurin pathway.</p>
Subject(s)
Animals , Rats , Adenoviridae , Genetics , Angiotensin II , Metabolism , Calcineurin , Metabolism , Calcium , Metabolism , Cardiomegaly , Metabolism , Cells, Cultured , DNA, Complementary , Myocytes, Cardiac , Metabolism , PTEN Phosphohydrolase , Genetics , Metabolism , RNA, Messenger , Metabolism , Rats, Wistar , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To investigate the alteration of expressions of beta(1)-, beta(2)-, beta(3)-adrenoceptor mRNA in human myocardial tissue and the relation between their expressions and cardiac function in patient with heart failure.</p><p><b>METHODS</b>The mRNA expressions of beta(1)-, beta(2)- and beta(3)-adrenergic receptors in myocardial tissue were analyzed by using the reverse transcriptase-polymerase chain reaction in 24 patients with heart failure of valvular heart disease and 5 control subjects.</p><p><b>RESULTS</b>Beta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects, and progressively reduced with aggravation of heart function. By contrast, beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls, and progressively elevated with aggravation of cardiac function. No difference was observed in beta(2)-adrenergic receptor among all groups.</p><p><b>CONCLUSION</b>The changes of beta-adrenergic receptor mRNA expression are associated with the severity of heart failure.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Case-Control Studies , Heart Failure , Genetics , Metabolism , RNA, Messenger , Metabolism , Receptors, Adrenergic, beta-1 , Genetics , Metabolism , Receptors, Adrenergic, beta-2 , Genetics , Metabolism , Receptors, Adrenergic, beta-3 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To examine the negative regulation role of PTEN in isoproterenol-induced cardiac hypertrophy by testing the expression of PTEN mRNA and protein and to explore the effects of captopril (Cap) on PTEN expression.</p><p><b>METHODS</b>Twenty four rats were randomly divided into three groups: control group, ISO group, and ISO+Cap group. The following parameters were examined:body weight (BW), heart weight (HW), left ventricular weight (LVW), left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and +/- dp/dt(max). The ratio of HW/BW and LVW/BW was calculated. PTEN mRNA and protein were tested by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>(1) Compared with the control group, the ratio of HW/BW and LVW/BW, LVEDP and LVESP were all increased in ISO group and ISO+Cap group (P < 0.05), but +/- dp/dt(max) was decreased (P < 0.05); (2) compared with the ISO group, the ratio of HW/BW and LVW/BW, LVEDP, LVESP were all decreased in ISO+Cap group (P < 0.05), but +/- dp/dt(max) was increased (P < 0.05); (3) compared with the control group, PTEN mRNA and protein were up-regulated in ISO group and ISO+Cap group; (4) compared with the ISO group, PTEN mRNA and protein were up-regulated in ISO+Cap group.</p><p><b>CONCLUSIONS</b>PTEN mRNA and protein are up-regulated in isoproterenol-induced cardiac hypertrophy. Captopril can up-regulate PTEN expression in cardiac hypertrophy. There is a negative regulative mechanism in cardiac hypertrophy process, in which PTEN is probably an endogenous negative regulator of cardiac hypertrophy.</p>