Publications (26)53.03 Total impact
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Article: High risk subgroups of early repolarization pattern, the basis of cardiac electrophysiologic instable and potential vulnerability to ventricular fibrillation?
Journal of the American College of Cardiology 03/2013; · 14.16 Impact Factor -
Article: Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension.
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ABSTRACT: Circulating endothelial progenitor cells (EPCs) are reduced in hypertension, which inversely correlates with its mortality. Deoxycorticosterone acetate (DOCA)-salt hypertension features elevated endothelin (ET) 1 and oxidative stress. We tested the hypothesis that ET-1 induces EPC dysfunction by elevating oxidative stress through the ET(A)/NADPH oxidase pathway in salt-sensitive hypertension. Both ET(A) and ET(B) receptors were expressed in EPCs, but only ET(A) receptors were significantly increased in EPCs of DOCA-salt rats. EPC number and function were reduced in DOCA-salt rats compared with sham controls, and both were reversed by in vivo blockade of ET(A) receptors or NADPH oxidase. The enzymatic activities of NAPDH oxidase and its subunits gp91(phox), p22(phox), and Rac1 were augmented in EPCs of DOCA-salt rats, with concomitantly decreased antioxidant enzymes manganese superoxide dismutase, copper-zinc superoxide dismutase, and glutathione peroxidase 1. Reactive oxygen species level was elevated in EPCs from DOCA-salt rats, accompanied by increased EPC telomerase inactivation, senescence, and apoptosis, which were rescued by ET(A) or NADPH oxidase blockade. Cell therapy of normal or treated DOCA EPCs, but not untreated DOCA EPCs, significantly increased capillary density and blood perfusion in ischemic hindlimbs of DOCA-salt rats. p53 and Bax/Bcl-2 ratios were increased in EPCs of DOCA-salt rats, which were reversed by ET(A) antagonist, NADPH oxidase inhibitor, or polyethylene glycol-superoxide dismutase. Finally, in ET(B)-deficient rats, plasma ET-1 was elevated, and EPC number and telomerase activity were diminished. These results demonstrate, for the first time, that both ET-1 activation of ET(A)/NADPH oxidase pathway and diminished antioxidants critically contribute to EPC reduction and dysfunction via increased oxidative stress in salt-sensitive hypertension.Hypertension 03/2012; 59(5):1037-43. · 6.21 Impact Factor -
Article: Effects of insulin-like growth factor-1 on the properties of mesenchymal stem cells in vitro.
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ABSTRACT: To explore the effects of insulin-like growth factor-1 (IGF-1) on migration, proliferation and differentiation of mesenchymal stem cells (MSCs). MSCs were obtained from Sprague-Dawley rats by a combination of gradient centrifugation and cell culture techniques and treated with IGF-1 at concentrations of 5-20 ng/ml. Proliferation of MSCs was determined as the mean doubling time. Expression of CXC chemokine receptor 4 (CXCR4) and migration property were determined by flow cytometry and transwell migration essay, respectively. mRNA expression of GATA-4 and collagen II was determined by reverse transcription-polymerase chain reaction (RT-PCR). The mean doubling time of MSC proliferation was decreased, and the expression of CXCR4 on MSCs and migration of MSCs were increased by IGF-1, all in a dose-dependent manner, while the optimal concentration of IGF-1 on proliferation and migration was different. IGF-1 did not affect the expression of GATA-4 or collagen II mRNA. IGF-1 dose-dependently stimulated the proliferation of MSCs, upregulated the expression of CXCR4, and accelerated migration. There was no apparent differentiation of MSCs to cardiomyocytes or chondrocytes after culturing with IGF-1 alone.Journal of Zhejiang University SCIENCE B 01/2012; 13(1):20-8. · 1.10 Impact Factor -
Article: [Effects of AMPK on the transcriptional activity of FOXO1 and ubiquitin ligase MuRF1 expression in rat cardiomyocytes].
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ABSTRACT: To investigate the effects of AICAR on the activity of transcription factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes, and explore the possible role of AMP-activated protein kinase (AMPK) in proteolysis pathways. In vitro cultured neonatal rat cardiac myocytes were treated with AICAR, and Western blotting was used to detect the phosphorylation of FOXO1 and expression of MuRF1 in the cells. AICAR activated AMPK in rat cardiac myocytes. Activated AMPK significantly inhibited the phosphorylation of FOXO1 and increased MuRF1 protein expression. AMPK may regulate proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1 expression.Nan fang yi ke da xue xue bao = Journal of Southern Medical University 11/2010; 30(11):2419-22. -
Article: Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats.
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ABSTRACT: 1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent studies suggest that pharmacological activation of AMPK inhibits cardiac hypertrophy. In the present study, we examined whether long-term treatment with metformin could attenuate ventricular hypertrophy in a rat model. The potential involvement of nitric oxide (NO) in the effects of metformin was also investigated. 2. Ventricular hypertrophy was established in rats by transaortic constriction (TAC). Starting 1 week after the TAC procedure, rats were treated with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were used to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10⁻⁶ mol/L) for 24 h under serum-free conditions in the presence or absence of metformin (10⁻³ mol/L), compound C (10⁻⁶ mol/L), L-NAME (10⁻⁶ mol/L) or their combination. The rate of incorporation of [³H]-leucine was determined, western blotting analyses of AMPK-eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were undertaken and the concentration of NO in culture media was determined. 4. Transaortic constriction resulted in significant haemodynamic dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident. Treatment with metformin improved haemodynamic function and significantly attenuated ventricular hypertrophy. Most of the effects of metformin were abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on haemodynamic function and ventricular hypertrophy in TAC rats. 5. In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME. The improvement in cardiac structure and function following metformin treatment was associated with enhanced phosphorylation of AMPK and eNOS and increased NO production. 6. The findings of the present study indicate that long-term treatment with metformin could attenuate ventricular hypertrophy induced by pressure overload via activation of AMPK and a downstream signalling pathway involving eNOS-NO.Clinical and Experimental Pharmacology and Physiology 11/2010; 38(1):55-62. · 1.85 Impact Factor -
Article: The nonpeptide AVE0991 attenuates myocardial hypertrophy as induced by angiotensin II through downregulation of transforming growth factor-beta1/Smad2 expression.
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ABSTRACT: The nonpeptide AVE0991 is expected to be a putative new drug for cardiovascular diseases. However, the mechanisms for the cardioprotective actions of AVE0991 are still not fully understood. We planned to determine whether AVE0991 attenuates the angiotensin II (AngII)-induced myocardial hypertrophy and whether these AVE0991 effects involved transforming growth factor beta1 (TGF-beta1) and Smad2. A rat model of neonatal myocardial hypertrophy was induced by AngII. The AngII group significantly increased in protein content, surface area, and [(3)H]leucine incorporation efficiency by cardiomyocytes, compared to those of the control group (P < 0.01). The AngII group also had elevated TGF-beta1 and Smad2 expression (P < 0.01). These AngII-induced changes were significantly attenuated by AVE0991 in a dose-dependent manner. In our study, these actions of AngII (10(-6) mol/l) were significantly inhibited by both concentrations of AVE0991 (10(-5) mol/l and 10(-7) mol/l). Moreover, the high AVE0991 group had significantly better inhibition of myocardial hypertrophy than the low AVE0991 group. Meanwhile, the beneficial effects of AVE0991 were completely abolished when the cardiomyocytes were pretreated with Ang-(1-7) receptor antagonist A-779 (10(-6) mol/l). These results suggested that AVE0991 prevented AngII-inducing myocardial hypertrophy in a dose-dependent fashion, a process that may be associated with the inhibition of TGF-beta1/Smad2 signaling.Heart and Vessels 09/2010; 25(5):438-43. · 2.05 Impact Factor -
Article: Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro.
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ABSTRACT: To examine the inhibitory effects of adenosine monophosphate-activated protein kinase (AMPK) activation on cardiac hypertrophy in vitro and to investigate the underlying molecular mechanisms. Cultured neonatal rat cardiomyocytes were treated with the specific AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the specific AMPK antagonist Compound C, and then stimulated with phenylephrine (PE). The Muscle RING finger 1 (MuRF1)-small interfering RNA (siRNA) was transfected into cardiomyocytes using Lipofectamine 2000. The surface area of cultured cardiomyocytes was measured using planimetry. The protein degradation was determined using high performance liquid chromatography (HPLC). The expression of beta-myosin heavy chain (beta-MHC) and MuRF1, as well as the phosphorylation levels of AMPK and Forkhead box O 1 (FOXO1), were separately measured using Western blot or real-time polymerase chain reaction. Activation of AMPK by AICAR 0.5 mmol/L inhibited PE-induced increase in cardiomyocyte area and beta-MHC protein expression and PE-induced decrease in protein degradation. Furthermore, AMPK activation increased the activity of transcription factor FOXO1 and up-regulated downstream atrogene MuRF1 mRNA and protein expression. Treatment of hypertrophied cardiomyocytes with Compound C 1 micromol/L blunted the effects of AMPK on cardiomyocyte hypertrophy and changes to the FOXO1/MuRF1 pathway. The effects of AICAR on cardiomyocyte hypertrophy were also blocked after MuRF1 was silenced by transfection of cardiomyocytes with MuRF1-siRNA. The present study demonstrates that AMPK activation attenuates cardiomyocyte hypertrophy by modulating the atrophy-related FOXO1/MuRF1 signaling pathway in vitro.Acta Pharmacologica Sinica 07/2010; 31(7):798-804. · 1.95 Impact Factor -
Article: Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways.
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ABSTRACT: Increased oxidative stress has been associated with the pathogenesis of chronic cardiac hypertrophy and heart failure. Since allicin suppresses oxidative stress in vitro and in vivo, we hypothesized that allicin would inhibit cardiac hypertrophy through blocking oxidative stress-dependent signaling. We examined this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. Our results showed that allicin markedly inhibited hypertrophic responses induced by Ang II or pressure overload. The increased reactive oxygen species (ROS) generation and NADPH oxidase activity were significantly suppressed by allicin. Our further investigation revealed this inhibitory effect on cardiac hypertrophy was mediated by blocking the activation of ROS-dependent ERK1/2, JNK1/2 and AKT signaling pathways. Additional experiments demonstrated allicin abrogated inflammation and fibrosis by blocking the activation of nuclear factor-κB and Smad 2/3 signaling, respectively. The combination of these effects resulted in preserved cardiac function in response to cardiac stimuli. Consequently, these findings indicated that allicin protected cardiac function and prevented the development of cardiac hypertrophy through ROS-dependent mechanism involving multiple intracellular signaling.The Journal of nutritional biochemistry 02/2010; 21(12):1238-50. · 4.29 Impact Factor -
Article: Rosiglitazone‐induced myocardial protection against ischaemia–reperfusion injury is mediated via a phosphatidylinositol 3‐kinase/Akt‐dependent pathway
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ABSTRACT: Summary1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor γ ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia–reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury.2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3α signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated.3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3α in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone.4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3α-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3α-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury.Clinical and Experimental Pharmacology and Physiology 01/2010; 37(2):156 - 161. · 1.85 Impact Factor -
Article: [Role of liver X receptors on cardiomyocyte hypertrophy].
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ABSTRACT: To investigate the expression of liver X receptors (LXR) in hypertrophic myocardium and the effect of LXR agonist T0901317 on angiotensin II (AngII) induced cardiomyocyte hypertrophy. Transverse aortic coarctation (TAC) or sham operation were performed in 2-month-old wide type mice (C57/B6). Two weeks later, the expression of LXR in myocardium was detected by quantitative real-time PCR analysis and Western blot analysis. The effect of LXR agonist T0901317 on AngII-induced hypertrophy in cultured neonatal rat cardiomyocytes was also assessed. Quantitative real-time PCR analysis and Western blot analysis showed that LXRalpha but not LXRbeta expression was upregulated post TAC both at mRNA and protein levels (All P < 0.05). AngII induced increased [(3)H] leucine incorporation and cardiomyocyte hypertrophy were significantly reduced by T0901317 in a dose-dependent manner (P < 0.05). T0901317 also dose-dependently inhibited atrial natriuretic peptide (ANP) gene expression in cardiomyocytes (P < 0.05). Our findings strongly suggest that LXR is a potent mediator of cardiomyocyte hypertrophy and LXR activation could attenuate AngII induced cardiomyocyte hypertrophy in vitro.Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 12/2009; 37(12):1119-23. -
Article: Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-alpha signaling pathway.
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ABSTRACT: The activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy, however, the mechanism remains unclear. Rat models of cardiac hypertrophy were created with transaortic constriction (TAC) to investigate the mechanistic role of AMPK involved. RT-PCR and Western blot analyses indicated that hypertrophy marker genes ANP and beta-MHC expression were up-regulated in the myocardium of TAC rats. We also observed that the expressions of peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes, carnitine palmitoyl transferase-capital I, Ukrainian (CPT-capital I, Ukrainian) and medium-chain acyl-COA dehydrogenases (MCAD), were down-regulated, and the fatty acid oxidation was decreased in TAC rats. Treatment of TAC animals with 5-aminoimidazole 1 carboxamide ribonucleoside (AICAR, 0.5 mg/g body wt), a specific activator of AMPK, inhibited cardiac hypertrophy in TAC and reversed PPARalpha, CPT-I and MCAD expression and fatty acid oxidation. Similar observations were made in hypertrophied cardiomyocytes induced by phenylephrine in vitro. Treatment of hypertrophied cardiomyocytes with Compound C, a specific AMPK inhibitor, showed an effect opposite to that of AICAR. The effect of AICAR on cardiac hypertrophy was blocked after PPARalpha was silenced by transfection of cardiomyocytes with PPARalpha-siRNA. Luciferase activity assay suggested that AICAR elevates PPARalpha transcriptional activity. These results indicate that AMPK plays an important role in the inhibition of cardiac hypertrophy by activating the PPARalpha signaling pathway.European journal of pharmacology 09/2009; 620(1-3):63-70. · 2.59 Impact Factor -
Article: B-type natriuretic peptide attenuates cardiac hypertrophy via the transforming growth factor-ß1/smad7 pathway in vivo and in vitro.
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ABSTRACT: 1. Previously, we showed that long-term treatment of rats after myocardial infarction (MI) with B-type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long-term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long-term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved. 2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 microg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10(-6) mol/L angiotensin (Ang) II for 48 h and cell surface area and [(3)H] incorporation were measured. Transforming growth factor (TGF)-beta1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription-polymerase chain reaction and western blotting. 3. Long-term BNP treatment dose-dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF-beta1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF-beta1/smad7 pathway, which were completely blocked by the cyclic GMP-dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10(-6) mol/L KT5823 for 48 h). 4. The results of the present study demonstrate that long-term treatment of rats with BNP dose-dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF-beta1 and upregulation of smad7 via PKG signalling. Long-term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.Clinical and Experimental Pharmacology and Physiology 09/2009; 37(3):283-9. · 1.85 Impact Factor -
Article: Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway.
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ABSTRACT: 1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor gamma ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia-reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury. 2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3alpha signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated. 3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3alpha in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone. 4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3alpha-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3alpha-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury.Clinical and Experimental Pharmacology and Physiology 07/2009; 37(2):156-61. · 1.85 Impact Factor -
Article: [Side effects of non-steroidal anti-inflammatory drugs on gastric mucosa and preventive effects of teprenone].
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ABSTRACT: To evaluate the side effects of non-steroidal anti-inflammatory drugs (NSAID) on gastric mucosa, and to study the preventive effects of teprenone in patients. 108 patients taking NSAID for more than 3 months with no infection of helicobacter pylori (Hp) were collected. All patients were screened by endoscopy and their upper gastrointestinal symptoms were evaluated. Then, 16 patients with ulcers were excluded and 92 patients were randomly divided into intervention group with teprenone and control group. After follow-up for 3 months, patients were screened again by endoscopy and their upper gastrointestinal symptoms were also evaluated. Specimens of gastric mucosa were studied by PAS dyeing, and Cyclooxygenase (COX) level were evaluated by immunohistochemical technique. Of patients taking NSAIDs, the erosion was found in 48 (44.4%) patients while 16 (14.8%) were found with peptic ulcers. The damages were improved significantly (Z = -4.96, P = 0.000) in the intervention group with teprenone (n = 45) as compared with control group (n = 47) after follow-up for 3 months. Both the cox-1 level [31.1% (14/45) vs 6.7% (3/45), P = 0.003] and mucus thickness [66.7% (30/45) vs 13.3% (6/45), P= 0.000] also increased in the intervention group as compared with control group. No significant difference was found on COX-2 level between these two groups [28.9% (13/45) vs 31.1% (14/45), P = 0.82]. Long-term use of NSAID caused severe damages on gastric and duodenal mucosa; teprenone improved NSAID-related gastric side effects and increased the COX-1 level and mucus thickness.Zhonghua yi xue za zhi 05/2009; 89(16):1122-5. -
Article: Epigallocatechin-3-gallate attenuates cardiac hypertrophy in hypertensive rats in part by modulation of mitogen-activated protein kinase signals.
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ABSTRACT: 1. It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2. In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3. The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and β-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52% vs TAC, respectively), accompanied by significant inhibition of nuclear factor-κB and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats.Clinical and Experimental Pharmacology and Physiology 04/2009; 36(9):925-32. · 1.85 Impact Factor -
Article: EPIGALLOCATECHIN‐3‐GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN‐ACTIVATED PROTEIN KINASE SIGNALS
Clinical and Experimental Pharmacology and Physiology 03/2009; 36(9):925 - 932. · 1.85 Impact Factor -
Article: [Role of nuclear factor-KappaB in endothelial injury in acute myocardial infarction].
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ABSTRACT: To examine the change in nuclear factor-KappaB (NF-KappaB) activity, tumor necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin (sTM) levels at different time following reperfusion in acute myocardial infarction (AMI), and to identify the role of ischemia/reperfusion after ischemia in injury to endothelial cells and its relevant mechanism. AMI group included 8 randomly selected patients with AMI, and a normal control group (n=8) composing individuals who underwent health check. NF-KappaB activity in monocytes was determined by electrophoretic mobility shift assays (EMSA). The level of TNF-alpha was measured by radio-immunity and sTM was measured by enzyme linked immunosorbent assay (ELISA). The NF-KappaB activity, TNF-alpha and sTM levels raised dramatically at 0.5 hour after reperfusion, reaching peak at 1 hour and declined gradually at 3, 12 and 24 hours. The levels of all the determined parameters at every time point were significantly higher than that of normal control group, and their levels at 1 hour were significantly higher than that at 24 hours (all P<0.05). There was a positive correlation between the NF-KappaB activity and the levels of TNF-alpha and sTM (all P<0.05). These results indicate that NF-KappaB is activated and the levels of TNF-alpha and sTM rise significantly after reperfusion in AMI. The activation of NF-KappaB maybe one of the most important pathogenic mechanism of endothelial injury.Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 07/2008; 20(7):413-5. -
Article: Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy.
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ABSTRACT: Recent in vitro studies suggest that adenosine monophosphate (AMP)-activated protein kinase (AMPK) exerts inhibitory effects on cardiac hypertrophy. However, it is unclear whether long-term activation of AMPK will affect cardiac hypertrophy in vivo. In these reports, we investigate the in vivo effects of long-term AMPK activation on cardiac hypertrophy and the related molecular mechanisms. To examine the effects of AMPK activation in the development of pressure overload-induced cardiac hypertrophy, we administered 5-aminoimidazole 1 carboxamide ribonucleoside (AICAR, 0.5 mg/g body wt), a specific activator of AMPK, to rats with transaortic constriction (TAC) for 7 weeks. We found that long-term AMPK activation attenuated cardiac hypertrophy, and improved cardiac function in rats subjected to TAC. Furthermore, long-term AMPK activation attenuated protein synthesis, diminished calcineurin-nuclear factor of activated T cells (NFAT) and nuclear factor kappaB (NF-kappaB) signaling in pressure overload-induced hypertrophic hearts. Our in vitro experiments further proved that activation of AMPK by infection of AdAMPK blocked cardiac hypertrophy and NFAT, NF-kappaB, and MAPK signal pathways. The present study demonstrates for the first time that pharmacological activation of AMPK inhibits cardiac hypertrophy in through blocking signaling transduction pathways that are involved in cardiac growth. It presents a potential therapy strategy to inhibit pathological cardiac hypertrophy by increasing the activity of AMPK.Journal of Cellular Biochemistry 05/2007; 100(5):1086-99. · 2.87 Impact Factor -
Article: PPARgamma phosphorylation mediated by JNK MAPK: a potential role in macrophage-derived foam cell formation.
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ABSTRACT: To investigate whether oxidized low-density lipoprotein (ox-LDL) modulates peroxisome proliferator-activated receptor gamma (PPARgamma) activity through phosphorylation in macrophages, and the effect of PPARgamma phosphorylation on macrophages-derived foam cell formation. After exposing the cultured THP-1 cells to ox-LDL in the presence or absence of different mitogen-activated protein kinase (MAPK) inhibitors, PPARgamma and phosphorylated PPARgamma protein levels were detected by Western blot. MAPK activity was analyzed using MAP Kinase Assay Kit. Intracellular cholesterol accumulation was assessed by Oil red O staining and cholesterol oxidase enzymatic method. The mRNA level of PPARgamma target gene was determined by reverse transcription-polymerase chain reaction (RT-PCR). ox-LDL evaluated PPARgamma phosphorylation status and subsequently decreased PPAR gamma target gene expression in a dose-dependent manner. ox-LDL also induced MAPK activation. Treatment of THP-1 cells with c-Jun N-terminal kinase-, but not p38- or extracellular signal-regulated kinase-MAPK inhibitor, significantly suppressed PPARgamma phosphorylation induced by ox-LDL, which in turn inhibited foam cell formation. In addition to its ligand-dependent activation, ox-LDL modulates PPAR gamma activity through phosphorylation, which is mediated by MAPK activation. PPARgamma phosphorylation mediated by MAPK facilitates foam cell formation from macrophages exposed to ox-LDL.Acta Pharmacologica Sinica 10/2006; 27(9):1146-52. · 1.95 Impact Factor -
Article: PPARγ phosphorylation mediated by JNK MAPK: a potential role in mac‐rophage‐derived foam cell formation1
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ABSTRACT: Aim: To investigate whether oxidized low-density lipoprotein (ox-LDL) modulates peroxisome proliferator-activated receptor γ (PPARγ) activity through phosphorylation in macrophages, and the effect of PPARγ phosphorylation on macrophages-derived foam cell formation. Methods: After exposing the cultured THP-1 cells to ox-LDL in the presence or absence of different mitogen-activated protein kinase (MAPK) inhibitors, PPARγ and phosphorylated PPARγ protein levels were detected by Western blot. MAPK activity was analyzed using MAP Kinase Assay Kit. Intracellular cholesterol accumulation was assessed by Oil red O staining and cholesterol oxidase enzymatic method. The mRNA level of PPARγ target gene was determined by reverse transcription-polymerase chain reaction (RT-PCR). Results: ox-LDL evaluated PPARγ phosphorylation status and subsequently decreased PPARγ target gene expression in a dose-dependent manner. ox-LDL also induced MAPK activation. Treatment of THP-1 cells with c-Jun N-terminal kinase-, but not p38- or extracellular signal-regulated kinase-MAPK inhibitor, significantly suppressed PPARγ phosphorylation induced by ox-LDL, which in turn inhibited foam cell formation. Conclusion: In addition to its ligand-dependent activation, ox-LDL modulates PPARγ activity through phosphorylation, which is mediated by MAPK activation. PPARγ phosphorylation mediated by MAPK facilitates foam cell formation from macrophages exposed to ox-LDL.Acta Pharmacologica Sinica 09/2006; 27(9):1146 - 1152. · 1.95 Impact Factor
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Institutions
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2008–2013
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Sun Yat-Sen University
- Department of Cardiology
Guangzhou, Guangdong Sheng, China
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2004
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Zhongshan University
Guangzhou, Guangdong Sheng, China
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