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FINITE ELEMENT ANALYSIS OF cardiac myocyte DEBONDING AND REORIENTATION DURING CYCLIC SUBSTRATE STRETCH EXPERIMENTS

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Acta Mechanica Solida Sinica 2009年第4期22卷 307-319页

作者： Tao Tang Jun Qiu Meng Zhang Zhuo Zhuang School of Aerospace Tsinghua University Beijing 10084 China

The substrate stretch experiment, which is carried out on several kinds of adherent cells, is usually used to catch the physiological variation and morphological response to cyclic substrate deformation. In this paper, stretch loading was exerted on cardiac myocytes cultured on silica substrates using a custom-made substrate stretch device. The effect of stretch on the alignment orientation of cardiac myocytes was studied through morphocytological statistics. Under cyclic stretch stimulus, the long axes of cardiac myocytes oriented perpendicularly to the stretch direction for continuous stretch acting. However, the mechanism underlying these behaviors is not well understood from such in vitro tests. Finite element （FE） model was developed in the analysis to investigate these behaviors. Xu-Needleman formulation was used to define the interaction behavior for contact surfaces between cell and substrate. The role of cell viscoelasticity nature is studied in adherent cell debonding with the substrate and aligning perpendicular to the stretch direction during long time cyclic stretch stimulation. There were four different strain magnitudes considered in the simulation to find out the cell debonding affected by the cyclic strains. The potential role of cyclic strain frequency in regulating cell debonding and alignment was also studied using FE analysis.

关键词： cardiac myocyte cyclic substrate stretch cell adhesion finite element

Antioxidant Effect of Human Selenium-containing Single-chain Fv in Rat cardiac myocytes

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Chemical Research in Chinese Universities 2009年第2期25卷 216-219页

作者： HUO Rui SHI Yi XU Jun-jie YAN Fei LV Shao-wu SU Jia-ming DUAN Yu-jing FAN Jia NING Bo CONG Deng-li YAN Gang-lin LUO Gui-min WEI Jing-yan College of Pharmaceutical Science Changchun 130021 P. R. China Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education Changchun 130021 P. R. China College of Life Science Jilin University Changchun 130021 P. R. China

Reactive oxygen species（ROS） plays a key role in human heart diseases. Glutathione peroxidase（GPX） functions as an antioxidant as it catalyzes the reduction of hydroperoxide. In order to investigate the antioxidant effect of human selenium-containing single-chain Fv（Se-scFv-B3）, a new mimic of GPX, a model system of hydrogen peroxide（H202）-induced rat cardiac myocyte damage was established. The cardiac myocyte damage was characte- rized in terms of cell viability, lipid peroxidation, cell membrane integrity, and intracellular H202 level. The Se-scFv-B3 significantly reduced H2O2-induced cell damage as shown by the increase of cell viability, the decline of malondialdehyde（MDA） production, lactate dehydrogenase（LDH） release, and intracellular H2O2 level. So Se-scFv-B3 may have a great potential in the treatment of human heart diseases induced by ROS.

关键词： Human single-chain Fv Selenium Glutathione peroxidase H202 cardiac myocyte

Effects of simvastatin on hypertrophy and PTEN expression of rat cardiac myocytes

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Journal of Geriatric Cardiology 2010年第1期7卷 47-51页

作者： Yong-Qing Chen Lian-You Zhao Wei-Ze Zhang Ming-Xu Zhang Ling Ma Department of Cardiology Lanzhou General Hospital Lanzhou Military Command Lanzhou 730050 China Department of Cardiology Tangdu Hospital Fourth Military Medical University Xi＇an 710038 China

Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role ofphosphatase and tensin homolog deleted on chromosome ten （PTEN） in the signal pathway. Methods Cultured neonatal Sprague- Dawley （SD） rat cardiac myocytes were treated with 15% fetal bovine serum, or without serum, or different consentrations of simvastatin. Image analysis system was used to measure the cardiac myocytes surface area. Protein synthesis of myocytes was measured via [3H]-leucine incorporation method. The expression level of atrial natriuretic peptide （ANP） mRNA in myocytes was determined with reverse transcription polymerase chain reaction （RT-PCR）. The mRNA and protein expression levels of PTEN in cardiac myocytes were investigated with RT-PCR and Western blot respectively. Results At 24 hours, cardiac myocytes surface area was significantly higher in 15% serum group （1611.16± 160.75 lam2） than in serum-free group （538.04±118.60 ±tm2, P〈0.01）. Simvastatin decreased the cell surface area in a concentration dependent manner. The cell surface area in 10-5 and 10-6 mol/L simvastatin groups were 799.84＋ 167.70 ±tm2 and 1076.88± 199.28 um2 respectively, which were both significantly lower than that in 15% fetal bovine serum group （P〈0.01）. Incorporation rate of [3H]-leucine was significantly higher in 15% fetal bovine serum group （2360± 106cpm/well） than that in serum-free group （1305±92 cpm/well, P〈0.01）. Incorporation rate of [3H]-leucine in 10.5 and 10.6 mol/L simvastatin groups were 1707±101 clam/well and 1962±125 cpm/well respectively, which were both lower than that in serum group （P〈0.01）. With the increase of simvastatin concentration, the expression level ofANP mRNA in cardiac myocytes was decreased gradually, which were 0.29±0.03 and 0.40-±0.03 respectively in 10.5 and 10-6 mol/L simvastatin groups, and significantly lower than that in serum group（0.60-±.03, P〈0.01）. Simvastatin increased the expressions of PTEN mRNA an

关键词： simvastatin cardiac myocyte hypertrophy PTEN

Role of NF-κB in protection of EPO pretreatment on neonatal rat cardiac myocytes with hypoxia/reoxygenation injury

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Journal of Medical Colleges of PLA(China) 2005年第4期20卷 223-227页

作者：秦川肖颖彬钟前进陈林王学锋 Department of Cardiovascular Surgery Xinqiao Hospital Third Military Medical University Chongqing 400037 China

Objective：To observe the protective effects of erythropoietin （EPO） pretreatment on cardiac myocyte with hypoxia/reoxygenation （H/R） injury and the role of NF-κBin this effects. Methods：After the H/R model of cardiac myocytes of neonatal rats was established, the cultured cardiac myocytes were divided into 4 groups, including EPO pretreatment group （ EPO 10 U/ml 24 h before H/R）, EPO pretreatment ＋ PDTC group（EPO 10 U/ml and PDTC 5 μg/ml 24 h before H/R）, PDTC group （PDTC 5 μg /ml 24 h before H/R） and eomrolgroup. Before and after the H/R, assay of LDH concentration in the culture medium, the survival rate of the myocytes tested by MTT chromatometry and the apoptosis by flow cytometry were undertaken. Activation of NF-κB was determined by EMSA before and after H/R. Results：EPO pretreatment markedly reduced the LDH concentration in the medium, elevated the survival rate of myocytes and inhibited the apoptosis after H/R. Addition of PDTC during the pretreatment abol- ished the protective effects of EPO pretreatment. NF-κB was markedly activated during EPO pretreatment and PDTCinhibited the activation. However, after H/R, the activity of NF-κB in myocytes with EPO pretreatment was significantly inhibited compared to the other myocytes. Conclusion：NF-κB is significantly activated during EPO pretreatment, but is inhibited after H/R, which is correlated with the protective effects of EPO pretreatment on cardiac myocytes with H/R. This phenomenon can be explained as the negative feedback mechanism of the activation of NF-κB.

关键词： erythropoietin cardiac myocyte hypoxia/reoxygenation NF-κB

GRK5 is an essential co-repressor of the cardiac mineralocorticoid receptor and is selectively induced by finerenone

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World Journal of Cardiology 2022年第4期14卷 220-230页

作者： Celina M Pollard Malka S Suster Natalie Cora Alexandra M Carbone Anastasios Lymperopoulos Laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences(Pharmacology)College of PharmacyNova Southeastern UniversityFort LauderdaleFL 33328-2018United States

BACKGROUND In the heart,aldosterone(Aldo)binds the mineralocorticoid receptor(MR)to exert damaging,adverse remodeling-promoting *** recently showed that G protein-coupled receptor-kinase(GRK)-5 blocks the cardiac MR by directly phosphorylating it,thereby repressing its transcriptional *** antagonist(MRA)drugs block the cardiac MR reducing morbidity and mortality of advanced human heart ***-steroidal MRAs,such as finerenone,may provide better cardio-protection against Aldo than classic,steroidal MRAs,like spironolactone and *** To investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent *** We used H9c2 cardiomyocytes,which endogenously express the MR and *** GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to *** eplerenone,finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity,thus displaying inverse ***5 is necessary for finerenone’s inverse agonism,since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional *** alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression ***,GRK5 is necessary for the antiapoptotic,anti-oxidative,and anti-fibrotic effects of both finerenone and eplerenone against Aldo,as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis,oxidative stress,and *** Finerenone,but not eplerenone,induces GRK5-dependent cardiac MR inhibition,which underlies,at least in part,its higher potency and efficacy,compared to eplerenone,as an MRA in the ***5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

关键词： Aldosterone cardiac myocyte Finerenone G protein-coupled receptor kinase-5 Mineralocorticoid receptor antagonist Signal transduction

Antioxidant Effect of Selenium-containing Glutathione S-Transferase in Rat Cardiomyocytes

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Chemical Research in Chinese Universities 2012年第3期28卷 454-458页

作者： YIN Li HAN Xiao YU Yang GUO Xiao REN Li-qun FANG Jing-qi LIU Zhi-yi YAN Gang-lin WEI Jing-yan College of Pharmaceutical Science Jilin UniversityChangchun 130021P.R.China Key Laboratory of Molecular Enzymology and Engineering Ministry of EducationCollege of Life ScienceJilin UniversityChangchun 130012P.R.China

As one of the most important antioxidant enzymes, glutathione peroxidase（GPX） protects cells and tissues from oxidative damage, and plays an important role in cardiovascular and cerebrovascular injuries induced by oxida- tive stress. The antioxidant effect of selenium-containing glutathione S-transferase（Se-GST）, a mimic of GPX was investigated on rat cardiomyocytes. To explore the protection function of Se-GST in hydrogen peroxide（H202） chal- lenged rat cardiomyocytes, we examined malondialdehyde（MDA）, lactate dehydrogenase（LDH）, superoxide dismu- tase（SOD） and cell apoptosis. The results demonstrate exposure of rat cardiomyocytes to H202 for 6 and 12 h induced the significant increases of MDA, LDH and apoptosis rate of cardiomyocytes, but pretreatment of rat cardiomyocytes with Se-GST at 0.0005 or 0.001 unit/mL prevents oxidative stress induced by H202 with the decreases of cell apopto- sis. All the results hint Se-GST has antioxidant activity for oxidative stress challenged rat cardiomyocvtes.

关键词： Selenium-containing glutathione S-transferase(Se-GST) Cell apoptosis cardiac myocyte Oxidative stress

The Study on Intramyocardial Calcium Overload and Apoptosis Induced by Cosackievirus B3

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第3期21卷 256-258,262页

作者：胡秀芬王宏伟鲁维伟董永绥程佩萱 Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan

The isolated cardiac myocytes of rats were immediately infected by cosackievirus B3 (CVB3) to investigate the effects of such procedure on the cell cycle, apoptosis and intracellular ionized calcium (Ca 2+ i) of cardiac myocytes. Newborn Balb/c murine cardiac myocytes were cultivated, then infected by CVB3. Intracellular Ca 2+ i was measured by flow cytometer. The calcium in the medium for culturing cardiac myocytes was detected by using atom absorb spectrum test. It was found that CVB3 could markedly inhibit the differentiation and proliferation of the infected cardiac myocytes and induce the apoptosis. The intracellular Ca 2+ i level in the infected group was significantly higher than in the control group (Pcardiac myocytes in the infected group was significantly lower than in the control group (Pcardiac myocytes are likely to play an important role in the pathogenesis of viral myocarditis.

关键词： cosackievirus B3 cardiac myocyte apoptosis intracellular ionized calcium

Heat shock protein 70 gene transfection protects rat myocardium cell against anoxia-reoxygeneration injury

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Chinese Medical Journal 2007年第7期120卷 578-583页

作者： LIU Ji-chun HE Ming WAN Li CHENG Xiao-shu Department of Cardiovascular Surgery First Affiliated Hospital of Nanchang University Nanchang 330006 China Department of Pharmacology Medical College of Nanchang University Nanchang 330006 China Department of Cardiovascular Medicine Second Affiliated Hospital of Nanchang University Nanchang 330006 China

Background A number of studies suggest that the expression of heat shock protein 70 （HSP70） induced by heat stress are associated with protection against ischemia-reperfusion injury. But the protective effects may be contaminated by other factors in the same stress. This study was conducted to explore the protective role of HSP70 expression in acute myocardial anoxia/reoxygeneration （A/R） injury with a liposome-mediated gene transfer technique for the introduction of pCDNA HSP70 into the neonatal rat myocardial cells. In addition, heat shock stress cytoprotection was also investigated for comparison. Methods The cultured primary neonatal rat myocardiocytes with an acute myocardial A/R injury model and the HS-treated rat myocardiocyte model were used. Three-day cultured myocardiocytes were randomly divided into four groups （n=8）： control group, A/R group, HS＋A/R group and pCDNA HSP70 ＋A/R group. A liposome-coated HSP70 pCDNA plasmid was transfected into the primary neonatal rat myocardiocytes; HSP70 mRNA and its protein were confirmed by reverse transcriptase polymerase chain reaction （RT-PCR） and Western blotting. The cell viability was assayed by monotetrazolium （MTT） and the lactate dehydrogenase （LDH） and creatine phosphokinase （CPK） activity of cells during incubation and the changes in cells ultrastructure were examined. NF-κB activity in the primary neonatal rat myocardiocytes was measured with flow cytometry. Results Compared with viability in the A/R group （（35.4±6.9）%） the cell viability in the HS＋A/R group （（72.8±11.6）%） and the pCDNA HSP70 ＋ A/R group （（76.3±12.2）%） was improved significantly （P〈0.05）. The activity of LDH and CPK was significantly elevated in the A/R group. However, in the HS＋A/R group and pCDNA HSP70 ＋A/R group, significant decreases in activity were observed. The cell ultrastructure of the A/R group cells was abnormal, whereas nearly normal ultrastructure was observed in HS＋A/R group and pCDNA HSP70＋A/R group. HSP70 mRNA and protein

关键词： gene transfection HSP70 gene NF-κB cardiac myocyte anoxia-reoxygeneration injury

Concentration-and calcium-dependent effects of calmodulin and its mutants on L-type Ca2+channel in guinea pig ventricular myocytes

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Concentration-and calcium-dependent effects of calmodulin an...