[Show abstract][Hide abstract] ABSTRACT: The present study used an in vitro model of cold cardioplegia in isolated working rat hearts to evaluate the possible role of ethyl pyruvate (EP) in promoting cardiac function and preventing apoptosis. Two groups of rats were evaluated; the EP (2 mM EP; n=8) and control (n=8) groups. Isolated rat hearts were perfused with Krebs-Henseleit buffer (KHB) for 30 min, arrested with cardioplegic solution and stored for 4 h in B21 solution at 4°C. The hearts were reperfused with KHB for 45 min. EP was added to the cardioplegic and storage solutions and also to KHB for reperfusion. Cardiac parameters of the heart rate, including left ventricular systolic pressure, left ventricular end-diastolic pressure, left ventricular developed pressure and maximal rise rate of the left ventricular pressure, were monitored. In addition, coronary flow, adenosine triphosphate (ATP) levels and malondialdehyde (MDA) content were recorded and apoptotic cell determination was detected. The functional parameters in the EP group were significantly higher compared with those in the control group during the reperfusion period (P<0.05). In addition, ATP levels were higher in the EP group than in the control group and the content of MDA was lower in the EP group than in the control group. A concentration of 2 mM EP significantly reduced the number of apoptotic cells in the EP group compared with that of the control group (P<0.05). Therefore, EP significantly preserved cardiac function, enhanced tissue ATP levels, attenuated myocardial oxidative injury and markedly reduced apoptosis following myocardial ischemia in an in vitro model of 4 h of cold cardioplegia and reperfusion.
Experimental and therapeutic medicine 05/2014; 7(5):1197-1202. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify the suitability of a conducting polymer-polypyrrole for development of a surface modification strategy of titanium, we electrocoated the monomer of pyrrole on titanium surface and produced an adherent polypyrrole coating. Then, this coating was characterised in terms of its mechanical and physical properties and also evaluated for in vivo and in vitro blood compatibility. It was found polypyrrole is more compatible than the bare titanium material with blood and possesses superior adhesion strength to titanium substrate and may serve as an ideal platform for anticoagulant functionalisation of titanium surface in the future.
International Journal of Biomedical Engineering and Technology 01/2012; 8(4).
[Show abstract][Hide abstract] ABSTRACT: Maraviroc (MVC), a specific antagonist of CCR5 expressed on macrophages and activated T cells, may modulate inflammation and may be useful in patients with HIV infection. In this study we used nonhuman primates to examine the effect and mechanism of MVC alone or in combination with cyclosporine (CsA) to prolong cardiac allograft survivals. In an established rhesus monkey cardiac allograft model, recipients treated with MVC plus CsA showed significantly prolonged survival of heart allografts (>240 d, p < 0.001). These in vivo results in the MVC/CsA group correlated with delayed alloantibody response and markedly decreased graft infiltration by CCR5(+), CD4(+), CD8(+), and CD68(+) cells (p < 0.05), as compared with other groups. Furthermore, grafts from the MVC/CsA group had elevated numbers of alternatively activated macrophages (AAMs) and the expression of peroxisome proliferator-activated receptor γ (PPARγ). Blockade of PPARγ abrogated the prolonged allograft survival (median survival time, 45 d) and the upregulated AAMs in MVC/CsA-treated recipients. In conclusion, MVC/CsA protects cardiac allograft in primates and this effect is associated with generating AAMs through activation of the PPARγ nuclear receptor.
The Journal of Immunology 02/2011; 186(6):3753-61. · 5.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interleukin (IL)-12 and -23 share the p40 subunit and are crucial for the development of T helper (Th) 1- and Th17-cell responses in acute graft rejection. However, little is known about the impact of treatment with antagonistic anti-p40 antibody in inhibiting rejection of cardiac allografts.
C57BL/6 mice were transplanted with syngeneic or allogeneic (BALB/c) hearts and treated with 100 or 200 μg or 400 μg anti-P40 monoclonal antibody on postoperative days 1 and 3, respectively. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility (endpoint). The severity of acute rejection was evaluated by histology and immunohistochemistry. The expression of transcription factors within the grafts were measured by quantitative real-time polymerase chain reaction. Systemically, the lymphocytes were characterized by flow cytometry, and the serum levels of cytokines were determined by ELISA.
In comparison with mice treated with isotype IgG or saline, treatment with anti-p40 significantly alleviated acute phase allograft rejection and resulted in prolonged survival of cardiac allografts (P<0.05). These changes were associated with reduced infiltration of inflammatory cells and down-regulation of Th1- and Th17-specific transcription factors and cytokines. Furthermore, treatment with anti-p40 significantly reduced the percentages of splenic Th1 and Th17 cells, but not Th2 and regulatory T cells (P<0.05), with concomitant reduction of serum interferon-γ and IL-17 levels (P<0.05).
Our data indicated that treatment with anti-p40 inhibited Th1- and Th17-cell responses and prolonged the survival of cardiac allografts in mice.
[Show abstract][Hide abstract] ABSTRACT: Form 2008 to 2009, four patients with complex thoracic aortic disease, including aortic aneurysms and dissections, were successfully treated in our department with a new treatment approach: hybrid procedure. Combined open surgery and endovascular repair were performed in these patients without deep hypothermia or circulatory arrest. Compared to those who underwent traditional open surgery in the same period, time of mechanical ventilation and ICU stay was decreased in these four patients. All of them were discharged soon after operation without postoperative complications or death. The result suggests that this new approach could be an option for thoracic aortic disease, but long-term and large-population studies are still required to demonstrate the safety and validity.
Journal of Huazhong University of Science and Technology 10/2010; 30(5):666-8. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study summarizes the clinical experience of surgical treatments of various types of thoracic aneurysm and aortic dissection. Clinical data of 122 patients with thoracic aneurysm and aortic dissection during July 2005 to July 2008 were retrospectively analyzed. The elective operations were performed in 107 patients while emergency surgery was done in 15 cases. Different surgical strategies were employed on the basis of diseased region, including simple ascending aortic replacement (n=3), aortic root replacement (n=43), hemi-arch replacement /total arch replacement+elephant trunk technique (n=32), thoracic/thoracoabdominal aortic replacement (n=8) and endovascular repair (n=36). In this series, there is 4 cases of perioperative death due to massive cerebral hemorrhage (n=1), respiratory failure (n=1) and multiple organ dysfunction syndrome (MODS) (n=2). Three cases developed post-operative massive cerebral infarction and the relatives of the patients abandoned treatment. Instant success rate of endovascular repair was 100%. The intimal rupture was sealed. Blood flow was unobstructed in true lumen and no false lumen was visualized. It was concluded that aggressive surgery should be considered in the patients with thoracic aneurysm and aortic dissection. Surgical procedures should vary with the location and the nature of the lesions.
Journal of Huazhong University of Science and Technology 05/2009; 29(2):207-11. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is an effective antiviral therapy in patients with HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this study we examined the inhibition of CCR5 in combination with the treatment with cyclosporine A in acute and chronic rejection in cardiac transplantation.
Eighty fully MHC-mismatched murine cardiac allograft models were randomized to four groups. Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B were given anti-CCR5 mAb alone, animals in group C were administered only CsA, and group D were the control group with PBS. Acute and chronic rejection was investigated on day 7 and day 45 post-transplant, respectively.
Allografts treated with anti-CCR5 mAb plus CsA showed significantly prolonged survival (44.73 +/- 0.258 d, P < 0.01) compared with PBS-treated group (11.067 +/- 0.707 d). Treatment with anti-CCR5 mAb plus CsA significantly inhibited the progression of CAV.
Our findings demonstrated that anti-CCR5 mAb in combination with CsA can prolong the survival of allograft and alleviate both acute and chronic allograft rejection. Thus, combined administration of anti-CCR5 mAb and CsA may become a new therapeutic approach for the prevention of cardiac graft failure that has not been obviated by conventional immunosuppressive agents.
Journal of Surgical Research 03/2009; 157(1):81-90. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The regulation of hypoxic response elements on the expression of vascular endothelial growth factor (VEGF) gene transfected to primary cultured rat skeletal myoblasts under hypoxic environment was investigated. pEGFP-C3-9HRE-CMV-VEGF vector was constructed with molecular biology technique and transfected to primary cultured rat skeletal myoblasts by lipofectamine in vitro. Gene expression of transfected myoblasts was detected by RT-PCR, Western blot and fluorescence microscope under different oxygen concentrations and different hypoxia time. The results showed that in hypoxia group, the VEGF gene bands were seen and with the decrease of oxygen concentrations and prolongation of hypoxia time, the expression of VEGF mRNA was obviously increased. Under hypoxic environment, the expression of VEGF protein in the transfected myoblasts was significantly increased. EGFP was expressed only under hypoxic environment but not under normoxic environment. It was concluded that hypoxia promoter could be constructed with HRE and regulate the expression of VEGF gene under hypoxic and normoxic environment, which could enhance the reliability of gene therapy.
Journal of Huazhong University of Science and Technology 11/2008; 28(5):568-71. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The chemokine receptor CCR5 plays important roles in acute allograft rejection. In this study, we examined the inhibition of CCR5 in combination with the treatment with cyclosporine A (CsA) in chronic rejection in cardiac transplantation. Forty-five transplant recipients were randomized to three groups. Recipients in group A were treated with anti-CCR5 mAb and CsA, mice in group B were given anti-CCR5 mAb alone, and animals in group C were administered with only CsA. On day 45 after transplantation, the allografts were harvested and examined by immunohistologic technique and PT-PCR methods. Allografts treated with anti-CCR5 mAb and CsA showed significantly prolonged survival (44.73 ± 0.258 days, P < 0.01) as compared with CsA-treated group (37.00 ± 2.04 days). Treatment with anti-CCR5 mAb plus CsA significantly inhibited the progression of cardiac allograft vasculopathy. Our findings demonstrated that anti-CCR5 mAb in combination with CsA can prolong the survival of allograft through their cardio-protective and immunomodulative properties. Thus, combined administration of anti-CCR5 mAb and CsA may become a new therapeutic approach for the prevention of cardiac graft failure that has not been obviated by conventional immunosuppressive agents.
Transplant International 10/2008; · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.
Journal of Huazhong University of Science and Technology 06/2008; 28(3):281-3. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.
Journal of Huazhong University of Science and Technology 04/2008; 28(2):147-51. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To reduce restenosis in vein grafts after coronary artery bypass grafting, to investigate the effect of human tissue factor pathway inhibitor (TFPI) gene delivery on neointima formation.
The eukaryotic expressed plasmid vector pCMV-(Kozak) TFPI was constructed. Forty-eight Japanese white rabbits were randomly divided into 3 groups with 16 rabbits in each group: TFPI group, empty plasmid control group and empty control group. Animal model of common carotid artery bypass grafting was constructed. Before anastomosis, vein endotheliocytes were transfected with cationic liposome containing the plasmid pCMV-(Kozak) TFPI (400 microg) by pressurizing infusion (30 min) in TFPI group. In empty plasmid control group, vector pCMV-(Kozak) TFPI was replaced by empty plasmid pCMV (400 microg). In empty control group, those endotheliocytes were not interfered. After operation, vein grafts were harvested at 3 days for immunohistochemical, RT-PCR and Western-blot analyses of exogenous gene expression and at 30 days for histopathology measurement of intimal areas, media areas and calculation of intimal/media areas ratio. Luminal diameter and vessel wall thickness were also measured by vessel Doppler ultrasonography and cellular category of neointima was analyzed by transmission electron microscope at 30 days after operation.
Human TFPI mRNA and protein were detected in TFPI group. The mean luminal diameter of the TFPI group, empty plasmid control group and empty control group was (2.68 +/- 0.32) mm, (2.41 +/- 0.23) mm and (2.38 +/- 0.21) mm respectively. There were statistically significant differences between TFPI group and control groups (P < 0.05). The vessel wall thickness of the TFPI group, empty plasmid control group and empty control group was (1.09 +/- 0.11) mm, (1.28 +/- 0.16) mm and (1.34 +/- 0.14) mm respectively. There were statistically significant differences between TFPI group and other control groups (P < 0.01). The mean intimal areas, the ratio of the intimal/media areas of the TFPI group were (0.62 +/- 0.05) mm2 and 0.51 +/- 0.08 respectively,whichwere reduced compared withthose of the two control groups (P < 0.05). The mean media areas had no significant differences among three groups (P > 0.05). Through transmission electron microscope analyses,no smooth muscle cells were seen in neointima of TFPI group in many visual fields,but smooth muscle cells were found in neointima of two control groups.
Human TFPI gene transfection reduced intimal thickness in vein grafts.
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 03/2008; 22(3):354-8.
[Show abstract][Hide abstract] ABSTRACT: We have established a human umbilical vein endothelial cell (HUVEC) line monoclonal cells with the stable expression of human tissue-type plasminogen activator (t-PA) gene to provide a basis for further study on the vascular tissue engineering. Recombinant plasmid pcDNA3. 1-Myc-His B (-)/t-PA was constructed by insertion of t-PAcDNA originated from PBS/t-PA into eukaryotic expression vector pcDNA3. 1-Myc-His B(-) and transfected into hUVEC line cells mediated by lipofectamine. The positive clones were obtained by the screen of G418. The transcription and expression of t-PA gene were investigated by RT-PCR and Western blotting respectively. The t-PA activity was measured by chromogenic substrate assay. The positive clone cells which transcripted the mRNA of t-PA gene was obtained by RT-PCR. Immunoreactive human t-PA of the medium was significantly increased in the group of transfected gene when compared with that in the controlled and transfected plasmid without t-PA gene group. The biological activity of the protein of the t-PA in the media was increased significantly in the positive clone cells with t-PA gene transfected. The HUVEC line monoclonal cells with the stable expression of t-PA gene was established successfully.
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 01/2008; 24(6):1330-3.
[Show abstract][Hide abstract] ABSTRACT: To investigate whether peroxisome proliferators-activated receptor-gamma (PPARgamma) ligand Troglitazone can reduce endothelial injury and activation during storage of harvested saphenous vein grafts. Segments of human saphenous vein graft were collected from 9 patients undergoing coronary bypass surgery and then divided into two equal parts of control and test specimens, were stored in either heparinized blood (control group) or heparinized blood containing 20 mumol/L troglitazone (test group) for 1 h at room temperature. Tissue distribution and protein expression of VCAM-1, ICAM-1, and endothelial nitric oxide synthase (eNOS) were compared using immunohistochemistry and Western blot analysis. Myeloperoxidase (MPO) activity, a marker of neutrophil sequestration in human saphenous vein grafts, was also measured in each group. The expression of ICAM-1 (753+/-132 versus 7201+/-934; P<0.01), VCAM-1 (3731+/-294 versus 8292+/-793; P<0.01), and MPO activity (1.52+/-0.42 U/g, 5.04+/-1.26 U/g P<0.01) were significantly lower in test group. In contract, eNOS expression (7983+/-834 versus 3989+/-1008; P<0.01) was significantly higher in test group. PPARgamma ligand troglitazone might reduce endothelial injury during the storage period of human saphenous vein grafts.
Journal of Huazhong University of Science and Technology 01/2008; 27(6):657-9. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of oxidized low density lipoprotein (ox-LDL) on the proliferation of cultured human vascular smooth muscle cells (vSMC) were investigated in vitro. By using NaBr density gradient centrifugation, LDL was isolated and purified from human plasma. Ox-LDL was produced from LDL by being incubated with CuSO(4). ox-LDL was then added to the culture medium at different concentrations (35, 60, 85, 110, 135 and 160 microg/mL) for 7 days. The influence of ox-LDL on vSMC proliferation was observed in growth curve, mitosis index, and in situ determination of apoptosis. The data were analyzed with SPSS 10.0 software. The results showed that the ox-LDL produced in vitro had a good purity and optimal oxidative degree, which was similar to the intrinsic ox-LDL in atherosclerotic plaque. ox-LDL at a concentration of 35 microg/mL demonstrated the strongest proliferation inducement, and at a concentration of 135 microg/mL, ox-LDL could inhibit the growth of vSMC. ox-LDL at concentrations of 35 and 50 microg/mL presented powerful mitotic trigger, and with the increase of ox-LDL concentration, the mitotic index of vSMC was decreased gradually. ox-LDL at higher concentrations promoted more apoptotic vSMCs. ox-LDL at lower concentrations triggered proliferation of vSMCs, and at higher concentrations induced apoptosis in vSMCs. ox-LDL played a promotional role in the pathogenesis and development of atherosclerosis by affecting vSMC proliferation and apoptosis.
Journal of Huazhong University of Science and Technology 03/2007; 27(1):20-3. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to study the cardioprotective effects of diazoxide on the myocardial ischemia/reperfusion injury of rats and mechanisms, the healthy SD rats were randomly divided into 2 groups: the rats in the experimental group were injected with diazoxide for preconditioning with the dosage of 12.5 mg/kg through the right femoral vein and those in the control group was only administered with the equal volume of media. After 10 min, a left thoracotomy was performed and the left anterior descending branch was occluded for 2 h. Two h later, the left anterior descending branch was reperfused for 2 h and then the heart was quickly excised to be used for measurement of MDA, SOD and the infarct size, in situ cell apoptosis detection and observation of the cell ultrastructure by electron microscopy. The results showed that as compared with the control group. MDA, the infarct size and cell apoptosis in the experimental group were greatly reduced (P<0.05). And the cell ultrastructure was obviously improved. But the activity of SOD had no change (P>0.05). It was concluded that diazoxide could protect the rats from myocardial ischemia/reperfusion injury, which might be contributed to the reduction of lipid peroxidation and cell apoptosis.
Journal of Huazhong University of Science and Technology 12/2006; 26(6):690-2. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data from 736 patients undergoing prosthetic heart valve replacement surgery and concomitant surgery (combined surgery) from January 1998 to January 2004 at Union Hospital were retrospectively reviewed. Univariate logistic regression analyses were conducted to identify risk factors For prolonged mechanical ventilation. The results showed that prolonged cardiopulmonary bypass duration, prolonged aortic cross clamp time and low ejection fraction less than 50 percent (50%) were found to be independent predictors for prolonged mechanical ventilation. Meanwhile age, weight, and preoperative hospital stay (days) were not found to be associated with prolonged mechanical ventilation. It was concluded that, for age and weight, this might be due to the lower number of old age patients (70 years and above) included in our study and genetic body structure of majority Chinese population that favor them to be in normal weight, respectively.
Journal of Huazhong University of Science and Technology 02/2006; 26(6):693-5. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of in vivo local expression of recombined human tissue-type plasminogen activator (t-PA) gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting was performed on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according to the different processing methods: transfected t-PA gene group (n = 24), vector group (n = 24) and blank control group (n = 24). Samples of vein grafts were harvested at different time points after surgery. The expression of t-PA gene in vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western-Blot assay. The t-PA activity was measured by chromogenic substrate assay. The Cr51 labeled platelets accumulation in vein grafts was counted. The histopathological changes were compared in intima hyperplasia index among the three groups after operation. The results showed that at the 2nd, 5th, 14th and 28th day after operation, RT-PCR and Western-blot confirmed the expression of t-PA mRNA and protein at the site of gene transfer. The t-PA activity detected on the 2nd, 5th, 14th and 28th day in experimental group was 370.63 +/- 59.44, 344.13 +/- 48.47, 252.87 +/- 51.80 and 161.75 +/- 68.94 U/g respectively, and disappeared on the 60th day and undetected in the control groups. The number of platelets accumulated in the vein grafts in gene group, vector group and blank control group was (85.04 +/- 21.58) 10(6), (225.87 +/- 85.13) 10(6) and (211.7 +/- 78.02) 10(6) respectively. The number of platelets accumulated in gene group was significantly fewer than that in the control groups. Morphometric analysis revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as compared with that in the control groups. It was suggested that the local expression of t-PA gene in vein graft significantly inhibited the accumulation of platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of bypass graft could be prevented effectively.
Journal of Huazhong University of Science and Technology 02/2006; 26(3):314-6. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of cyclosporine A (CsA) on Angiontensin II (Ang II)-induced protein contents, c-fos protein levels and cytosolic Ca2+ level ([Ca2+]i) in cultured cardiomyocytes of neonatal rats were observed. Total protein contents were determined by Bradford method. The expression of c-fos protein was detected by Western blot. [Ca2+]i labeled with fluorescent probe Fluo-3/AM was measured under a laser scanning confocal microscope. The results revealed that as compared with control, the total protein contents were increased in cardiomyocytes treated with Ang II (10(-7) mol/ L), which could be inhibited by CsA in a dose-dependent manner. It was found that Ang II could increase the c-fos protein expression, which could be inhibited by CsA in a dose-dependent manner. Ang II induced the [Ca2+]i elevation in cardiomyocytes. CsA did not influence the resting intracellular Ca2+, but inhibited significantly the Ang II-induced [Ca2+]i elevation. It was concluded that CsA can suppress the Ang II-induced c-fos protein expression and [Ca2+]i elevation in single cardiomyocyte, which might play a role in the prevention of Ang II-induced cardiomyocyte hypertrophy by CsA.
Journal of Huazhong University of Science and Technology 02/2005; 25(5):558-60. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic acid (3-NPA, 4 mg/kg) and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30-min ischemia and 60-min reperfusion. The HR, LVDP and +/- dp/dt(max) were measured at pre-ischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and +/- dp/dt(max) recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group. It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.
Journal of Huazhong University of Science and Technology 02/2005; 25(4):439-41. · 0.78 Impact Factor