Cheng-xing Shen

Southeast University (China), Nanjing, Jiangxi Sheng, China

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Publications (10)14.38 Total impact

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    ABSTRACT: BACKGROUND: The impairment of the tissue kallikrein (KLK1)-kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD). METHODS: KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls. Patients were followed-up for the incidence of major adverse cardiovascular events (MACE) for 8 months to 2 y. Gene expression of KLK1, CD105 and CD68 was assessed in human coronary endarterectomy specimens. RESULTS: Patients with CAD and acute coronary syndrome (ACS) had significantly elevated KLK1 levels. In addition, the concentration of hs-CRP was increased in ACS patients. A strong positive correlation between plasma KLK1 and the severity of CAD was also demonstrated, suggesting that high KLK1 levels are an independent predictor for CAD. MACE during follow-up significantly correlated with KLK1 levels in the ACS group. Unstable coronary plaques demonstrated markedly increased KLK1 levels, macrophage infiltration and high microvessel density. Additionally, KLK1 staining primarily colocalized with macrophages. CONCLUSIONS: In the present study, plasma KLK1 levels were a useful predictor for the presence and extent of CAD. More extensive studies are, however, necessary in order to validate these findings.
    Clinica chimica acta; international journal of clinical chemistry 04/2013; · 2.54 Impact Factor
  • Chinese medical journal 10/2012; 125(19):3581-3. · 0.90 Impact Factor
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    ABSTRACT: Superparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI). An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination. MR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination. We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.
    Chinese medical journal 04/2011; 124(8):1199-204. · 0.90 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells. In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.1-Lacz plasmid (Lacz-MSCs group), (3) MSCs transfected with pcDNA3.1-hHO-1 (HO-1-MSCs group), and (4) MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin (SnPP) (HO-1-MSCs + SnPP group). Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at < 1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor (TGF-β) and fibroblast growth factor (FGF-2) in the supernatant. In vivo, 28 Chinese mini-pigs were randomly allocated to the following treatment groups: (1) control group (saline), (2) Lacz-MSCs group, (3) HO-1-MSCs group, and (4) HO-1-MSCs + SnPP group. About 1 × 10(7) of autologous stem cells or an identical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging (MRI) assay and postmortem analysis were assessed four weeks after stem cell transplantation. Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs ((874.88 ± 68.23) pg/ml) compared with Lacz-MSCs ((687.81 ± 57.64) pg/ml, P < 0.001). FGF-2 was also significantly increased in the HO-1-MSCs ((1106.48 ± 107.06) pg/ml) compared with the Lacz-MSCs ((853.85 ± 74.44) pg/ml, P < 0.001). In vivo, at four weeks after transplantation, HO-1 gene transfer increased the capillary density in the peri-infarct area compared with the Lacz-MSCs group (14.24 ± 1.66/HPFs vs. 11.51 ± 1.34/HPFs, P < 0.001). Arteriolar density was also significantly higher in HO-1-MSCs group than in the Lacz-MSCs group (7.86 ± 2.00/HPFs vs. 6.45 ± 1.74/HPFs, P = 0.001). At the same time, the cardiac function was significantly improved in the HO-1-MSCs group compared with the Lacz-MSCs group ((53.17 ± 3.55)% vs. (48.82 ± 2.98)%, P < 0.05). However, all these effects were significantly abrogated by SnPP. MSCs provided a beneficial effect on cardiac function after ischemia/reperfusion by the induction of therapeutic angiogenesis, and this effect was amplified by HO-1 overexpression.
    Chinese medical journal 02/2011; 124(3):401-7. · 0.90 Impact Factor
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    ABSTRACT: To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion. Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.1-nHO-1 (HO-1-MSCs). 1 x 10(7) of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation. In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1-MSCs group (30.30% +/- 7.64%) compared with that in MSCs group (56.93% +/- 4.68%, P < 0.001) and LacZ-MSCs group (55.88% +/- 4.38%, P < 0.001), VEGF was also significantly upregulated in HO-1-MSCs group [(768.44 +/- 78.38) pg/ml] compared with that in MSCs group [(555.27 +/- 67.67) pg/ml, P < 0.001] and LacZ-MSCs group [(522.97 +/- 71.45) pg/ml, P < 0.001]. In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P < 0.05 vs.saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation (53.50% +/- 2.09% vs. 49.54% +/- 2.74%, P = 0.017), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [(14.59 +/- 2.39)/HPF vs. (11.78 +/- 2.48)/HPF, P = 0.033]. Efficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 08/2009; 37(8):692-5.
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    ABSTRACT: To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging. AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n = 6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI. Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/- 3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/- 1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05) compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs. 40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs. 41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR-MNC transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2) were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05), myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR-MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3 +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR-MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/- 0.2, P < 0.05). Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size, improved cardiac function. MR-MSC is superior to MR-MNC on improving cardiac function.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 11/2008; 36(11):1004-8.
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    ABSTRACT: Drug-eluting stents have been used to markedly decrease in-stent restenosis in 6 months, but they are noticed due to the late thrombogenicity. The purpose of the present study was to evaluate the biocompatibility of Tetramethylpyrazine-eluting stents by investigating the intimal response and thrombogenicity in normal porcine coronary arteries by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS) and histomorphometry. Bare metal stents (BMS) were uniformly spray-coated with Tetramethylpyrazine (TMP 200 microg) and prepared for TMP-eluting stents (TES). Fourteen coronary arteries in 14 pigs underwent stent implantation. Seven TES were implanted in 7 pigs and 7 BMS in other 7 pigs. The stents were deployed with a stent-to-artery ratio of 1.1-1.2/1.0 in order to induce vascular wall injury. QCA and IVUS were performed before and immediately after the implantations and at 28 days (end time point). The analysis on blood cell count, biochemical parameters, status of behavior of pigs were evaluated before the implantation and at the time of 1 and 28 days. Stented-coronary arteries, stented-coronary arteries related ventricular wall, lung, liver and kidney were harvested after euthanasia of animals at the endpoint. Histopathology and histomorphometry had been done to assess the local toxicity of TES to these organs. All the stents were successfully implanted, however, 4 pigs died of cardiac tamponade or anesthesia. No bone marrow depression and hemolysis was seen. No damage to the function and metabolism of liver and kidney was discovered. No thrombosis was found in control and test groups. Few inflammatory cells were found in the stented-coronary artery walls at each endpoint in both groups. No damage to stented-coronary arteries related ventricular wall, lung, liver and kidney was detected due to TES implantation. Compared with the control group, the neointimal area was significantly reduced in the TES group (60.2+/-23.5% vs 10.0+/-2.1%, P=0.01) by IVUS analysis, but the lumen area in the TES group was increased (4.34+/-0. 93 mm(2) vs 1.29+/-1.02 mm(2), P=0.011), the neointimal area was reduced markedly (1.51+/-0.45 mm(2) vs 4.60+/-1.39 mm(2), P=0.004). The biocompatibility of TES in porcine model at 28 days seems to be good and acceptable. Biocompatibility can be evaluated by IVUS and histopathology in a porcine restenosis model.
    Biomedecine [?] Pharmacotherapy 03/2008; 62(2):125-9. · 2.07 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging. Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01). A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group. Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.
    Chinese medical journal 03/2008; 121(6):544-50. · 0.90 Impact Factor
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    ABSTRACT: We aim to track mesenchymal stem cells (MSCs) after magnetically labeling and test the ability of these cells differentiate into cardiomyocytes in vivo. Therefore, 20 swines were divided into four groups, sham-operated group (n=3); acute myocardial infarction (AMI) transplanted with PBS (n=3); labeled MSCs (n=7) and unlabeled MSCs (n=7) group. 10(7) labeled or unlabeled cells were intracoronary delivered after MI (4.8+/-1.3 days), and serial cardiac MR (3.0T) imaging studies were performed at 0, 4 and 8 weeks after transplantation, then the results were confirmed by histological and western blot analysis. We demonstrated that labeled MSCs can be reliably detected and tracked in vivo using MR imaging. In particular, we provided the evidence of regeneration of labeled MSCs in vivo by histological examination and western blot analysis.
    International journal of cardiology 01/2008; 131(3):417-9. · 6.18 Impact Factor
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    ABSTRACT: To investigate the efficacy of magnetic resonance imaging (MRI) in tracking bone marrow derived mononuclear cells (BM-MNCs) labeled with superparamagnetic iron oxide (SPIO) nanoparticles. BM-MNCs were isolated from the bone marrow of 14 pigs. These 14 pigs underwent occlusion of the left anterior descending coronary artery (LAD) to establish myocardial infarction (MI) models and then randomly divided into 2 groups: experimental group (n = 9) to be injected with BM-MNCs labeled with SPIO intracoronarily under X-ray fluoroscopy, and control group (n = 5), to be injected with unlabelled BM-MNCs MRI was performed with a 1.5T MR scanner to demonstrate the location of the BM-MNCs once a week. T pigs were killed when no labeled BM-MSC was detected. The hearts were taken out to undergo HE staging and Prussian blue staining. Immunohistochemistry was used to detect the desmin and myosin. The cell labeling efficiency was almost 100%. Contrast-enhanced MRI demonstrated successful establishment of MI models. Effective MRI tracking findings were obtained in 8 pigs, 7 of the experimental group and 3 of the control group. In 3 pigs T2* weighted MRI showed the zone of labeled cell accumulation shows vague low-signal area around the infarction area and much better conspicuity of the zone of hypoenhancement was shown under contrast-enhanced MRI. The hypoenhancement zone disappeared 14 - 21 days after the injection of BM-MSCs. Histological analyses showed that most Prussian blue positive cells were well correlated with the area where a signal intensity loss was observed in MRI. 1.5T MR imaging can monitor the magnetically labeled BM-MNC in vivo in myocardial infarction provided the number of injected is nor less than 10(6).
    Zhonghua yi xue za zhi 07/2007; 87(22):1523-6.