Keqiang Wang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (34)96.52 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To evaluate geometrical and volume changes of membranous vestibular labyrinths in guinea pigs after endolymphatic hydrops (EH). Methods: The membranous labyrinths of normal guinea pigs and of those with EH for 4 and 8 weeks were reconstructed after being scanned using micro-computed tomography subseqent to being stained in osmium tetroxide (OsO4). The diameters and volumes of the semicircular ducts, ampullae, utricles and saccules were measured based on the three-dimensional models. Results: The diameters of the ampullae and utricles of EH guinea pigs were greater than those of the normal guinea pigs, while there were no significant differences in the diameters of the semicircular ducts among all groups. The volumes of ampullae, utricles and saccules of the EH groups were greater than those of the control group, but there were no changes in volumes of semicircular ducts after EH. Conclusion: The dilations of the membranous vestibular labyrinth in guinea pigs with EH mainly occur at the ampullae, utricles and saccules. © 2013 S. Karger AG, Basel.
    ORL 06/2013; 75(2):108-116. · 1.10 Impact Factor
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    ABSTRACT: Taurine, a conditionally essential amino acid, plays a critical role in cardiovascular function. Here we examined the effect of taurine on mitochondria and endoplasmic reticulum in rat cardiomyocytes during glucose deprivation (GD). Data showed that cell viability, intracellular taurine contents, and taurine transporter expression were decreased during GD. In contrast, an increase in reactive oxygen species and intracellular Ca(2+) contents was observed. GD also caused disrupted mitochondrial membrane potential, apoptotic cell death, and dissociation of unfolded protein response (UPR)-relative proteins in cardiomyocytes. Signal transduction analysis showed that Bcl-2 family protein balance was disturbed, caspase-12 was activated and UPR-relative protein levels were up-regulated. Moreover, pre-treatment with 80 mM exogenous taurine attenuated GD effect in cardiomyocytes. Our results suggest that taurine have beneficial effects on inhibiting mitochondria-dependent cell apoptosis and UPR-associated cell apoptosis and might have clinical implications on acute myocardial infarction in future.
    Acta Biochimica et Biophysica Sinica 05/2013; 45(5):359-67. · 1.81 Impact Factor
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    ABSTRACT: Magnetic resonance spectroscopy (MRS) is a unique non-invasive method for detecting cardiac metabolic changes. However, MRS in cardiac diagnosis is limited due to insensitivity and low efficiency. Taurine (Tau) is the most abundant free amino acid in the myocardium. We hypothesized that Tau levels may indicate myocardial ischemia and early infarction. Sprague-Dawley rats were divided into seven groups according to different time points during the course of myocardial ischemia, which was induced by left anterior descending coronary artery ligation. Infarcted myocardial tissue was obtained for high-resolution magic angle spinning (1)H nuclear magnetic resonance (NMR) analysis. Results were validated via high-performance liquid chromatography. The Tau levels in the ischemic myocardial tissue were reduced significantly within 5 min compared with those in the control group (relative ratio from 20.27±6.48 to 8.81±0.04, P<0.05) and were maintained for 6 h post-ischemia. Tau levels declined more markedly (56.5%) than creatine levels (48.5%) at 5 min after ligation. This suggests that Tau may have potential as an indicator in the early detection of myocardial ischemia by (1)H MRS.
    Experimental and therapeutic medicine 03/2013; 5(3):683-688. · 0.34 Impact Factor
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    ABSTRACT: Naoxintong (NTX), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosis-related diseases. Here, we tested the hypothesis that the anti-atherosclerosis effects of NTX might be mediated by suppressing maturation of dendritic cells (DCs) in a mice model of atherosclerosis.. LDLR-/- mice fed a high-fat diet were treated with placebo, NTX (0.7g/kg/d, oral diet) or simvastatin (100mg/kg/d, oral diet) for 8 weeks, respectively. NTX treatment significantly reduced plasma triglyceride (112±18 mg/dl vs. 192±68 mg/dl, P<0.05) and total cholesterol (944±158 mg/dl vs. 1387±208 mg/dl, P<0.05) compared to placebo treatment. Vascular lesions were significantly smaller and macrophage content and amount of DCs in plaques were significantly less in NTX and simvastatin groups than in placebo group (all P<0.05). In addition, plasma levels of splenic DC membrane molecules (CD40, CD86 and CD80) and IL-12p70 were significantly lower in NTX and simvastatin groups than in placebo group. In conclusion, NTX protects against atherosclerosis through lipid-lowering and inhibiting DCs maturation in this mice model of atherosclerosis.
    Current pharmaceutical design 02/2013; · 4.41 Impact Factor
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    ABSTRACT: Rho-associated kinase (ROCK) plays a critical role in pressure overload-induced left ventricular remodelling. However, the underlying mechanism remains unclear. Here, we reported that TGF-β1-induced ROCK elevation suppressed BMP-2 level and strengthened fibrotic response. Exogenous BMP-2 supply effectively attenuated TGF-β1 signalling pathway through Smad6-Smurf-1 complex activation. In vitro cultured cardiomyocytes, mechanical stretch up-regulated cardiac TGF-β1, TGF-β1-dependent ROCK and down-regulated BMP-2, but BMP-2 level could be reversed through blocking TGF-β1 receptor by SB-431542 or inhibition of ROCK by Y-27632. TGF-β1 could also activate ROCK and suppress endogenous BMP-2 level in a dose-dependent manner. Knock-down BMP-2 enhanced TGF-β1-mediated PKC-δ and Smad3 signalling cascades. In contrast, treatment with Y-27632 or SB-431542, respectively suppressed ROCK-dependent PKC-δ and Smad3 activation, but BMP-2 was only up-regulated by Y-27632. In addition, BMP-2 silencing abolished the effect of Y-27632, but not SB-431542 on suppression of TGF-β1 pathway. Further experiments showed that Smad6 Smurf1 interaction were required for BMP-2-evoked antagonizing effects. Smad6 overexpression attenuated TGF-β1-induced activation of PKC-δ and Smad3, promoted TGF-β RI degradation in BMP-2 knock-down cardiomyocytes, and could be abolished after knocking-down Smurf-1, in which Smad6/Smurf1 complex formation was critically involved. In vivo data showed that pressure overload-induced collagen deposition was attenuated, cardiac function was improved and TGF-β1-dependent activation of PKC-δ and Smad3 was reduced after 2 weeks treatment with rhBMP-2(0.5 mg/kg) or Y-27632 (10 mg/kg) in mice that underwent surgical transverse aortic constriction. In conclusion, we propose that BMP-2, as a novel fibrosis antagonizing cytokine, may have potential beneficial effect in attenuating pressure overload-induced cardiac fibrosis.
    Journal of Cellular and Molecular Medicine 01/2012; 16(10):2301-10. · 4.75 Impact Factor
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    ABSTRACT: To explore the relationship between three-dimensional (3-D) reconstruction of regenerated fibers and functional recovery after mastoid segment of facial nerve was repaired with either end-to-end anastomosis or autogenous great auricular nerve grafting. Thirty healthy adult New Zealand white rabbits were randomly divided into two groups: one was end-to-end anastomosis group and another was autogenous great auricular nerve grafting group. Only mastoid segment of right facial nerve of each animal was dissected and the contralateral nerve was as a control. Electromyogram (EMG) were recorded from 5 animals of each group at the 30th d, 90th d and 120th d after operation. After that the nerves were extracted, fixed, decalcified and embedded in paraffin. Samples was sectioned serially at 6 microm and stained with special trichrome stain. All the imagines were imported into Mimics software to reconstruct the 3-D model. The significant differences were found in the regenerate fibers on 30 th d,and were found in amplitude of EMG on 30 th d and 90 th d. The image of 3-D reconstruction showed that the myelin sheath were thickening, connected from proximal to the distal gradually after repair. The 3-D reconstruction of regenerated nerve fibers partly conformed to the functional recovery after facial nerve trunk was repaired. The functional recovery of facial nerve was related with both the quantity and the quality of regenerated nerve fibers.
    Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology 10/2011; 25(19):895-8.
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    ABSTRACT: Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). h-monDC were derived by incubating purified human monocytes with GM-CSF and IL-4. h-monDC were pre-incubated with or without Sal B and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of PPARγ siRNA. Expression of h-monDC membrane molecules (CD40, CD86, CD1a, HLA-DR) were analysed by FACS, cytokines were measured by elisa and the TLR4-associated signalling pathway was determined by Western blotting. Ox-LDL promoted h-monDC maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production; and up-regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPARγ activation and promoted PPARγ nuclear translocation, attenuated ox-LDL-induced up-regulation of TLR4 and myeloid differentiation primary-response protein 88 and inhibited the downstream p38-MAPK signalling cascade. Knocking down PPARγ with the corresponding siRNA blocked these effects of Sal B. Our data suggested that Sal B effectively suppressed maturation of h-monDC induced by ox-LDL through PPARγ activation.
    British Journal of Pharmacology 06/2011; 164(8):2042-53. · 5.07 Impact Factor
  • Caiqin Wu, Keqiang Wang, Lin Yang, Pei-Dong Dai
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    ABSTRACT: This paper presents and explains the procedure for creating three-dimensional (3D) finite element (FE) model of membranous vestibular labyrinth of guinea pig for numerical analysis. The model of membranous vestibular labyrinth was built from a series of micro computer tomography (micro-CT) images using MIMICS software. In order to visualize the membranous labyrinth in the micro-CT, the specimen was stained with Osmium tetroxide (OsO4) solution. An accurate 3D FE model of membranous vestibular labyrinth was built for computational fluid dynamics (CFD) and FE analysis.
    4th International Conference on Biomedical Engineering and Informatics, BMEI 2011, Shanghai, China, October 15-17, 2011; 01/2011
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    ABSTRACT: Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in experimental heart failure models, but the underlying mechanism remains largely unknown. In this study, we evaluated whether rhNRG-1 could improve cardiac function via the cardiac myosin light chain kinase/myosin light chain 2 ventricular (cMLCK/MLC-2v) pathway in rats with myocardial infarction (MI). Rats with MI were intravenously infused with rhNRG-1 (5 µg/kg/h) for 7 days through osmotic pumps. The mechanism of action of rhNRG-1 was investigated by assaying the non-infarcted myocardium with gene chips. The cMLCK expression, phosphorylated MLC-2v and cardiac function were significantly up-regulated, as assessed by real-time PCR, Western blot and echocardiography, in those animals treated with rhNRG-1. Moreover, the restoration of rhNRG-1-induced sarcomeric organization in serum-free cultured neonatal rat cardiomyocytes with rhNRG-1 was inhibited by cMLCK RNA interference or ML-7, an inhibitor of MLCKs. Adenovirus containing the rat cMLCK coding region was injected into non-infarcted myocardium, and cardiac function was monitored using echocardiography and a haemodynamic machine. The dP/dt and fractional shortening decreasing significantly after MI, and improved by 15.7 and 32.1%, respectively, following local cMLCK application (all P < 0.05). Our results suggest that cMLCK is a downstream effector of rhNRG-1 involved in rhNRG-1-induced cardiac function improvement, and that myocardial cMLCK up-regulation can improve cardiac function in rats with MI.
    Cardiovascular Research 11/2010; 88(2):334-43. · 5.81 Impact Factor
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    ABSTRACT: Endothelial cells of arteries (AEC) have a strikingly greater responsiveness to atherosclerosis factors than venous endothelial cells (VEC). However, the reasons for this phenomenon remain unclear. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an important role in regulating embryonic arterial-venous differentiation. We therefore investigate whether COUP-TFII is related to this different susceptibility between AEC and VEC. It is first confirmed that COUP-TFII is expressed in VEC but not in AEC in the adult. Using a siRNA strategy, we identified the expression of Jagged1 and Notch1 in cultured human VEC, which usually exist only in AEC, after knocking down of COUP-TFII. To further elucidate the role of COUP-TFII, we performed DNA microarrays in VEC transfected with the siRNA of COUP-TFII and subsequently stimulated with angiotensin II (AngII) and compared the expression profiles of 112 genes involved in various atherosclerosis-related pathways. The results indicated that expression of atherogenic genes was significantly upregulated after AngII stimulation in VEC transfected with COUP-TFII siRNA. Moreover, in vitro cell functional assay showed that knockdown of COUP-TFII in VEC increased not only basal but also AngII-induced cell adhesions. These results demonstrate that COUP-TFII suppresses the susceptibility of VEC to atherosclerosis through controlling the expression of various atherosclerosis-related molecules.
    Journal of Cellular Biochemistry 11/2010; 112(1):256-64. · 3.06 Impact Factor
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    ABSTRACT: Until now there was no systematic review concerning the chronic effects of intracoronary bone marrow-derived cell (BMC) transplantation in patients with acute myocardial infarction (MI). Improvement of cardiac function in patients with acute MI post BMC transplantation might last longer than 12 months. We searched MEDLINE, EMBASE, and the Cochrane database through June 2009. Eligible studies were randomized controlled trials of intracoronary BMC transfer in acute MI patients with follow-up duration equal to or longer than 12 months. A total of 8 trials involving 725 participants were identified. Compared with controls, BMC transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.37% (95% confidence interval [CI]: 2.66%-6.08%; P < 0.00001), reduced left ventricular end-diastolic volume (LVEDV) by 5.71 mL (95% CI: 2.03-9.40 mL; P = 0.002), left ventricular end-systolic volume (LVESV) by 8.94 mL (95% CI: 4.22-13.66 mL; P = 0.0002), and infarct size by 2.42% (95% CI: 1.33%-3.51%, P < 0.00001). Bone marrow-derived cell treatment also significantly reduced the risk of death (relative risk [RR]: 0.33, 95% CI: 0.13-0.89; P = 0.03), while the risk of reinfarction was similar between the 2 groups (RR: 0.62, 95% CI: 0.09-4.12; P = 0.62). Subgroup analysis showed that the BMC transplantation-induced LVEF increase was more significant in patients age < 55 and with cells transferred 6 or 7 days after MI. Beneficial effects of intracoronary BMC transplantation could last more than 12 months in acute MI patients.
    Clinical Cardiology 06/2010; 33(6):353-60. · 1.83 Impact Factor
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    ABSTRACT: TongXinLuo (TXL) is a traditional Chinese herbal medicine with multiple vasoprotective activities. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TXL on oxidized low-density lipoprotein (OX-LDL)-induced maturation and immune function of DCs. Human monocyte-derived DCs were incubated with TXL or ciglitazone and were subsequently stimulated with OX-LDL to induce maturation. Similar to ciglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, TXL could significantly reduce the maturation-associated markers induced by OX-LDL, such as CD40, CD86, CD1a, and human leukocyte antigen-DR; improved the endocytotic function; and decreased secretions of cytokine interleukin-12 and tumor necrosis factor alpha. These inhibitory effects of TXL could be partly reversed by silencing the expression of PPAR gamma in DCs. In conclusion, TXL could inhibit OX-LDL-induced maturation of DCs through activating PPAR gamma pathway.
    Journal of cardiovascular pharmacology 05/2010; 56(2):177-83. · 2.83 Impact Factor
  • American Journal of Cardiology - AMER J CARDIOL. 01/2010; 105(9).
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    ABSTRACT: Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial-specific enzyme, has been proved to be involved in oxidative stress-induced cell apoptosis, while little is known in cardiomyocytes. This study was aimed at investigating the role of ALDH2 in antimycin A-induced cardiomyocytes apoptosis by suppressing ALDH2 activity with a specific ALDH2 inhibitor Daidzin. Antimycin A (40μg/ml) was used to induce neonatal cardiomyocytes apoptosis. Daidzin (60μM) effectively inhibited ALDH2 activity by 50% without own effect on cell apoptosis, and significantly enhanced antimycin A-induced cardiomyocytes apoptosis from 33.5±4.4 to 56.5±6.4% (Hochest method, p<0.05), and from 57.9±1.9 to 74.0±11.9% (FACS, p<0.05). Phosphorylation of activated MAPK signaling pathway, including extracellular signal-regulated kinase (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38 was also increased in antimycin A and daidzin treated cardiomyocytes compared to the cells treated with antimycin A alone. These findings indicated that modifying mitochondrial ALDH2 activity/expression might be a potential therapeutic option on reducing oxidative insults induced cardiomyocytes apoptosis.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12/2009; 65(8):590-3. · 2.24 Impact Factor
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    ABSTRACT: To systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus. We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months. 7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83-1.02, p=0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85-1.06; p=0.33), cardiovascular mortality (0.95, 95% CI 0.71-1.27; p=0.71), stroke (0.83, 95% CI 0.63-1.10; p=0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65-1.11; p=0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70-8.61; p=0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men. In patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.
    Diabetes research and clinical practice 10/2009; 87(2):211-8. · 2.74 Impact Factor
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    ABSTRACT: Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI). Timing of BMSC administration might play an important role in the therapeutic response in AMI patients. A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine (EBM) databases was made on randomized controlled trials with at least 3-month follow-up data for patients with AMI undergoing emergent percutaneous coronary intervention (PCI) and receiving intracoronary BMSC transfer thereafter. A total of 7 trials with 660 patients were available for analysis. Compared to baseline level, BMSC transfer at 4 to 7 days post-AMI significantly improved left ventricular ejection fraction (LVEF; 4.63% increase, 95% confidence interval [CI]: 1.00%-8.26%, P = 0.01), reduced left ventricular (LV) end-systolic dimensions (95% CI: - 0.53 - 0.02, P = 0.03), decreased the incidences of revascularization (odds ratio [OR]: 0.60, 95% CI: 0.37-0.97, P = 0.04), decreased the cumulative clinical events of death or recurrent myocardial infarction (OR: 0.32, 95% CI: 0.11-0.95, P = 0.04), and decreased culprit artery restenosis or ventricular arrhythmia (OR: 0.59, 95% CI: 0.36-0.96, P = 0.03) however these improvements did not reach statistical significance in emergent transfer trials (within 24 hour post-AMI). Compared with emergent transfer, intracoronary BMSC therapy at 4 to 7 days also significantly reduced the incidence of revascularization (P for interaction = 0.02). BMSC transfer at 4 to 7 days post-AMI was superior to that within 24 hours in improving LVEF, decreasing LV end-systolic dimensions, and reducing the incidence of revascularization.
    Clinical Cardiology 09/2009; 32(8):458-66. · 1.83 Impact Factor
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    ABSTRACT: Atherosclerosis is an inflammatory disease characterized by extensive remodelling of the extracellular matrix architecture of the arterial wall. Recent data suggested the participation of lysosomal cysteine proteases such as cathepsin S (CTSS) in atherogenesis. The G/A polymorphism at nucleotide -25 was reported to be located in the promoter of the CTSS gene. The aim of this study was to observe the association between CTSS -25G/A polymorphism and the risk of coronary heart disease (CHD) in a Chinese population sample. The polymerase chain reaction and restriction digestion methods were performed to screen the CTSS gene -25G/A polymorphism in a Chinese population sample with (n = 659) or without CHD (n = 352). Traditional risk factors for CHD were obtained simultaneously. The frequencies of the G and A allele in the total population was 0.630 and 0.370, respectively. The frequencies of -25G/A polymorphism in the CTSS gene (G: 0.626 vs. 0.633, P > 0.05; A: 0.374 vs. 0.367, P > 0.05) and the genotype distribution (G: 83.4 vs. 85.3, P > 0.05; A: 58.0 vs. 58.5, P > 0.05) were similar between CHD patients and control subjects. Moreover, CTSS genotype was not associated with severity of coronary stenosis (P > 0.05) in CHD patients. The CTSS -25G/A polymorphism was not related with CHD in our Chinese population sample.
    Acta cardiologica 06/2009; 64(3):393-6. · 0.61 Impact Factor
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    ABSTRACT: The aim of the study was to evaluate the association between beta-fibrinogen gene -455G/A polymorphism and the plasma fibrinogen level in Chinese patients with different subtypes of coronary heart disease (CHD). We investigated beta-fibrinogen gene -455G/A polymorphism and plasma fibrinogen level in non-CHD control subjects (n = 466) and CHD patients (n = 1,019) including patients with stable angina pectoris (SAP) (n = 674), and acute coronary syndrome (ACS) (n = 345). Increased plasma fibrinogen levels were observed in the CHD groups compared with the control subjects (ACS: 380.92 +/- 92.35 mg/dl, SAP: 352.49 +/- 94.89 mg/dl, control: 311.72 +/- 87.09* mg/dl, *P < 0.001 vs. ACS and SAP). Individuals with the -455A/A genotype were associated with the highest plasma fibrinogen in the control subjects (P < 0.001) and patients with SAP (P < 0.001) but not in patients with ACS (P > 0.05). Allele frequency and genotype distribution were similar among the three groups (P = 0.314). This study demonstrated that elevated plasma fibrinogen level is related to increased CHD risk. The presence of -455A allele is significantly associated with higher fibrinogen in non-CHD control subjects and SAP patients but not in ACS patients while -455G/A polymorphism is not a risk factor for CHD in the Chinese population.
    Acta cardiologica 06/2009; 64(3):357-61. · 0.61 Impact Factor
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    ABSTRACT: Determining which time point is optimal for bone marrow-derived cell (BMC) transplantation for acute myocardial infarction (AMI) has attracted a great deal of attention. Studies have verified the interaction between cell treatment effect and transfer timing and have suggested that the optimal time frame for BMC therapy is day 4 to day 7 after AMI. However, the potential mechanism underlying the time-dependent therapeutic response remains unclear. Recently, a growing body of in vitro evidence has suggested that stem cells are able to feel and respond to the stiffness of their microenvironment to commit to a relevant lineage, indicating that soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Simultaneously, considering the fact that the myocardium post-infarction experiences a time-dependent stiffness change from flexible to rigid as a result of myocardial remodelling following tissue necrosis and massive extracellular matrix deposition, we presume that the myocardial stiffness within a certain time frame (possibly day 4-7) post-AMI might provide a more favourable physical microenvironment for the phenotypic plasticity and functional specification of engrafted BMCs committed to some cell lineages, such as endothelial cells, vascular smooth muscle cells or cardiomyocytes. The beneficial effect facilitates angiogenesis and myocardiogenesis in the infarcted heart, and subsequently leads to more amelioration of cardiac functions. If the present hypothesis were true, it would be of great help to understand the mechanism underlying the optimal timing for BMC transplantation and to establish a direction for the time selection of cell therapy.
    Journal of Cellular and Molecular Medicine 03/2009; 13(4):660-3. · 4.75 Impact Factor
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    ABSTRACT: Increased susceptibility to dilated cardiomyopathy has been observed in patients carrying mutations in the SCN5A gene, but the underlying mechanism remains unclear. In this study, we identified and characterized, both in vitro and clinically, an SCN5A mutation associated with familial progressive atrioventricular block of adult onset and dilated cardiomyopathy in a Chinese family. Among 32 family members, 5 were initially diagnosed with atrioventricular block after age 30; 4 were studied, 3 of whom later developed dilated cardiomyopathy. We found a heterozygous single-nucleotide mutation resulting in an amino acid substitution (A1180V) in all studied patients and in 6 other younger unaffected members but not in 200 control chromosomes. When expressed with the beta1 subunit, the mutated channels exhibited a -4.5-mV shift of inactivation with slower recovery leading to a rate-dependent Na(+) current reduction and a moderate increase in late Na(+) current. Clinical study revealed that although QRS duration decreased with increasing heart rate in noncarrier family members, this change was blunted in unaffected carriers whose ECG and heart function were normal. Resting corrected QT interval of unaffected carriers was significantly longer than that of noncarriers, even though it was still within the normal range. A1180V expresses a mild Na(+) channel phenotype in vitro and a corresponding clinical phenotype in unaffected mutation carriers, implying that A1180V caused structural heart disease in affected carriers by disturbing Na(+) influx and, hence, cellular Na(+) homeostasis. The high penetrance of A1180V suggests this phenotype as a high risk factor for dilated cardiomyopathy with preceding atrioventricular block.
    Circulation Arrhythmia and Electrophysiology 06/2008; 1(2):83-92. · 5.95 Impact Factor