Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.

Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-αcross-talk and cardioprotection

Background Vascular endothelial growth factor （VEGF） is one of major mediators of angiogenesis and survival factor in some tissue, however, its direct effects on cardiomyocytes remain poorly understood. Methods Rat neonatal ventricular myocytes were cultured in vitro. Akt phosphorylation was measured by Western blotting; the expression of stromal cell-derived factor α（SDF-1α）/CXCR4 axis was evaluated by real-time PCR and Western blotting. LY294002 and AMD3100 were used to interfere with the signaling of VEGF and SDF-1α/CXCR4 axis. Cardiac myocytes viability and injury were evaluated by trypan blue staining and lactate dehydrogenase （LDH） release. Results Treatment of neonatal rat ventricular myocytes with VEGF induced phosphorylation of Akt in a dose and FIk-1 dependent manner. VEGF attenuated H202 induced cardiac myocyte death. The phosphoinositol-3-kinase （PI3K） inhibitor, LY294002 and FIk-1 antibody abolished the beneficial effects of VEGF on H202 induced cell death. In the mean time SDF-1α-CXCR4 axis was up-regulated by VEGF through PI3K-Akt signaling and contributed to the protective effects of VEGF on H202 induced cell death. Interestingly, SDF-1α also promoted production of VEGF in cultured cardiac myocytes and LY294002 reversed the up-reguLation of VEGF induced by SDF-1α. Conclusion VEGF has direct protective effects on cardiomyocytes; a crosstalk between VEGF and SDF-1α through PI3K-Akt serves a survival role in cardiomvocvtes in vitro.

Expression of stromal cell-derived factor-1 in diabetic retinopathy

Background Neovascularization can cause vision loss in proliferative diabetic retinopathy （PDR） and may be affected by many factors. Stromal cell-derived factor-1 （SDF-1） is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor （VEGF） in the eyes with diabetic retinopathy. Methods The levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole （IMH）. Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry. Results The vitreous concentration of VEGF was significantly higher in eyes with PDR （（2143.7~1685.21） pg/ml） than in eyes with IMH （（142.42~72.83） pg/ml, P 〈0.001）. The vitreous level of SDF-1 was also significantly higher in eyes with PDR （（306.37~134.25） pg/ml） than in eyes with IMH （（86.91~55.05） pg/ml, P 〈0.001）. The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation （PRP） could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR （r=0.61, P 〈0.001）. The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes. Conclusions SDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.

The impact of hypoxic-ischemic brain injury on stem cell mobilization,migration,adhesion,and proliferation

Neonatal hypoxic-ischemic encephalopathy continues to be a significant cause of death or neurodevelopmental delays despite standard use of therapeutic hypothermia.The use of stem cell transplantation has recently emerged as a promising supplemental therapy to further improve the outcomes of infants with hypoxic-ischemic encephalopathy.After the injury,the brain releases several chemical mediators,many of which communicate directly with stem cells to encourage mobilization,migration,cell adhesion and differentiation.This manuscript reviews the biomarkers that are released from the injured brain and their interactions with stem cells,providing insight regarding how their upregulation could improve stem cell therapy by maximizing cell delivery to the injured tissue.

基质细胞衍生因子-1、趋化因子受体4及血管内皮生长因子在小儿肾母细胞瘤中的表达

目的探讨基质细胞衍生因子-1(SDF-1)、趋化因子受体4(CXCR4)和血管内皮生长因子(VEGF)在小儿肾母细胞瘤中的表达及其与临床特征的关系。方法收集郑州大学第一、三附属医院2003年5月-2008年5月手术切除经病理证实为肾母细胞瘤的石蜡标本30例。男13例,女17例;年龄4个月～7岁。其中预后良好组织型22例;预后不良组织型8例,以细胞质染成棕黄色为阳性细胞,以染色强度和阳性瘤细胞百分比的乘积作为阳性和阴性判断标准。对照组12例取瘤旁正常肾组织标本。2组均行HE染色,采用SPSS13.0软件进行统计学分析。结果VEGF、CXCR4和SDF-1在肾母细胞瘤中的阳性表达率分别为63.33%、70.0%、53.33%,而在瘤旁正常肾组织中的阳性表达率分别为25.0%、8.3%、16.7%。VEGF、CXCR4和SDF-1在肾母细胞瘤中的表达均明显高于瘤旁正常肾组织(Pa<0.05),3者在临床分期Ⅲ～Ⅳ期和预后不良组织型组及有淋巴转移组的肾母细胞瘤中的表达明显高于在临床分期Ⅰ～Ⅱ期和预后良好组织型及无淋巴结转移的肾母细胞瘤中的表达(Pa<0.05)。相关分析显示CXCR4与VEGF、SDF-1的阳性表达均呈正相关,SDF-1与VEGF的阳性表达亦呈正相关。肾母细胞瘤中CXCR4、SDF-1和VEGF的表达与肿瘤的淋巴结转移、病理分型及临床分期有相关性,而与性别无相关性。结论VEGF、SDF-1及CXCR4与肾母细胞瘤的发展、预后有关,参与了肿瘤血管的生成及肿瘤的增殖侵袭,对于评估患儿预后及靶向治疗肾母细胞瘤具有一定意义。

Effect of Fufang Xueshuantong Capsule(复方血栓通胶囊) on A Rat Model of Retinal Vein Occlusion

Objective：To establish a retinal vein occlusion（RVO） animal model and observe the therapeutic effect of a Chinese herbal composition（Fufang Xueshuantong Capsule,复方血栓通胶囊,FXC） in ischemic retinal disease.Methods：Fifteen adult male Sprague-Dawley rats underwent laser photothrombosis to induce RVO on their right eyes and were subsequently randomized to receive FXC（the intervention group,n=7） or placebo treatment（the control group,n=8）.Fundus fluorescein angiography was performed after 2,4 and 8 weeks of treatment.Real-time reverse transcription-PCR was used to quantify the mRNA expression of vascular endothelial growth factor（VEGF） and stromal cell-derived factor-1（SDF-1）.The main outcomes were the mRNA copies of VEGF and SDF-1 and the counts of RVO signs.Results：Laser photothrombosis procedure induced typical lesions of RVO,including hemorrhage,leakage,retinal detachment,capillary non-perfusion,filling defect of retinal vessels,and lateral circulation/dilation of small vessels.The retinal lesions were associated with an increased expression of VEGF（P0.05）.No significant change of SDF-1 expression was noticed.Compared with the control group,the intervention group had numerically fewer RVO lesions at week 2（1.71±0.76 vs.3.50±1.51,t=-2.82,P0.05）.The benefit of intervention remained at weeks 4 and 8.Conclusions：A rat model of laser photothrombosis-induced RVO was established and an increase in the VEGF expression was observed in the retinal lesion.The FXC had therapeutic benefit in improving retinal lesions in the rat model of RVO.