Effects of 2,5-hexanedione on angiogenesis and vasculogenesis in chick embryos

n-Hexane is widely used in industry and its metabolite, 2,5-hexanedione (2,5-HD), has been implicated as a neural toxin in the developing fetus. Using the chick embryo model, we have previously revealed the neurotoxicity of 2,5-HD during development and established that high dose of 2,5-HD was embryo lethal. In view of the close linkage in biology for neurogenesis and angiogenesis, we speculated that it was most likely caused by cardiovascular dysplasia, therefore in this study, we investigated the effects of 2,5-HD on the development of the vasculature, which involves vasculogenesis and angiogenesis. Using gastrulating chick embryos as a model, we demonstrated that the hemangioblasts (precursor of hematopoietic and endothelial cells) migrated to the area opaca where they form the blood islands. However, this process was impaired when the embryos were treated with 2,5-HD, suggesting that 2,5-HD is capable of impairing vasculogenesis. To study the effect of 2,5-HD exposure on angiogenesis, we used the chick yolk-sac membrane (YSM) and chorioallantoic membrane (CAM) models. We found that, at low (0.02 M) concentration, 2,5-HD stimulated angiogenesis while at higher concentrations (>0.1 M) it inhibited this process. This biphasic response of angiogenesis to 2,5-HD exposure was found to be associated with altered expression of the VEGF-R, FGF-2 and angiogenin. Moreover, we also determined that 2,5-HD exposure increased the reactive oxygen species (ROS) production. In conclusion, 2,5-HD could induce dysplasia in the developing vasculature, which in turn could cause extravascular hemolysis and the embryos to die.     

生长抑素对胃癌VEGFs和VEGF受体影响的实验研究

目的探讨VEGFs/VEGFRs与胃癌的恶化及不良预后的关系。方法将60例患者随机分成生长抑素预处理组和安慰剂组,采用酶联免疫法、实时定量PCR法和免疫组化法检测VEGF水平。结果生长抑素预处理组血清VEGF水平明显下降,但mRNA水平并无明显变化,并且血清VEGF水平下降是由于蛋白降解而非mRNA转录下降引起的。同时,预处理组VEGF受体-3蛋白明显下降。结论生长抑素通过下调血清VEGF水平和VEGF受体-3的表达,从而达到抗血管生成作用,为应用生长抑素治疗胃癌提供实验依据。     

Vascularization in tissue remodeling after rat hepatic necrosis induced by dimethylnitrosamine

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12 h after DMN injection and reached a peak in number at 36 h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.     

Left circumflex coronary artery to hepatic vein fistula: a case report and brief review of coronary vasculogenesis

Coronary artery fistulas are rare coronary artery anomalies. Their clinical significance varies from a long asymptomatic course to overt heart failure and death. They are often detected incidentally with diagnostic coronary angiograms. Cardiologists increasingly encounter coronary artery fistulas secondary to recent improvements in cardiovascular imaging modalities. Management is still controversial, especially in asymptomatic cases with less significant shunts. Here, we describe a 62-year-old woman with a left circumflex artery to hepatic vein fistula found on coronary angiography. The patient is being managed conservatively using nuclear imaging studies and echocardiographic evaluation.     

A new model of vasculogenesis and angiogenesis in vitro as compared with vascular growth in the avian area vasculosa

In cultures of dissociated quail epiblast the basic constituents of the vascular system, blood cells and endothelial cells can be induced by basic fibroblast growth factor (Flamme and Risau, Development, 116:435–439, 1992). As we show here, in those cultures three types of vascular plexus differentiate spontaneously under different culture conditions: At the 3rd day a vascular plexus appears in situ closely resembling the vascular plexus of the quail area opaca vasculosa (vasculogenesis). Vascular sprouts are formed, extending long filopodia at their tips. Such filopodia are shown to build the first intervascular bridges in the growing vascular plexus of the area vasculosa at embryonic day 3. Connections of filopodia turn out to be precursors of new capillaries interconnecting pre-existing blood vessels (angiogenesis). Two further types of in vitro capillary plexus differentiate in long term endothelial cell cultures derived from induced angioblasts. Whereas one closely resembles so-called angiogenesis in vitro, the third type comprises mainly multinucleated giant endothelial cells lining loop like capillaries and represents a differentiation of aging endothelial cell culture. Thus, the present in vitro model is an approach to the sequence of angioblast induction, vasculogenesis, and angiogenesis. © 1993 Wiley-Liss, Inc.     

Early formation of the vascular system in quail embryos

The relation between vascular development and translocation of the splanchnic mesodermal layers was studied in presomite to 20-somite quail embryos by scanning electron microscopy. In addition, serially sectioned embryos were stained immunohistochemically with monoclonal antibodies (αQH1 or αMB1) specific for endothelial and hemopoietic cells. By the formation of the foregut the anterior borders of the two splanchnic mesodermal layers of a presomite embryo are translocated to the lateral and ventral sides of the foregut and fuse in the ventral midline of a 4-somite embryo. Meanwhile the splanchnic mesoderm differentiates into a splanchnic mesothelial layer and a plexus of endothelial cells, facing the endoderm. From 4 somites onward the foregut is covered by a single endothelial plexus. At first the endothelial precursors bordering the anterior intestinal portal and those in the area of the ventral mesocardium lumenize, subsequently giving rise to the endocardium of the heart tube. Hereafter, the pharyngeal arch arteries and the dorsal aortae develop from the remaining precursors. During formation of the pharyngeal arches, the pharyngeal arch arteries maintain their connections with the splanchnic plexus through the developing ventral pharyngeal veins. After disappearance of the dorsal mesocardium, the midpharyngeal endothelial strand, which is a longitudinal strand of proendocardial cells, remains connected to the foregut. This strand will contribute to the formation of the pulmonary venous drainage into the left atrium. A bilateral accumulation of cardiac jelly developing between the promyocardium and proendocardial plexus only suggests that the heart develops from two tubes. The proendocardial layer, however, is not divided by the ventral mesocardium but initially forms just one endocardial heart tube. © 1993 Wiley-Liss, Inc.     

血管内皮细胞促进组织工程骨血管化的研究进展

组织工程骨的血管化问题严重制约了大块组织工程骨的发展和运用.血管内皮细胞对组织工程骨血管化具有重要促进作用,根据血管化过程中血管内皮细胞的来源不同,将血管化过程分血管发生和血管生成两种形式.成骨细胞和血管内皮细胞共同培养时可以相互促进生长.目前对组织工程骨血管化进行了血管内皮细胞新的来源,细胞混合培养和体内试验等方面的探索.     

Morphological and molecular aspects of physiological vascular morphogenesis

The cardiovascular system plays a crucial role in vertebrate development and homeostasis. Several genetic and epigenetic mechanisms are involved in the early development of the vascular system. During embryonal life, blood vessels first appear as the result of vasculogenesis, whereas remodeling of the primary vascular plexus occurs by angiogenesis. Many tissue-derived factors are involved in blood vessel formation and evidence is emerging that endothelial cells themselves represent a source of instructive signals to non-vascular tissue cells during organ development. This review article summarizes our knowledge concerning the principal factors involved in the regulation of vascular morphogenesis.