血管内皮生长因子在脑缺血中的保护机制

血管内皮生长因子（VEGF）是作用最强的血管生成因子之一。研究证明，在脑缺血动物脑内注入外源性VEGF能促进血管生成，但同时在缺血半暗带内会发生“盗血”现象。另一方面，VEGF对中枢神经系统具有神经发生、直接神经营养和神经保护等多重保护作用。从分子水平了解这些神经保护机制，更有益于临床开发治疗脑缺血的措施。     

血管内皮生长因子在脑缺血中的作用

血管内皮生长因子(vascular endothelial growth factor,VEGF)是一种重要的调节多种内皮功能的血管生长因子.脑缺血后,VEGF不仪能促进血管内皮细胞增殖和迁移,参与血管生成,增加血管通透性,而且在神经保护和神经发生等方面也起着重要作用.文章就VEGF在缺血性脑损伤中的作用进行了综述.     

血管再狭窄防治的新策略

血管内皮生长因子是特异性的强有力的促内皮生成因子，在缺血性疾病的治疗中它是重要的促进血管新生的因子，同时它还有抗再狭窄作用，这一作用与血管内皮生长因子介导的内皮修复密切相关。本文对血管内皮生长因子抗狭窄作用的机理及研究进展作一综述。     

血管内皮生长因子及其受体对缺血性脑血管病脑微血管生成作用机制研究进展

血管内皮生长因子及其受体具有促进内皮细胞增殖,加速新生血管形成,增加血管通透性等特点,它与缺血性脑血管病的发生发展密切相关。本文将从血管内皮生长因子及其受体的概况、诱导途径、在脑缺血损伤后血管生成中的利弊影响几方面对血管内皮生长因子／血管内皮生长因子受体系统作一综述,详述其在血管生成方面的调控机制、时空表达、细胞分布及剂量关系等特点,并对血管内皮生长因子在目前应用中遇到的问题及在未来临床中的应用前景予以分析。     

血管内皮生长因子与脑梗死

血管内皮生长因子(vascular endothelial growth factor,VEGF)是血管内皮细胞的一种特异性促分裂原,是最重要的促血管新生因子.VEGF在脑梗死后高度表达,在血管新生和神经保护中起着重要作用;同时,其过度表达也会使血管通透性增加,进而可能加重脑水肿.文章对VEGF及其受体与脑梗死的研究进展进行了综述.     

神经发生、血管内皮生长因子与血管性认知损害

神经发生是神经前体细胞自我增殖和分化产生新神经元的动态过程。研究证实,海马神经发生可改善认知功能,并且血管内皮生长因子(vascular endothelial growth factor, VEGF)在神经发生中发挥着重要的调控作用。文章就 VEGF 促进神经发生的机制以及神经发生改善血管性认知损害的作用进行了综述。     

高血压对怀孕期间的血管生成素和血红素氧合酶的影响

高血压和先兆子痫的病理生理机制涉及血管新生和内皮损伤/功能紊乱,表现在血浆中生长因子[血管内皮生长因子(vascular endothelial growth factor,VEGF)和VEGF受体1(sFlt-1)]与血管性血友病因子(von willebrand factor,vWF)水平异常。发生高血压和血管新生时,     

非小细胞肺癌术后组织中基质金属蛋白酶-2、-9和血管内皮生长因子表达及对血管生成的影响

非小细胞肺癌临床多见,其发生发展过程中血管生成具有重要价值[1].血管内皮生长因子(VEGF)是血管生成的重要促进因子,可以直接促进新生血管的增殖.基质金属蛋白酶(MMP)-2、-9是MMP家族的经典成员,对细胞外基质的降解有重要作用,近年的研究显示二者可能对血管生成有一定的促进作用[2].CD105是血管内皮的重要标记蛋白,可以成功地标记肿瘤中新生的血管.     

生长因子的协同作用与新血管形成的研究进展

缺血性疾病的血管重建不只依赖于血管新生,还需骨髓来源的前体细胞的参与.缺血本身不仅能动员血管前体细胞,而且能够增强它们向内皮细胞分化的能力.有许多生长因子如血管内皮生长因子、血小板源性生长因子等能募集骨髓来源的内皮前体细胞到血管重建部位.但是,缺血诱导的血管形成往往不能完全弥补外周血管病变和动脉闭塞所引起的血流减少,并且单一的生长因子作用也不能诱导成熟稳定的血管形成,同时易出现并发症而制约了其临床应用.因此如何利用生长因子动员血管前体细胞参与血管新生,并通过其协同作用形成稳定的功能性的血管成为研究的热点.本文就生长因子协同作用参与新血管形成方面作一综述.     

静脉注射携带缺氧诱导因子的内皮祖细胞对裸鼠缺血下肢血管新生的作用

目的探讨静脉注射携带缺氧诱导因子1α的内皮祖细胞对裸鼠缺血下肢血管新生的作用及机制。方法在体外将腺病毒介导人缺氧诱导因子1α基因入人外周血内皮祖细胞,观察转染后的内皮祖细胞在裸鼠缺血下肢局部的促血管新生作用,并探讨其可能的作用机制。结果转染腺病毒—缺氧诱导因子1α后的内皮祖细胞在细胞内有效并持续表达;移植异种腺病毒—缺氧诱导因子1α内皮祖细胞至Balb/c鼠缺血下肢后可见外源性内皮祖细胞定向作用于缺血部位;移植腺病毒—缺氧诱导因子1α内皮祖细胞组较对照组明显促进体内毛细血管数目增加(P<0.05);mRNA检测提示过表达缺氧诱导因子1α基因可上调其下游的基质细胞衍生因子、CXCR4因子(P<0.05),增加内皮祖细胞招募,同时促血管内皮生长因子水平上调(P<0.05)。结论在体内,转染腺病毒—缺氧诱导因子1α的内皮祖细胞可促进缺血下肢的局部血管新生,这种内皮祖细胞数量的增加可能与基质细胞衍生因子、CXCR4的招募及血管内皮生长因子的分泌增加有关。     

血管内皮生长因子用于治疗性血管生成的问题及对策

生理和病理性血管生成中,血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)是主要的血管生成因子。VEGF促血管生成的能力在动物和临床中已得到了广泛的研究。然而,越来越多的证据显示新生血管结构需要获得稳定,以避免水肿和形成血管瘤等不良反应。而且VEGF在促进血管生成的同时,也可能促进粥样斑块的生长。通过调节VEGF表达时间和表达量,或联合使用血小板衍生生长因子BB(plateletderivedgrowthfactorBB,PDGFBB)等“成熟”因子,有可能产生成熟的血管。导入不同基因到同一细胞以获得能同时表达“生长”和“成熟”因子的细胞,使细胞介导的基因转移在治疗性血管生成中具有独特价值。另一个可选择的策略是使用可调控多种血管生成因子表达的转录因子。     

Expression of VEGF(121) in gastric carcinoma MGC803 cell line

INTRODUCTION Vascular endothelial growth factor (VEGF) which is also known as vascular permeability factor (VPF) is a heparin-binding, dimeric polypeptide growth factor and a potent mitogen for endothelial cells.VEGF can stimulate the endothelial cell growth and enhance the motility through its two known receptors flt-1 and KDR[1]. Acting through these receptors, VEGF may stimulate angiogenesis and promote tumor progression. VEGF12l, as one of the four VEGF protein isoforms containing the least number of amino acids, has all the biological function of VEGF and is the ideal isoforms for further studying VEGF at molecular levels[2]. In this study, we cloned     

Vascular endothelial growth factor

An understanding of the mechanisms regulating growth and differentiation of vascular endothelial cells is very important for cardiovascular biology and medicine. Several potential regulators of angiogenesis have been identified, including acidic and basic fibroblast growth factors, epidermal growth factor, platelet-derived endothelial cell growth factor, transforming growth factors and β, and tumor necrosis factor (TNF-). Vascular endothelial growth factor (VEGF) is unique among these agents by virtue of its direct and specific mitogenic effects on endothelial cells combined with the fact that it is a secreted polypeptide. By alternative splicing of mRNA, VEGF may exist in four different isoforms that have similar biologic activities but differ markedly in their secretion pattern. VEGF is emerging as an important regulator of developmental and ovarian angiogenesis. Its action is purely paracrine as it is produced by a variety of cell types, but its receptors are only in endothelial cells. There is no evidence that endothelial cells in vivo produce VEGF. The VEGF mRNA is expressed at high level by a variety of human tumors, suggesting that VEGF may be a tumor angiogenesis factor. This hypothesis is supported by the finding that monoclonal antibodies specific for VEGF are able to suppress tumor growth in vivo. Therefore, VEGF antagonists may be used for the treatment of malignancies and, possibly, other angiogenic diseases. The VEGF protein has therapeutic potential as an inducer of neovascularization in conditions characterized by impaired tissue perfusion like obstructive atherosclerosis.     

VEGF gene alternative splicing: pro- and anti-angiogenic isoforms in cancer

Tumor growth and progression depend on angiogenesis, a process of new blood vessels formation from a preexisting vascular endothelium. Tumors promote angiogenesis by secreting or activating angiogenic factors that stimulate endothelial proliferation and migration and capillary morphogenesis. The newly formed blood vessels provide nutrients and oxygen to the tumor, increasing its growth. Thus, angiogenesis plays a key role in cancer progression and development of metastases. An important growth factor that promotes angiogenesis and participates in a variety of physiological and pathological processes is the vascular endothelial growth factor (VEGF-A or VEGF). Overexpression of VEGF results in increased angiogenesis in normal and pathological conditions. The existence of an alternative site of splicing at the 3′ untranslated region of the mRNA results in the expression of isoforms with a C-terminal region which are downregulated in tumors and may have differential inhibitory effects. This suggests that control of splicing can be an important regulatory mechanism of angiogenesis in cancer.     

Reversible modulations of neuronal plasticity by VEGF

Neurons, astrocytes, and blood vessels are organized in functional "neurovascular units" in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.     

Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis

Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation but also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C-gamma (PLC-gamma) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO), which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus, VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of VEGF.     

血管内皮生长因子与慢性阻塞性肺疾病的肺血管重构

血管内皮生长因子（VEGF）具有促进血管内皮细胞增殖和血管生成的作用。研究表明，VEGF在慢性阻塞性肺疾病（COPD）的肺血管重构中起着重要作用，进而加重其气道阻力和气道炎症，影响COPD的预后。如何使VEGF保持一个合适的水平有待于我们进一步的研究。     

Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression

The semaphorins and plexins comprise a family of cysteine-rich proteins implicated in control of nerve growth and development and regulation of the immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis, with some neoplasms producing SEMA4D in a manner analogous to vascular endothelial growth factor (VEGF) in order to attract Plexin-B1-expressing endothelial cells into the tumor for the purpose of promoting growth and vascularity. While anti-VEGF strategies have been the focus of most angiogenesis inhibition research, such treatment can lead to upregulation of pro-angiogenic factors that can compensate for the loss of VEGF, eventually leading to failure of therapy. Here, we demonstrate that SEMA4D cooperates with VEGF to promote angiogenesis in malignancies and can perform the same function in a setting of VEGF blockade. We also show the potential value of inhibiting SEMA4D/Plexin-B1 signaling as a complementary mechanism to anti-VEGF treatment, particularly in VEGF inhibitor-resistant tumors, suggesting that this may represent a novel treatment for some cancers.