血管内皮生长因子受体信号转导通路与肿瘤血管生成

血管内皮生长因子是促进血管生成的重要调节因子.它能促进内皮细胞增殖、迁移,阻止内皮细胞凋亡、管腔网状结构退化,增加血管渗透性.所有这些作用都是通过血管内皮生长因子受体信号转导通路实现的.它们在肿瘤血管生成、肿瘤生长中起着重要的作用.以血管内皮生长因子受体信号转导通路为靶点是开发肿瘤血管生成抑制剂的理想策略.     

解偶联蛋白2在内皮损伤及血管重构中的作用研究进展

心脑血管疾病是全球最主要的致死性疾病。活性氧(Reactive oxygen species,ROS)产生增多诱发血管内皮细胞损伤、平滑肌细胞迁移、增殖,是导致血管功能障碍、血管重构发生的重要机制。因此,氧化应激被认为是心脑血管疾病发生、发展的关键环节。但通过补充外源性抗氧化剂防治心脑血管疾病一直存在较大争议。机体可通过自身防御体系拮抗氧化应激,维持氧化-还原状态,如通过调控线粒体解偶联蛋白2(Uncoupling protein 2,UCP2)调节ROS生成,改善血管功能障碍及血管重构。本文就UCP2在内皮损伤及血管重构中的作用及机制展开综述,为深入探索这一潜在的防治心脑血管疾病的靶点提供信息。     

内皮细胞增殖抑制因子研究进展

内皮细胞过度增殖引起的病理性血管生成是肿瘤、类风湿性关节炎等发病的关键环节。内皮细胞增殖由血管内皮细胞生长因子等促血管生成因子提供促增殖信号,而新近发现的多种内皮增殖抑制因子,如血管内皮抑素、血管抑素、血小板反应蛋白-1、微囊蛋白1、某些microRNAs和某些抑癌基因等,则通过抑制促增殖信号、调节细胞周期、诱导细胞凋亡等途径下调内皮细胞的增殖及血管生成。内皮增殖抑制因子可望成为病理性血管生成防治的新靶点。     

内皮抑素在新生血管形成相关疾病中的作用机制研究进展

新血管形成是许多生理、病理过程的关键步骤,受血管形成促进因子和抑制因子的调节。内皮抑素是最重要的血管形成抑制因子之一,可在体外抑制血管内皮细胞的增殖、迁移和血管化,在动物模型中抑制新血管形成,对新生血管形成相关疾病,特别是肿瘤有治疗作用。关于内皮抑素抑制新血管形成的分子机制尚无定论,已有线索表明,它可通过与VEGF、MMP-2、整合素以及VEGF受体KDR等相互作用,从而抑制内皮细胞增殖、迁移或通过多种途径促进内皮细胞凋亡。本就内皮抑素作用的分子机制,及其作用于新血管形成相关疾病的最新研究成果进行综述。     

血管内皮细胞间紧密连接的研究进展

紧密连接是物质经旁细胞途径转运的结构和功能基础。近年来研究发现,在脑、视网膜、肺及肾等多个器官的微血管内皮细胞以及主动脉等大血管内皮细胞表达的紧密连接对维持血管稳态发挥了重要作用,一些细胞因子或环境刺激可通过调节紧密连接的表达、分布、结构和功能进而改变内皮通透性,从而影响血管及相应器官和组织的功能。本文重点综述了内皮细胞间紧密连接的研究进展,为防治与紧密连接相关的血管疾病提供新的思路。     

钙网蛋白在内皮细胞相关疾病中的病理生理作用

心脑血管病、糖尿病和肿瘤等内皮相关疾病严重威胁人类健康。内皮结构与功能的损伤是内皮相关疾病发病机制中至关重要的环节。内质网Ca2+结合蛋白钙网蛋白(calreticulin,CRT)调节内皮细胞增殖、黏附、迁移、凋亡等过程,参与肿瘤、糖尿病、心脑血管病等内皮相关疾病的发生、发展和转归。外源性CRT对肿瘤、眼部新生血管病变、慢性愈合不良性伤口和缺血性疾病具有潜在治疗作用。本文综述钙网蛋白对内皮细胞的调节及其在内皮相关疾病中的病理生理学作用。     

内皮-间质转化与心血管疾病的研究进展

内皮-间质转化(endothelial-to-mesenchymal transition,End MT)属于上皮-间质转化(epithelial-to-mesenchymal transition,EMT)的特殊类型,是内皮细胞在多种刺激因素作用下向间充质细胞转化的过程,在此过程中内皮细胞逐渐失去其形态和功能,获得增殖、迁移和合成胶原等间充质细胞表型特点.近来研究发现,内皮-间质转化在内皮功能调节,心肌、血管及瓣膜的发育和结构重塑等方面发挥着关键的作用,提示其在心血管疾病领域具有重要的研究意义.本文对内皮-间质转化的特点、功能、调节机制以及在心血管系统发育、心肌纤维化、肺动脉高压和动脉粥样硬化性血管重构等心血管疾病中的作用做一综述,以期为心血管疾病的防治提供新靶点.     

人造血管移植物自然内皮化的研究

人造血管移植作为自体血管代用品已被广泛使用了解内皮细胞的功能,来源,血管内皮化的过程,形成机理及影响内皮化的因素,对防治血栓形成,内膜增生,维持移植血管通畅率有重要意义。     

MicroRNA-126(miR-126)对血管调节的分子机制

脉管系统的结构,维护及重塑的精确调节对于血管的正常发育,组织损伤的应答和肿瘤的生长都是必不可少的。最近,越来越多的研究报道了非编码的RNAs,又叫做microRNAs调节内皮细胞对血管原刺激的应答反应。在体内,维持血管内皮细胞和血管的完整性方面miR-126是一种重要的血管生成信号调节因子。miR-126通过负性调控血管生长因子促进血管发生反应,这些血管因子包括血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)。因此,miR-126表达的靶向作用也许对于血管过多或缺乏引起的相关疾病开辟了一种新的治疗方法,这些发现也证实了单一miRNA能够调节血管的完整性及血管生成,为调整血管的形态和功能提供了一个新的靶点。本文就当前miR-126对血管的调节及分子机制进行综述。     

瞬时受体电位通道在心脑血管系统疾病中的研究进展

瞬时受体电位(TRP)通道是一类重要的非选择性阳离子通道,其家族成员众多,参与多种生理病理过程。其中,TRP通道的异常表达及功能改变与心脑血管疾病的发生发展密切相关。近年研究发现,通过拮抗或者激活TRP通道可以调节血管内皮和血管平滑肌功能,参与心脑血管疾病的调控。该文主要从TRP通道的结构及各亚家族蛋白基于血管内皮和血管平滑肌对心脑血管系统疾病的作用及机制作一综述,为心脑血管疾病的防治提供新思路。     

血管内皮细胞衰老与血管疾病

细胞衰老是指细胞在各种应激条件下出现周期阻滞,不可逆地丧失增殖能力,其形态、基因表达和功能都发生特定变化的过程。研究表明,血管内皮细胞衰老可以通过削弱血管功能,促进衰老相关血管疾病的发生发展。然而,有关内皮细胞衰老的发生机制以及内皮细胞衰老影响血管功能及衰老相关血管疾病的潜在机制尚待挖掘。本文从血管内皮细胞衰老相关的信号通路,以及血管内皮细胞衰老与血管功能和血管相关疾病（动脉粥样硬化、高血压和糖尿病血管并发症）的最新研究进展进行综述,为进一步认识血管疾病的发病机制,延缓血管衰老提供新的思路。     

Endothelial dysfunction as a cellular mechanism for vascular failure

The regulation of vascular tone, vascular permeability, and thromboresistance is essential to maintain blood circulation and therefore tissue environments under physiological conditions. Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart disease and stroke. We have proposed a novel concept termed "vascular failure" to comprehensively recognize the vascular dysfunction that contributes to the development of cardiovascular diseases. Vascular endothelial cells form the vascular endothelium as a monolayer that covers the vascular lumen and serves as an interface between circulating blood and immune cells. Endothelial cells regulate vascular function in collaboration with smooth muscle cells. Endothelial dysfunction under pathophysiological conditions contributes to the development of vascular dysfunction. Here, we address the barrier function and microtubule function of endothelial cells. Endothelial barrier function, mediated by cell-to-cell junctions between endothelial cells, is regulated by small GTPases and kinases. Microtubule function, regulated by the acetylation of tubulin, a component of the microtubules, is a target of atherogenic stimuli. The elucidation of the molecular mechanisms of endothelial dysfunction as a cellular mechanism for vascular failure could provide novel therapeutic targets of cardiovascular diseases.     

VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis

Within the vascular endothelial growth factor (VEGF) family of five subtypes, VEGF165 secreted by endothelial cells has been identified to be the most active and widely distributed factor that plays a vital role in courses of angiogenesis, vascularization and mesenchymal cell differentiation. Hair follicle stem cells (HFSCs) can be harvested from the bulge region of the outer root sheath of the hair follicle and are adult stem cells that have multi‐directional differentiation potential. Although the research on differentiation of stem cells (such as fat stem cells and bone marrow mesenchymal stem cells) to the endothelial cells has been extensive, but the various mechanisms and functional forms are unclear. In particular, study on HFSCs’ directional differentiation into vascular endothelial cells using VEGF165 has not been reported. In this study, VEGF165 was used as induction factor to induce the differentiation from HFSCs into vascular endothelial cells, and the results showed that Notch signalling pathway might affect the differentiation efficiency of vascular endothelial cells. In addition, the in vivo transplantation experiment provided that HFSCs could promote angiogenesis, and the main function is to accelerate host‐derived neovascularization. Therefore, HFSCs could be considered as an ideal cell source for vascular tissue engineering and cell transplantation in the treatment of ischaemic diseases.     

Apelin/APJ：血管功能调节因子和药物治疗新靶点

Apelin(APJendogenousligand)是血管紧张素Ⅱ1型受体相关蛋白(angiotensin receptor-like 1,APJ)的内源性配体.Apelin/APJ系统在机体内广泛分布,在众多血管系统表达水平较高,如心血管系统、肺血管系统等.研究发现,apelin可调节血管张力,促进血管平滑肌细胞增殖、视网膜血管新生以及单核细胞向内皮细胞黏附,促进肝门静脉和冠状动脉侧枝形成等.本文就apelin调节血管功能及其相关疾病(高血压、肺动脉高压、动脉粥样硬化、胶质瘤、肺癌、门静脉高压、糖尿病血管并发症等)进行综述,揭示了apelin与血管及其相关疾病的内在联系,表明apelin/APJ可作为血管疾病的治疗靶点.     

The Vascular Endothelium and Human Diseases

Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.     

Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease

Sphingosine-1-phosphate receptors (S1PRs) have an impact on the intestinal inflammation of inflammatory bowel disease (IBD) by regulating lymphocyte migration and differentiation. S1PR modulators as an emerging therapeutic approach are being investigated for the treatment of IBD. However, the role of S1PRs in intestinal vessels has not drawn much attention. Intestinal vascular damage is one of the major pathophysiological features of IBD, characterized by increased vascular density and impaired barrier function. S1PRs have pleiotropic effects on vascular endothelial cells, including proliferation, migration, angiogenesis and barrier homeostasis. Mounting evidence shows that S1PRs are abnormally expressed on intestinal vascular endothelial cells in IBD. Unexpectedly, S1PR modulators may damage intestinal vasculature, for example increase intestinal bleeding; therefore, S1PRs are thought to be involved in the regulation of intestinal vascular function in IBD. However, little is understood about how S1PRs regulate intestinal vascular function and participate in the initiation and progression of IBD. In this review, we summarize the pathogenic role of S1PRs in and the underlying mechanisms behind the intestinal vascular injury in IBD in order for improving IBD practice including S1PR-targeted therapies.     

综述: 影响血管内皮细胞自噬的因素及其相关机制探讨

自噬对维持细胞自身的稳定及细胞成分更新、保持正常的生理状态起着至关重要的作用．机体在生理和病理过程中都存在自噬,基础状态下的自噬对细胞具有保护和修复作用,而自噬过度激活会引起细胞的损伤及死亡．近年来,对自噬的研究主要集中于肿瘤细胞,而对正常细胞的自噬研究较少．血管内皮细胞作为人体中最活跃的细胞之一,其功能变化与心血管疾病的发生和发展有密切相关．本文对影响血管内皮细胞自噬的因素及其相关机制进行综述．