血管内皮祖细胞与调控性细胞因子

血管内皮祖细胞是一群起源于骨髓，具有与来源于胚胎血岛细胞有着相似特征的单核细胞群，作为内皮细胞的前体细胞，是血管组织工程的良好种子细胞。研究对内皮祖细胞的动员、增殖和分化有着调控作用的多种细胞因子（如GM-CSF、G-CSF、VEGF、EPO等），对揭示生理和病理状态下血管新生和修复的机制有着重要意义。本文就内皮祖细胞与对其有着调控作用的细胞因子的关系作一综述。     

内皮祖细胞与血管介入治疗后再狭窄

介入治疗后再狭窄是影响经皮腔内血管成形术治疗疗效的主要原因,也是近年来研究的热点及难点之一.内皮祖细胞是一类能增生并分化成血管内皮细胞的前体细胞,参与体内内皮损伤后的修复和血管再生,有望在血管介入治疗后再狭窄的防治中起重要的作用,本文对内皮祖细胞的研究概况及其近年来在防治介入治疗后再狭窄的研究进展进行综述.     

血液透析患者内皮祖细胞数量和功能的改变

心血管并发症仍是长期透析患者的常见死亡原因,占透析患者死亡的40%.近年研究发现,存在于外周血中的内皮祖细胞(EPC)可参与出生后的血管新生和损伤血管的再内皮化过程,对内皮修复具有重要作用.本研究主要测定长期血液透析患者外周循环EPC的数量及功能变化,并探讨相关临床意义.     

SDF-1/CXCR7轴与肾脏缺血再灌注损伤

SDF-1/CXCR7轴是一对重要的趋化因子配体/受体,在胚胎发育、炎症反应、肿瘤形成及血管新生等生理病理过程中具有重要作用,近年的研究发现,SDF-1/CXCR7轴可促进内皮祖细胞及肾祖细胞生存、增殖、黏附以及跨内皮转移等,在肾脏缺血再灌注损伤的病理生理过程中发挥着重要作用.     

激素性股骨头坏死患者中两种内皮祖细胞功能的改变

目的 观察激素性股骨头坏死患者外周血中两种内皮祖细胞功能的改变,探讨其在激素导致的内皮功能失调中的作用.方法 选择33例激素性股骨头坏死患者和33例性别与年龄相匹配的健康人,从外周血中分离培养早期内皮祖细胞(EPCs)和内皮集落形成细胞(ECFCs),体外培养并检测其集落形成能力、CCK-8检测增殖能力、Transwell小室检测迁移能力、Matrigel胶检测成血管能力、酶联免疫吸附试验( ELISA)检测血管内皮生长因子(VEGF)和基质细胞衍生因子(SDF) 1细胞因子分泌水平.结果 激素性股骨头坏死患者中的两种内皮祖细胞集落形成能力均有所下降[早期EPC集落数:2.42±1.46比4.52±2.00(P＜0.05);ECFC集落数:0.62±0.55比1.12±0.82(P ＜0.05)],早期内皮祖细胞的迁移能力下降[63.8±11.7比152.3±12.4(P＜0.01)],分泌VEGF因子能力下降[(50.8±7.2) ng/L比(62.8±10.1)ng/L,P＜0.01],内皮集落形成细胞的增殖能力下降(P＜0.05),成血管能力下降[7.1±2.7比23.8±4.3(P＜0.01)].结论 激素性股骨头坏死患者中两种内皮祖细胞的功能在不同方面受损,表明其在激素导致的内皮功能失调中发挥不同作用.     

Lnk蛋白与内皮祖细胞在骨折愈合过程中作用的研究进展

Lnk蛋白是一种细胞衔接蛋白(adaptor protein),在细胞信号转导系统中起着重要的桥梁作用,其功能涉及到造血干细胞的分化、内皮细胞激活、细胞骨架调控等。在损伤的组织中,Lnk是造血干细胞自我更新和血管修复的较强负向调节因子。Lnk蛋白与内皮祖细胞介导血管发生,且在骨折愈合过程中发挥作用,本文将总结Lnk蛋白与内皮祖细胞在骨折愈合方面研究进展。     

重组腺病毒介导β半乳糖苷酶基因转染内皮祖细胞的实验研究

目的测定重组腺病毒介导β半乳糖苷酶基因对内皮祖细胞的转染率,为利用人类单纯疱疹病毒胸苷激酶（HSV-TK）基因转染内皮祖细胞治疗肺癌提供依据。方法将转染β半乳糖苷酶（LacZ）的重组腺病毒AD5F35（AD5F35LacZ）加入培养有内皮祖细胞的24孔板,转染内皮祖细胞。转染后用LacZ检测试剂盒染色,计算转染率。结果在光学显微镜下观察,蓝色细胞为AD5F35LacZ基因转染成功的内皮祖细胞。在不同感染复数MOI的前提下,腺病毒对内皮祖细胞的转染率是不同的,在一定的范围内,转染率随MOI的增大而增大,在MOI达到400时,转染率最大,为98．38％±1．25％。结论重组腺病毒可成功转染内皮祖细胞,转染率随MOI的增大而增大,当感染复数为400时转染率最大。     

血管内皮生长因子与治疗性血管生成研究进展

血管内皮生长因子(vascular endothelial growtll factor,VEGF)是内皮细胞特异的有丝分裂原,有促进内皮细胞增生、增强血管通透性、加速新血管形成的作用.血管生成是一个具有重要生理、病理意义的过程.在人体的创伤愈合、炎症反应、器官再生过程以及肿瘤生长转移、血管增生性疾病中,血管生成有重要作用.治疗性血管生成是指利用成血管诱导因子或内皮祖细胞,模拟体内血管生成机制,促进新生血管形成,改善侧支循环.本文就VEGF和治疗性血管生成研究进展做一综述.     

神经生长因子在血管生成中的研究进展

神经生长因子（NGF）是近年来治疗性血管生成研究领域的热点.NGF在神经的生长、发育、分化、存活等方面发挥着不可或缺的作用,同时NGF还可以促进内皮细胞、血管平滑肌细胞等的迁移、分化,甚至动员外周内皮祖细胞促进其活化,进而促进新生血管的形成。也可在与血管内皮生长因子的互相作用下促进内皮细胞的增生、迁移、分化,从而完成血管生成的过程.其在神经与血管的发生、发展中的重要作用为治疗外周动脉缺血性疾病打开了新的思路。     

内皮祖细胞的生物学特征及应用研究进展

成年人的外周血、骨髓和脐带血中存在一类能分化为成熟内皮细胞（endothelial cell,EC）的前体细胞,这种细胞参与新生血管的形成和血管再生,类似于胚胎期的成血管细胞,称为内皮祖细胞（endothelial progenitor cell,EPC）.它不仅参与胚胎时期的血管生成,而且在出生后微血管新生、损伤血管内皮修复和功能维持中仍有着重要的作用.     

Endothelial progenitor cells promote astrogliosis following spinal cord injury through Jagged1-dependent Notch signaling

Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.     

Die Rolle endothelialer Vorläuferzellen in der Sepsis

In sepsis and septic shock a series of immunological events are initiated that alter endothelial function in the macrocirculation and microcirculation. Endothelial swelling, deformation and apoptosis with detachment from the vasculature occur and endothelial cells (EC) appear in the circulation. Simultaneous to these pathological processes, reconstitution of the endothelial layer is initiated which can occur via migration and proliferation of surrounding mature ECs. However, terminally differentiated ECs have a low proliferative potential, hence their capacity to substitute damaged endothelium is limited. Therefore, adequate vascular repair requires additional support. Many studies have now convincingly demonstrated that vascular maintenance, repair, angiogenesis and neovascularization are partly mediated by recruitment of endothelial progenitor cells (EPCs) from the basal membrane. However, it seems that EPCs play a pivotal role not only in re-endothelialization after vascular damage, but also after severe inflammation. Recently, evidence was found that EPCs are increasingly mobilized during sepsis and that this mobilization is associated with clinical outcome. In septic patients the number of EPCs was significantly higher than in controls and was correlated with survival and the concentration of cytokines. In summary EPCs may exert an important function as an endogenous repair mechanism to maintain the integrity of the endothelial layer by replacing denuded parts of the microcirculation or by stimulation of EC proliferation. Therefore, EPC enumeration seems to be a valuable prognostic and diagnostic marker for the outcome in these patients and the induction of enhanced EPC mobilization a therapeutic option.     

Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells

OBJECTIVE: Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting. METHODS: Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion. RESULTS: Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients. CONCLUSIONS: Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.     

Molecular characterization of miniature porcine RANTES and its chemotactic effect on human mononuclear cells

To elucidate the potential role of porcine RANTES (Regulated upon Activation Normal T cells Expressed and Secreted) in xenograft rejection, we investigated its chemotactic activity for human mononuclear cells, as well as the effect of human cytokines on its expression in porcine endothelial cells. Porcine RANTES cDNA was successfully cloned from aortic endothelial cells of miniature pigs, and its protein expression was induced by transfection. Its deduced amino acid sequence was 83.5% identical to that of human RANTES. Porcine RANTES triggered transmigration of human mononuclear cells across the species barrier, and this chemotactic effect was suppressed by anti-RANTES neutralizing antibodies. The chemotactic effect of porcine RANTES was most prominent on human monocytes. Human tumor necrosis factor-alpha induced significant expression of porcine RANTES messenger RNA in endothelial cells; however both human interferon-gamma and interleukin-1beta failed. These results suggest that porcine RANTES can play an important role in xenotransplant rejection, through participating in the interaction between porcine endothelial cells and human monocytes.     

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs’ therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.     

毛细血管渗漏综合征中内皮祖细胞的作用

体外循环后毛细血管渗漏综合征的血管修复对该病的恢复起到至关重要的作用。外周血中存在着能分化为血管内皮细胞的内皮祖细胞，能够促进损伤血管修复和生后血管再生。血浆中的血管内皮生长因子（VEGF）、促红细胞生成素（EPO）等因子通过刺激血管内皮祖细胞的动员、迁移、黏附和分化，促进血管修复和再生。现对体外循环后血管内皮祖细胞的数量和功能情况及其与血浆相关因子的相互作用进行综述，旨在为毛细血管渗漏综合征的治疗和预防提供新的思路.     

Nitric oxide and endothelin in pathophysiological settings

The role of the endothelium, is now known to encompass the generation of many potent cytokines which impact endothelial cells, adjacent tissue such as smooth muscle cells, and distant sites in an autocrine, paracrine, and endocrine manner, respectively. This review addresses two of these cytokines, nitric oxide and endothelin, and describes how each effects the functions of endothelial cells, including regulation of platelet aggregation and coagulation, regulation of vasomotor tone, modulation of inflammation, and the regulation of cellular proliferation. The emphasis is on the increasingly recognized importance of the autocrine and paracrine mechanisms by which nitric oxide and endothelin act. In particular, autoinduction of endothelin is proposed as a central mechanism underlying endothelin's renowned effects. Additionally, specific nitric oxide/endothelin interactions are discussed by which each cytokine modulates the production and actions of the other. The net effect observed in a variety of physiological and pathophysiological settings, therefore, reflects a balance of these opposing functions.     

The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function

Recent evidence suggests that injury to the renal vasculature may play an important role in the pathogenesis of both early and chronic ischemic acute kidney injury (AKI). Established and new data support the suggestion that vascular injury, in particular, endothelial cell injury, participates in the extent and maintenance of AKI by pathways that are related to vascular tone. Early alterations in peritubular capillary blood flow during reperfusion has been documented and associated with loss of normal endothelial cell function, which can be replaced pharmacologically or with cell replacement interventions. Distorted peritubular capillary morphology is associated with loss of barrier function that may contribute to early alterations in vascular stasis. In addition, ischemia induces alterations in endothelial cells that may promote inflammation and procoagulant activity, thus contributing to vascular congestion. Reductions in microvasculature density may play a critical part in the progression of chronic kidney disease following initial recovery from ischemia/reperfusion-induced AKI. The exact nature of how capillary loss alters renal function and predisposes renal disease is thought to be due at least in part to hypoxia. Finally, the loss of endothelial cell function may represent an important therapeutic target in which nitric oxide, vascular trophic support, and/or endothelial progenitor cells may show potential importance in ameliorating the acute and/or chronic effects of ischemic AKI.