Comparison of Anti-Angiogenic Activities of Thalidomide and Lenalidomide In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3959-3959 ◽  
Author(s):  
Ling-Hua Zhang ◽  
Ling Lu ◽  
Lei Wu ◽  
Keith Dredge ◽  
J. Blake Bartlett ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Endothelial Cell Migration ◽  
Scaffolding Protein ◽  
Component Part ◽  
Migration Assays

Abstract Inhibition of angiogenesis is currently perceived as one of the promising strategies in the cancer therapy. Thalidomide (Thalomid®) and its Immunomodulatory Drug (IMiD®) analogs have entered into clinical trials for the treatment of various types of cancers. Lenalidomide (Revlimid®, CC-5013) is currently being assessed in oncology clinical trials worldwide. In this study we have compared the anti-angiogenic mechanisms of thalidomide and lenalidomide in a variety of experimental systems representing distinct events of the angiogenic process. Endothelial cell (EC) proliferation is stimulated by growth factors. Neither thalidomide nor lenalidomide have an appreciable inhibitory effect on growth factor-induced proliferation of human umbilical vein endothelial cells (HUVEC). In both the HUVEC and B16-F10 mouse melanoma tube formation assays, lenalidomide appears to be at least 10-fold more potent than thalidomide, the latter indicating that effects extend to vessels lined by tumor cells. However, in endothelial cell migration assays, thalidomide is more active than lenalidomide; in both the HUVEC and B16-F10 monolayer scratch migration assays, thalidomide is clearly more potent than lenalidomide in preventing the migration of cells into the wounded/scratched region. In assays of HUVEC migration towards specific angiogenic factors, such as VEGF, bFGF, and TNF-α, thalidomide is also more potent than lenalidomide. Interestingly, assays where the whole physiological process of angiogenesis can be studied show differential sensitivities. Lenalidomide is more potent in the rat aorta assay, whereas thalidomide is more potent in the human umbilical explant assay. Mechanistic studies on signal transduction events triggered by VEGF show that both thalidomide and lenalidomide partially inhibit Akt phosphorylation in VEGF-induced HUVEC. Furthermore, inhibitory effects on the phosphorylation of Gab1, a scaffolding protein upstream of Akt activation, have been observed. In summary, our data indicate that both thalidomide and lenalidomide interfere with key events in the angiogenic process and that they can be differentiated qualitatively depending on which component part is studied.

Abstract 1461: BLADE Is A Novel Membrane Protein That Regulates Endothelial Apoptosis and Consequently Angiogenesis Both In Vitro and In Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Koji Ikeda ◽  
Ritsuko Nakano ◽  
Thomas Quertermous ◽  
Hiroaki Matsubara
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Membrane Protein ◽  
Umbilical Vein ◽  
Hepatoma Cell ◽  
Endothelial Cell Migration ◽  
Late Time ◽  
Endothelial Apoptosis

Endothelial apoptosis is a pivotal process for angiogenesis during embryogenesis as well as postnatal. Here, we identified a novel gene, termed BLADE, that regulates endothelial apoptosis and consequently angiogenesis. BLADE was highly expressed in a variety of human cultured endothelial cells such as endothelial cells from umbilical vein (HUVEC), aorta, coronary artery and microvessels while no expression was observed in non-endothelial cells including HeLa cell, hepatoma cell and vascular smooth muscle cells. Furthermore, BLADE was expressed predominantly in blood vessels during embryogenesis, suggesting its role in angiogenesis. Amino acid sequence analysis revealed that BLADE was a novel membrane protein with no conserved domain reported before. BLADE expression was altered by treatment with VEGF, TNF-alpha and TGF-beta in HUVEC. Knockdown of BLADE in HUVEC using short interference RNA resulted in significant reduction of endothelial apoptosis. In contrast, BLADE knockdown affected neither endothelial cell migration nor proliferation. Among factors associated with apoptosis, Bcl-2 expression was drastically increased in HUVEC by BLADE-knockdown. Further analysis revealed that this increase of Bcl-2 is due to reduced ubiquitination and less subsequent degradation of Bcl-2. Inhibition of Bcl-2 completely abolished the anti-apoptotic effect of BLADE-knockdown. In vitro tube-formation of HUVEC on Matrigel was reduced concomitantly with reduced apoptosis by BLADE-knockdown at early time (12h). Nevertheless, significantly more tubes were preserved at late time (96h) by BLADE-knockdown. Moreover, in vivo angiogenesis assessed by Matrigel-plug was dramatically enhanced by BLADE-knockdown. Taken together, BLADE is a novel factor regulating endothelial apoptosis as well as angiogenesis both in vitro and in vivo. Detailed analysis of BLADE will provide new insights in the regulation of endothelial apoptosis, and in the molecular link between endothelial apoptosis and angiogenesis. Because BLADE is highly preferentially expressed in endothelial cells, inhibition of BLADE might be an ideal approach to enhance endothelial cell survival and angiogenesis without affecting the survival of other type of cells.

Signaling and regulation of endothelial cell survival by angiopoietin-2

2006 ◽  
Vol 291 (4) ◽  
pp. H1635-H1645 ◽  
Author(s):  
Rania Harfouche ◽  
Sabah N. A. Hussain
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Survival ◽  
Umbilical Vein ◽  
Biological Effects ◽  
Pi3 Kinase ◽  
Endothelial Cell Migration ◽  
Endothelial Cell Survival ◽  
Induced Apoptosis

Angiopoietins are ligands for endothelial cell-specific Tie-2 receptors. Whereas angiopoietin-1 (Ang-1) activates these receptors and promotes cell survival, migration, and sprouting, little information is available regarding how Ang-2 influences these cells. In this study, we evaluated signaling pathways and biological effects of physiological concentrations of Ang-2 in cultured human umbilical vein endothelial cells. Ang-2 at 150 and 300 ng/ml elicited a transient (reaching peak values within 15 min of exposure) increase in the phosphorylation of Tie-2 receptors, protein kinase B (Akt), ERK1/2, and p38 members of the mitogen-activated protein kinases. However, unlike Ang-1, Ang-2 significantly inhibited JNK/SAPK phosphorylation. When vascular endothelial growth factor (VEGF) was present along with Ang-2, ERK1/2 phosphorylation was inhibited, whereas augmentation of Ang-1-induced ERK1/2 phosphorylation was triggered by VEGF. Ang-2 treatment had no effect on cell migration and in vitro wound healing but significantly attenuated serum deprivation-induced apoptosis and promoted survival. These effects were completely reversed by phosphatidylinositol 3 (PI3)-kinase and ERK1/2 inhibitors but were augmented by an inhibitor of the p38 pathway. These results suggest that Ang-2 promotes endothelial cell survival through the ERK1/2 and PI3-kinase pathways and that this angiopoietin is not a strong promoter of endothelial cell migration. We also conclude that the nature of interactions in terms of ERK1/2 activation between Ang-2 and VEGF is different from that of Ang-1 and VEGF.

In vitro inhibitory effect of crab shell extract on human umbilical vein endothelial cell

2014 ◽  
Vol 51 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Pegah Mirzapur ◽  
Zahra Rashidi ◽  
Leila Rezakhani ◽  
Mozafar Khazaei
Keyword(s):  
Endothelial Cell ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Crab Shell ◽  
Human Umbilical Vein

scholarly journals The effect of RhoA on human umbilical vein endothelial cell migration and angiogenesis in vitro

2006 ◽  
Author(s):  
Liangping Zhao ◽  
Gang Xu ◽  
Jianfeng Zhou ◽  
Hui Xing ◽  
Shixuan Wang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Endothelial Cell Migration ◽  
Human Umbilical Vein

Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration

2002 ◽  
Vol 282 (5) ◽  
pp. C1181-C1190 ◽  
Author(s):  
Gaoyuan Cao ◽  
Christopher D. O'Brien ◽  
Zhao Zhou ◽  
Samuel M. Sanders ◽  
Jordan N. Greenbaum ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tumor Angiogenesis ◽  
Umbilical Vein ◽  
Severe Combined Immunodeficiency ◽  
Human Tumor ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Simultaneous Treatment

Platelet endothelial cell adhesion molecule (PECAM)-1 has been implicated in angiogenesis, but a number of issues remain unsettled, including the independent involvement of human PECAM-1 (huPECAM-1) in tumor angiogenesis and the mechanisms of its participation in vessel formation. We report for tumors grown in human skin transplanted on severe combined immunodeficiency mice that antibodies against huPECAM-1 (without simultaneous treatment with anti-VE-cadherin antibody) decreased the density of human, but not murine, vessels associated with the tumors. Anti-huPECAM-1 antibody also inhibited tube formation by human umbilical vein endothelial cells (HUVEC) and the migration of HUVEC through Matrigel-coated filters or during the repair of wounded cell monolayers. The involvement of huPECAM-1 in these processes was confirmed by the finding that expression of huPECAM-1 in cellular transfectants induced tube formation and enhanced cell motility. These data provide evidence of a role for PECAM-1 in human tumor angiogenesis (independent of VE-cadherin) and suggest that during angiogenesis PECAM-1 participates in adhesive and/or signaling phenomena required for the motility of endothelial cells and/or their subsequent organization into vascular tubes.

scholarly journals Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5423-5433 ◽  
Author(s):  
Baofeng Zhao ◽  
Changzoon Chun ◽  
Zhong Liu ◽  
Mark A. Horswill ◽  
Kallal Pramanik ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract Our previous work has shown that axon guidance gene family Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro. To investigate NogoB-NgBR function in vivo, we cloned the zebrafish ortholog of both genes and studied loss of function in vivo using morpholino antisense technology. Zebrafish ortholog of Nogo-B is expressed in somite while expression of zebrafish NgBR is localized in intersomitic vessel (ISV) and axial dorsal aorta during embryonic development. NgBR or Nogo-B knockdown embryos show defects in ISV sprouting in the zebrafish trunk. Mechanistically, we found that NgBR knockdown not only abolished its ligand Nogo-B–stimulated endothelial cell migration but also reduced the vascular endothelial growth factor (VEGF)–stimulated phosphorylation of Akt and vascular endothelial growth factor–induced chemotaxis and morphogenesis of human umbilical vein endothelial cells. Further, constitutively activated Akt (myristoylated [myr]Akt) or human NgBR can rescue the NgBR knockdown umbilical vein endothelial cell migration defects in vitro or NgBR morpholino-caused ISV defects in vivo. These data place Akt at the downstream of NgBR in both Nogo-B– and VEGF-coordinated sprouting of ISVs. In summary, this study identifies the in vivo functional role for Nogo-B and its receptor (NgBR) in angiogenesis in zebrafish.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

Abstract 116: Arterial Endothelial Cell Has Stronger Angiogenic Potential Compared To Venous Endothelial Cell Through Up-regulation Of Endogenous FGF2 And FGF5 Expression In 3D Microfluidic System

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ha-Rim Seo ◽  
Hyo Eun Jeong ◽  
Hyung Joon Joo ◽  
Seung-Cheol Choi ◽  
Jong-Ho Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Assay System ◽  
Vascular Density ◽  
Angiogenic Potential ◽  
Angiogenesis Assay

Background: Human body contains many kinds of different type of endothelial cells (EC). However, cellular difference of their angiogenic potential has been hardly understood. We compared in vitro angiogenic potential between arterial EC and venous EC and investigated its underlying molecular mechanisms. Method: Used human aortic endothelial cells (HAEC) which was indicated from arterial EC and human umbilical vein endothelial cells (HUVEC) indicated from venous EC. To explore angiogenic potential in detail, we adopted a novel 3D microfluidic angiogenesis assay system, which closely mimic in vivo angiogenesis. Results: In 3D microfluidic angiogenesis assay system, HAEC demonstrated stronger angiogenic potential compared to HUVEC. HAEC maintained its profound angiogenic property under different biophysical conditions. In mRNA microarray sorted on up- regulated or down-regulated genes, HAEC demonstrated significantly higher expression of gastrulation brain homeobox 2 (GBX2), fibroblast grow factor 2 (FGF2), FGF5 and collagen 8a1. Angiogenesis-related protein assay revealed that HAEC has higher secretion of endogenous FGF2 than HUVEC. HAEC has only up-regulated FGF2 and FGF5 in this part of FGF family. Furthermore, FGF5 expression under vascular endothelial growth factor-A (VEGF-A) stimulation was higher in HAEC compared to HUVEC although VEGF-A augmented FGF5 expression in both HAEC and HUVEC. Those data suggested that FGF5 expression in both HAEC and HUVEC is partially dependent to VEGF-A stimulate. HUVEC and HAEC reduced vascular density after FGF2 and FGF5 siRNA treat. Conclusion: HAEC has stronger angiogenic potential than HUVEC through up-regulation of endogenous FGF2 and FGF5 expression

A comparative assessment of e-cigarette aerosols and cigarette smoke on in vitro endothelial cell migration

2017 ◽  
Vol 280 ◽  
pp. S235-S236
Author(s):  
Mark Taylor ◽  
Tomasz Jaunky ◽  
Katherine Hewitt ◽  
Frazer Lowe ◽  
Ian Fearon ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Cigarette Smoke ◽  
Comparative Assessment ◽  
Endothelial Cell Migration
Sign in / Sign up

Export Citation Format

Share Document