Inhibition of angiogenic key features in vitro: the alkaloid narciclasine blocks proliferation, migration, and tube formation of primary human endothelial cells

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
J Bräutigam ◽  
DL Nguyen ◽  
E Heiss ◽  
I Bischoff ◽  
R Fürst
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Human Endothelial Cells ◽  
Key Features

scholarly journals Toxic Damage Increases Angiogenesis and Metastasis in Fibrotic Livers via PECAM-1

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Esther Raskopf ◽  
Maria Angeles Gonzalez Carmona ◽  
Christina Jay Van Cayzeele ◽  
Christian Strassburg ◽  
Tilman Sauerbruch ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Liver Damage ◽  
Tube Formation ◽  
Ethanol Exposure ◽  
Human Endothelial Cells ◽  
Cell Functions ◽  
Promising Tool ◽  
Toxic Damage

Excessive ethanol consumption is one of the main causes of liver fibrosis. However, direct effects of ethanol exposure on endothelial cells and their contribution to fibrogenesis and metastasis were not investigated. Therefore we analysed whether ethanol directly affects endothelial cells and if this plays a role during fibrogenesis and metastasis in the liver. Murine and human endothelial cells were exposed to ethanol for up to 72 hours.In vitro, effects on VEGF, HIF-1alpha, PECAM-1, and endothelial cell functions were analysed.In vivo, effects of continuous liver damage on blood vessel formation and metastasis were analysed by PECAM-1 immunohistochemistry. Ethanol increased HIF-1alpha and VEGF levels in murine and human endothelial cells. This resulted in enhanced intracellular signal transduction, and PECAM-1 expression as well as tube formation and wound healing.In vivo, toxic liver damage increased angiogenesis during fibrogenesis. Metastasis was also enhanced in fibrotic livers and located to PECAM-1 positive blood vessels compared to nonfibrotic mice. In conclusion, ethanol had strong effects on endothelial cells, which—at least in part—led to a profibrotic and prometastatic environment mediated by PECAM-1. Blockade of increased PECAM-1 expression could be a promising tool to inhibit fibrogenesis and metastasis in the liver.

scholarly journals mTORC1-Mediated Angiogenesis is Required for the Development of Rosacea

2021 ◽  
Vol 9 ◽  
Author(s):  
Qinqin Peng ◽  
Ke Sha ◽  
Yingzi Liu ◽  
Mengting Chen ◽  
San Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Model ◽  
Skin Lesions ◽  
Tube Formation ◽  
Human Endothelial Cells ◽  
Lesional Skin ◽  
Mtorc1 Signaling ◽  
Inhibition Of Angiogenesis

Although multiple evidences suggest that angiogenesis is associated with the pathophysiology of rosacea, its role is still in debate. Here, we showed that angiogenesis was enhanced in skin lesions of both rosacea patients and LL37-induced rosacea-like mice. Inhibition of angiogenesis alleviated LL37-induced rosacea-like features in mice. Mechanistically, we showed that mTORC1 was activated in the endothelial cells of the lesional skin from rosacea patients and LL37-induced rosacea-like mouse model. Inhibition of mTORC1 decreased angiogenesis and blocked the development of rosacea in mice. On the contrary, hyperactivation of mTORC1 increased angiogenesis and exacerbated rosacea-like phenotypes. Our in vitro results further demonstrated that inhibition of mTORC1 signaling significantly declined LL37-induced tube formation of human endothelial cells. Taken together, our findings revealed that mTORC1-mediated angiogenesis responding to LL37 might be essential for the development of rosacea and targeting angiogenesis might be a novel potential therapy.

Hydroxysafflor yellow A promotes angiogenesis in rat brain microvascular endothelial cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R) through SIRT1-HIF-1α-VEGFA signaling pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Juxuan Ruan ◽  
Lei Wang ◽  
Jiheng Dai ◽  
Jing Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Hydroxysafflor Yellow A ◽  
Microvascular Endothelial

Objective: Angiogenesis led by brain microvascular endothelial cells (BMECs) contributes to the remission of brain injury after brain ischemia reperfusion. In this study, we investigated the effects of hydroxysafflor yellow A(HSYA) on angiogenesis of BMECs injured by OGD/R via SIRT1-HIF-1α-VEGFA signaling pathway. Methods: The OGD/R model of BMECs was established in vitro by OGD for 2h and reoxygenation for 24h. At first, the concentrations of vascular endothelial growth factor (VEGF), Angiopoietin (ang) and platelet-derived growth factor (PDGF) in supernatant were detected by ELISA, and the proteins expression of VEGFA, Ang-2 and PDGFB in BMECs were tested by western blot; the proliferation, adhesion, migration (scratch healing and transwell) and tube formation experiment of BMECs; the expression of CD31 and CD34 were tested by immunofluorescence staining. The levels of sirtuin1(SIRT1), hypoxia-inducible factor-1α (HIF-1α), VEGFA mRNA and protein were tested. Results: HSYA up-regulated the levels of VEGF, Ang and PDGF in the supernatant of BMECs under OGD/R, and the protein expression of VEGFA, Ang-2 and PDGFB were increased; HSYA could significantly alleviate the decrease of cell proliferation, adhesion, migration and tube formation ability of BMECs during OGD/R; HSYA enhanced the fluorescence intensity of CD31 and CD34 of BMECs during OGD/R; HSYA remarkably up-regulated the expression of SIRT1, HIF-1α, VEGFA mRNA and protein after OGD/R, and these increase decreased after SIRT1 was inhibited. Conclusion: SIRT1-HIF-1α-VEGFA signaling pathway is involved in HSYA improves angiogenesis of BMECs injured by OGD/R.

Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation

2015 ◽  
Vol 113 (06) ◽  
pp. 1312-1322 ◽  
Author(s):  
Sofia Nordling ◽  
Jaan Hong ◽  
Karin Fromell ◽  
Fredrik Edin ◽  
Johan Brännström ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Thrombus Formation ◽  
Innate Immune ◽  
Human Endothelial Cells ◽  
Coagulation Activation ◽  
Ischaemia Reperfusion Injury ◽  
Novel Approach ◽  
One Step ◽  
Chamber Model

SummaryIschaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vasculature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothelial cells and collagen of the basement membrane ensures to protect the endothelium against IRI in thrombotic disorders and in transplantation.

Centrifugal enhancement of Kaposi's sarcoma-associated virus infection of human endothelial cells in vitro

2008 ◽  
Vol 154 (1-2) ◽  
pp. 160-166 ◽  
Author(s):  
Seung-Min Yoo ◽  
Ae-Kyung Ahn ◽  
Taegun Seo ◽  
Hyo Bong Hong ◽  
Myung-Ae Chung ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Virus Infection ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Human Endothelial Cells

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Po-Ku Chen ◽  
Bi-Ing Chang ◽  
Meng-Chen Sung ◽  
Chung-Sheng Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Egf Receptor ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
A Cell ◽  
Lewis Y ◽  
Tm Domain

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

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