Angiotensin II Type 2 Receptor Inhibits Vascular Endothelial Growth Factor–Induced Migration and In Vitro Tube Formation of Human Endothelial Cells

AbstractEndothelial cells (ECs), the primary component of the vasculature, play a crucial role in neovascularization. However, the number of endogenous ECs is inadequate for both experimental purposes and clinical applications. Porcine ovarian putative stem cells (poPSCs), although not pluripotent, are characterized by great plasticity. Therefore, this study aimed to investigate whether poPSCs have the potential to differentiate into cells of endothelial lineage. poPSCs were immunomagnetically isolated from postnatal pig ovaries based on the presence of SSEA-4 protein. Expression of mesenchymal stem cells (MSCs) markers after pre-culture, both at the level of mRNA: ITGB1, THY, and ENG and corresponding protein: CD29, CD90, and CD105 were significantly higher compared to the control ovarian cortex cells. To differentiate poPSCs into ECs, inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied. After 14 days, poPSC differentiation into ECs was confirmed by immunofluorescence staining for vascular endothelial cadherin (VECad) and vascular endothelial growth factor receptor-2 (VEGFR-2). Semi-quantitative WB analysis of these proteins confirmed their high abundance. Additionally, qRT-PCR showed that mRNA expression of corresponding marker genes: CDH5, KDR was significantly higher compared with undifferentiated poPSCs. Finally, EC functional status was confirmed by the migration test that revealed that they were capable of positive chemotaxis, while tube formation assay demonstrated their ability to develop capillary networks. In conclusion, our results provided evidence that poPSCs may constitute the MSC population in the ovary and confirmed that they might be a potential source of ECs for tissue engineering.

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Pro-Angiogenic Effects of Resveratrol in Brain Endothelial Cells: Nitric Oxide-Mediated Regulation of Vascular Endothelial Growth Factor and Metalloproteinases

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.2 ◽

2012 ◽

Vol 32 (5) ◽

pp. 884-895 ◽

Cited By ~ 43

Author(s):

Fabricio Simão ◽

Aline S Pagnussat ◽

Ji Hae Seo ◽

Deepti Navaratna ◽

Wendy Leung ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Signaling Pathways ◽

Tube Formation ◽

Mitogen Activated Protein Kinase ◽

Vascular Endothelial ◽

Cerebral Endothelial Cells ◽

Endothelial Growth Factor

Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of β-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.

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p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells

Oncogene ◽

10.1038/sj.onc.1201380 ◽

1997 ◽

Vol 15 (18) ◽

pp. 2169-2177 ◽

Cited By ~ 598

Author(s):

Simon Rousseau ◽

François Houle ◽

Jacques Landry ◽

Jacques Huot

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Cell Migration ◽

Growth Factor ◽

P38 Map Kinase ◽

Vascular Endothelial ◽

Human Endothelial Cells ◽

Actin Reorganization ◽

Kinase Activation ◽

Endothelial Growth Factor

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Transgenic Overexpression of Vascular Endothelial Growth Factor-B Isoforms by Endothelial Cells Potentiates Postnatal Vessel Growth In Vivo and In Vitro

Circulation Research ◽

10.1161/01.res.0000182631.33638.77 ◽

2005 ◽

Vol 97 (6) ◽

Cited By ~ 38

Author(s):

Arne W. Mould ◽

Sonia A. Greco ◽

Marian M. Cahill ◽

Ian D. Tonks ◽

Daniela Bellomo ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Vascular Endothelial ◽

Factor B ◽

Vessel Growth ◽

Endothelial Growth Factor

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Isolation and Characterisation of Lymphatic Endothelial Cells from Lung Tissues Affected by Lymphangioleiomyomatosis

10.21203/rs.3.rs-155950/v1 ◽

2021 ◽

Author(s):

Koichi Nishino ◽

Yasuhiro Yoshimatsu ◽

Tomoki Muramatsu ◽

Yasuhito Sekimoto ◽

Keiko Mitani ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Normal Lung ◽

Vascular Endothelial ◽

Lymphatic Endothelial Cells ◽

And Migration ◽

Endothelial Growth Factor ◽

Proliferation And Migration

Abstract Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.

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