Angiopoietins differentially influence in vitro angiogenesis by endothelial cells of different origin

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

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Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis

AJP Cell Physiology ◽

10.1152/ajpcell.00223.2001 ◽

2002 ◽

Vol 282 (4) ◽

pp. C917-C925 ◽

Cited By ~ 39

Author(s):

Masako Yasuda ◽

Shunichi Shimizu ◽

Kyoko Ohhinata ◽

Shinji Naito ◽

Shogo Tokuyama ◽

...

Keyword(s):

Monoclonal Antibody ◽

Endothelial Cells ◽

Polymorphonuclear Leukocytes ◽

Vascular Endothelial Cell ◽

Collagen Gel ◽

Intercellular Adhesion Molecule ◽

Vascular Endothelial ◽

Endothelial Cell Cultures ◽

In Vitro Angiogenesis

Ets-1, which stimulates metalloproteinase gene transcription, has a key role in angiogenesis. We first examined whether activated polymorphonuclear leukocytes (PMNs) enhanced angiogenesis through the induction of Ets-1. Addition of activated PMNs to endothelial cells stimulated both in vitro angiogenesis in collagen gel and Ets-1 expression. Both angiogenesis and Ets-1 expression induced by PMNs were reduced by ets-1 antisense oligonucleotide, suggesting that Ets-1 is an important factor in PMN-induced angiogenesis. Although intercellular adhesion molecule (ICAM)-1 and E-selectin are involved in PMN-induced angiogenesis, the mechanisms underlying their roles in angiogenesis have yet to be elucidated. PMN-induced Ets-1 expression was reduced by a monoclonal antibody against ICAM-1 but not E-selectin despite the inhibition of PMN-induced angiogenesis by both antibodies. Moreover, the stimulation of angiogenesis by H2O2without PMNs was inhibited by a monoclonal antibody to E-selectin but not ICAM-1. These findings suggested that ICAM-1 in endothelial cells may act as a signaling receptor to induce Ets-1 expression, whereas E-selectin seems to function in the formation of tubelike structures in vascular endothelial cell cultures.

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Brassinosteroids inhibit in vitro angiogenesis in human endothelial cells

Steroids ◽

10.1016/j.steroids.2012.08.011 ◽

2012 ◽

Vol 77 (13) ◽

pp. 1502-1509 ◽

Cited By ~ 18

Author(s):

Lucie Rárová ◽

Stefan Zahler ◽

Johanna Liebl ◽

Vladimír Kryštof ◽

David Sedlák ◽

...

Keyword(s):

Endothelial Cells ◽

Human Endothelial Cells ◽

In Vitro Angiogenesis

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Three-Dimensional Simulation of In Vitro Angiogenesis: Effects of Extracellular Matrix Structure and Density

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19502 ◽

2010 ◽

Author(s):

Lowell Taylor Edgar ◽

James E. Guilkey ◽

Clayton J. Underwood ◽

Brenda Baggett ◽

Urs Utzinger ◽

...

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

Three Dimensional ◽

Vascular Endothelial ◽

Chemical Factors ◽

Dimensional Simulation ◽

Endothelial Growth Factor ◽

In Vitro Angiogenesis

The process of angiogenesis is regulated by both chemical and mechanical signaling. While the role of chemical factors such as vascular endothelial growth factor (VEGF) during angiogenesis has been extensively studied, the influence of the mechanostructural environment on new vessel generation has received significantly less attention. During angiogenesis, endothelial cells in the existing vasculature detach and migrate out into the surrounding extracellular matrix (ECM), forming tubular structures that eventually mature into new blood vessels. This process is modulated by the structure and composition of the ECM [1]. The ECM is then remodeled by endothelial cells in the elongating neovessel tip, resulting in matrix condensation and changes in fiber orientation [2]. The mechanism as to how angiogenic vasculature and the ECM influence each other is poorly understood.

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