Angiopoietin 1 Is Mitogenic for Cultured Endothelial Cells

Kanda, Shigeru; Miyata, Yasuyoshi; Mochizuki, Yoshinari; Matsuyama, Tomohiro; Kanetake, Hiroshi

doi:10.1158/0008-5472.can-05-0522

Cited by 74 publications

(57 citation statements)

References 47 publications

(60 reference statements)

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“…Although the mitogenic activity of ang-1 on endothelial cells has been proven (25), In our experiment, AAV-mediated ang-1 expression did not increase capillary density in ischemic hearts, while AAV-mediated VEGF expression increased the densities of both CAP and α-SMA positive vessels. Expression of ang-1 did increase the number of α-SMA positive vessels; however, co-expression of ang-1 with VEGF did not increase the vessel density above the levels of VEGF.…”

Section: Discussioncontrasting

confidence: 68%

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

Takagawa

Huang

et al. 2009

International Journal of Cardiology

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Vascular endothelial growth factor (VEGF) is a key angiogenic factor and has been used experimentally for induction of neovasculature in ischemic myocardium. However, blood vessels induced by VEGF are immature. Angiopoietin-1 (ang-1) has the ability to recruit and sustain periendothelial support cells and promote vascular maturation. Thus, co-expression of the two may yield a better result than expression of either one alone. Two adeno-associated viral vectors (AAV), CMVVEGF and CMVang-1 with the CMV promoter driving VEGF or ang-1 gene expression, respectively, were injected into ischemic mouse hearts individually or together in different ratios. The results show that co-injected groups had more capillaries than the CMVang-1 group and similar densities of capillaries and α-actin positive vessels as the CMVVEGF group. Neovasculature induced by CMVVEGF was leaky. In contrast, neovasculature in CMVang-1-injected or CMVVEGF and CMVang-1 co-injected hearts was less leaky than that in CMVVEGF-injected hearts. The group that received CMVang-1 and CMVVEGF in a 1:1 ratio had the smallest infarct size and best cardiac function and regional wall movement among all the groups. We conclude that ang-1 and VEGF can compensate for each others' shortcomings and yield a better therapeutic effect by acting together.

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Section: Discussioncontrasting

confidence: 68%

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

Takagawa

Huang

et al. 2009

International Journal of Cardiology

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“…The data describe above data have two implications: First, they provide the basis for the construction of a novel targeting tools for Tie2 starting from BbcA2 as lead compound. This receptor and its ligands are involved in disparate activities and its pharmacological modulation may have an impact in wide array of clinical settings, ranging from angiogenesis to inflammation to cancer [6] . BbcA2 is a small peptide activator of the Tie2.…”

Section: Discussionmentioning

confidence: 99%

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

Graziano

Marchiò

Bussolino

et al. 2013

Biochemical and Biophysical Research Communications

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Neurexin (NRXN) and Neuroligin (NLGN) are trans-synaptic proteins involved in vascular biology. NRXN is encoded in long () and short () isoforms. We have shown that NRXNmodulates blood vessel development in synergy with VEGFA and associates with NLGN. On the other hand NRXN is also expressed in blood vessels but does not interact with NLGN or act in synergy with VEGFA, thus demonstrating a differential role. To find clues into the vascular functions of NRXN, we chose a 7 aa motif that is part of its extracellular region and was formerly selected through a proteomic search for interactors of the vascular receptor Tie2. Next we a) synthetized and modeled such peptide in order to determine its biological activity towards Tie2 in in vitro and in vivo angiogenesis assays and b) evaluated if NRXN and Tie2 physically associate in situ during vascular development. We used biochemical and cellular assays to prove that the synthetic NRXN peptide a) modulates the angiogenic phenotype of cultured endothelial cells and angiogenesis in vivo and b) efficiently stimulates Tie2 phosphorylation and downstream mediators in endothelial cells. Moreover, we show that NRXN and Tie2 can be reciprocally immunoprecipated from chicken blood vessels at late stages of vascular development. These data have a double significance, i.e. provide a novel tool to modulate Tie2 and further suggest the involvement of the NRXN family of synaptic protein in the vascular system through their interaction with a fundamental vascular player.

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“…Due to Tie-2 and Ang-1 being involved in vessel stabilization, these factors are not expressed in vast quantities until the latter stages of angiogenesis. Ang-1 induced activation of Tie-2 results in the remodeling and stabilization of vessels by inducing endothelial cells to associate with their matrix and recruit pericytes to support the vessels (Kanda et al 2005). It has been found in one study that Ang-1 and Tie-2 immunoreactivity were present in choroidal neovascular cells from AMD patients (Otani, Takagi et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Changes in growth factor expression in normal aging of the rat retina

Smith

Steinle

2007

Experimental Eye Research

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Although much is known about the growth factor changes in ocular tissues during various diseases, little is known about normal aging of the retina. In order to further understand normal aging in the retina, we characterized age-related changes of growth factor expression in three different ages of rat retina. Real time PCR and protein analysis was conducted to investigate steady state mRNA expression and protein levels of VEGF, VEGFR2, PEDF, Ang-1, Tie-2, EphB4 and ephrinB2 in the retina of 8, 22, and 32 month old Brown Norway X Fischer 344 F1 hybrid rats. An increase of VEGF protein levels was found at 32 months compared to 8 and 22 months of age. VEGFR2 protein was found to be increased at 22 and 32 months compared to 8 months. PEDF protein levels were reduced at 22 and 32 months. Tie-2 levels were found to be significantly decreased by 32 months compared to 8 months of age, while ephrinB2 was found to be significantly lower at both 22 and 32 months compared to 8 months of age. The increases found in VEGF and its receptor VEGFR2, with the simultaneous decrease of PEDF protein levels, may stimulate an environment that is well suited for neovascularization in the normal aging retina. Overall, these results suggest that normal aging produces substantial changes in gene expression and protein levels.

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Angiopoietin 1 Is Mitogenic for Cultured Endothelial Cells

Abstract: The angiopoietin (Ang)/Tie2 system is implicated in blood vessel formation and maturation. However, the mitogenic effects of angiopoietins remain to be elucidated. Here, we show that Ang1 is mitogenic for cultured endothelial cells.

Cited by 74 publications

References 47 publications

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

Changes in growth factor expression in normal aging of the rat retina

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