Cell behaviors and dynamics during angiogenesis

Betz, Charles; Lenard, Anna; Belting, Heinz‐Georg; Affolter, Markus

doi:10.1242/dev.135616

Cited by 188 publications

(163 citation statements)

References 115 publications

(138 reference statements)

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…Blood vessel development during embryogenesis is a multistep process that begins with primitive vessel formation from endothelial progenitor cells via vasculogenesis (Risau and Flamme, 1995;Drake and Fleming, 2000;Xu and Cleaver, 2011), and the subsequent formation of branched vessel networks by sprouting angiogenesis. Sprouting angiogenesis is initiated by endothelial cells that proliferate, extend processes, migrate into extravascular space, and finally connect, or anastomose, with another vessel (Betz et al, 2016;Blanco and Gerhardt, 2013;Larrivée et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

Nesmith

Chappell

et al. 2017

Development

View full text Add to dashboard Cite

Blood vessel formation is essential for vertebrate development and is primarily achieved by angiogenesis -endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation is poorly understood. Here, we show that vessel anastomosis is spatially regulated by Flt1 (VEGFR1), a VEGFA receptor that acts as a decoy receptor. In vivo, expanding vessel networks favor interactions with Flt1 mutant mouse endothelial cells. Live imaging in human endothelial cells in vitro revealed that stable connections are preceded by transient contacts from extending sprouts, suggesting sampling of potential target sites, and lowered Flt1 levels reduced transient contacts and increased VEGFA signaling. Endothelial cells at target sites with reduced Flt1 and/or elevated protrusive activity were more likely to form stable connections with incoming sprouts. Target cells with reduced membrane-localized Flt1 (mFlt1), but not soluble Flt1, recapitulated the bias towards stable connections, suggesting that relative mFlt1 expression spatially influences the selection of stable connections. Thus, sprout anastomosis parameters are regulated by VEGFA signaling, and stable connections are spatially regulated by endothelial cell-intrinsic modulation of mFlt1, suggesting new ways to manipulate vessel network formation.

show abstract

Section: Introductionmentioning

confidence: 99%

Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

Nesmith

Chappell

et al. 2017

Development

View full text Add to dashboard Cite

show abstract

“…Vascular networks are formed by the outgrowth of new blood vessels in a process called sprouting angiogenesis and their subsequent connection to another vessel or sprout by anastomosis. At the cellular level, sprouting angiogenesis and anastomosis are characterized by a series of dynamic behaviors, which are tightly coordinated (reviewed by Betz et al, 2016;Wacker and Gerhardt, 2011). In response to pro-angiogenic signals, endothelial cells (ECs) are activated.…”

Section: Introductionmentioning

confidence: 99%

“…The cellular mechanisms that underlie blood vessel morphogenesis have been analyzed in detail by in vivo time-lapse microscopy in the zebrafish embryo (reviewed by Betz et al, 2016;Schuermann et al, 2014). During the formation of segmental arteries (SeAs), two or more cells emigrate from the dorsal aorta (DA) and form an angiogenic sprout.…”

Section: Introductionmentioning

confidence: 99%

Distinct and redundant functions of Esam and VE-cadherin during vascular morphogenesis

2017

Self Cite

View full text Add to dashboard Cite

The cardiovascular system forms during early embryogenesis and adapts to embryonic growth by sprouting angiogenesis and vascular remodeling. These processes require fine-tuning of cell-cell adhesion to maintain and re-establish endothelial contacts, while allowing cell motility. We have compared the contribution of two endothelial cellspecific adhesion proteins, VE-cadherin (VE-cad/Cdh5) and Esama (endothelial cell-selective adhesion molecule a), during angiogenic sprouting and blood vessel fusion (anastomosis) in the zebrafish embryo by genetic analyses. Different combinations of mutant alleles can be placed into a phenotypic series with increasing defects in filopodial contact formation. Contact formation in esama mutants appears similar to wild type, whereas esama −/− ; ve-cad +/− and ve-cad single mutants exhibit intermediate phenotypes. The lack of both proteins interrupts filopodial interaction completely. Furthermore, double mutants do not form a stable endothelial monolayer, and display intrajunctional gaps, dislocalization of Zo-1 and defects in apical-basal polarization. In summary, VE-cadherin and Esama have distinct and redundant functions during blood vessel morphogenesis, and both adhesion proteins are central to endothelial cell recognition during anastomosis.

show abstract

“…Angiogenesis is the formation of new blood vessels from pre-existing vessels, and is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation [1,4]. When quiescent endothelial cells are activated by various stimuli, activated endothelial cells degrade extracellular matrix, proliferate, and migrate to the site of stimuli.…”

Section: Introductionmentioning

confidence: 99%

“…Angiogenesis is involved in embryonic vasculature formation and is a central process in cancer progression, which means that tumor growth can be effectively inhibited by anti-angiogenic therapy [1,5]. Conversely, angiogenesis is also an important physiological process for promoting revascularization to overcome tissue ischemia.…”

Section: Introductionmentioning

confidence: 99%

Cilostazol Promotes the Migration of Brain Microvascular Endothelial Cells

Lee¹,

Park²,

Shin³

2016

Journal of Life Science

View full text Add to dashboard Cite

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein β (C/EBPβ) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

show abstract

Cell behaviors and dynamics during angiogenesis

Cited by 188 publications

References 115 publications

Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

Distinct and redundant functions of Esam and VE-cadherin during vascular morphogenesis

Cilostazol Promotes the Migration of Brain Microvascular Endothelial Cells

Contact Info

Product

Resources

About