Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1

Ec, Watson; Whitehead, Lachlan; Adams, Ralf H.; Dewson, Grant; Coultas, Leigh

doi:10.1038/cdd.2016.20

Cited by 28 publications

(32 citation statements)

References 47 publications

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“…Consistent with previous reports (Simonavicius et al, 2012;Watson et al, 2016), we found that apoptosis was predominantly located around arteries at postnatal day (P) 6, with a limited amount around the veins and almost none in the sprouting region (Fig. 1A,B).…”

Section: Resultssupporting

confidence: 92%

“…Our data argue against a role for apoptosis promoting vessel regression during angiogenesis. Furthermore, mice with EC-specific loss of the pro-survival protein MCL1 exhibited a far greater increase in apoptosis than that reported for mice lacking non-canonical Wnt, but did not show an increase in vessel regression (Watson et al, 2016). These findings would argue against a role for apoptosis in promoting vessel regression, even when ectopically activated.…”

Section: Discussionmentioning

confidence: 73%

“…6A,B). Apoptotic vessel regression was completely absent or nearly absent in three out of five mutants, whereas one animal showed normal hyaloid apoptosis, possibly due to cre inefficiency, which we occasionally observe with Tie2-cre (Watson et al, 2016). At 4 weeks of age, hyaloid vessels had fully regressed in control mice.…”

Section: Hyaloid Vessel Regression In Bakmentioning

confidence: 64%

“…Although loss of the BH3-only protein BIM reduces EC apoptosis in the angiogenic retina (Koenig et al, 2014), it does not prevent EC apoptosis under all circumstances (Koenig et al, 2014;Watson et al, 2016), probably due to compensatory apoptosis initiation by other BH3-only proteins, as occurs in other cell types (Coultas et al, 2005). In order to overcome BH3-only protein redundancy and study angiogenesis in the complete absence of apoptosis, we generated mice in which ECs lacked both of the apoptosis effector proteins BAK and BAX.…”

Section: Resultsmentioning

confidence: 99%

“…Apoptosis is responsible for tissue remodelling and regulating cell number in a range of tissues and organs during development (Fuchs and Steller, 2011) and much of this occurs through the intrinsic pathway, as shown by the combined loss of BAK and BAX (Lindsten et al, 2000). The intrinsic apoptosis pathway is essential for survival regulation in ECs: loss of the BH3-only protein BIM prevents EC apoptosis during normal and tumour-associated angiogenesis in vivo (Koenig et al, 2014;Naik et al, 2011;Wang et al, 2011), whereas EC-specific loss of the pro-survival BCL2 family protein MCL1 leads to ectopic EC apoptosis during angiogenesis in vivo (Watson et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel regression during retinal angiogenesis

Koenig

Grant

et al. 2016

Development

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The growth of hierarchical blood vessel networks occurs by angiogenesis. During this process, new vessel growth is accompanied by the removal of redundant vessel segments by selective vessel regression ('pruning') and a reduction in endothelial cell (EC) density in order to establish an efficient, hierarchical network. EC apoptosis has long been recognised for its association with angiogenesis, but its contribution to this process has remained unclear. We generated mice in which EC apoptosis was blocked by tissue-specific deletion of the apoptosis effector proteins BAK and BAX. Using the retina as a model, we found that apoptosis made a minor contribution to the efficiency of capillary regression around arteries where apoptosis was most concentrated, but was otherwise dispensable for vessel pruning. Instead, apoptosis was necessary for the removal of non-perfused vessel segments and the reduction in EC density that occurs during vessel maturation. In the absence of apoptosis, increased EC density resulted in an increase in the diameter of capillaries, but not arteries or veins. Our findings show that apoptosis does not influence the number of vessels generated during angiogenesis. Rather it removes non-perfused vessel segments and regulates EC number during vessel maturation, which has vessel-specific consequences for vessel diameter.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 73%

Section: Hyaloid Vessel Regression In Bakmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel regression during retinal angiogenesis

Koenig

Grant

et al. 2016

Development

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Extracellular vesicles rich in HAX1 promote angiogenesis by modulating ITGB6 translation

You

Pan

et al. 2022

J of Extracellular Vesicle

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Tumour‐associated angiogenesis plays a critical role in metastasis, the main cause of malignancy‐related death. Extracellular vesicles (EVs) can regulate angiogenesis to participate in tumour metastasis. Our previous study showed that EVs rich in HAX1 are associated with in metastasis of nasopharyngeal carcinoma (NPC). However, the mechanism by which HAX1 of EVs promotes metastasis and angiogenesis is unclear. In this study, we demonstrated that EVs rich in HAX1 promote angiogenesis phenotype by activating the FAK pathway in endothelial cells (ECs) by increasing expression level of ITGB6. The expression level of HAX1 is markedly correlated with microvessel density (MVDs) in NPC and head and neck cancers based on an analysis of IHC. In addition to a series of in vitro cellular analyses, in vivo models revealed that HAX1 was correlated with migration and blood vessel formation of ECs, and metastasis of NPC. Using ribosome profiling, we found that HAX1 regulates the FAK pathway to influence microvessel formation and promote NPC metastasis by enhancing the translation efficiency of ITGB6. Our findings demonstrate that HAX1 can be used as an important biomarker for NPC metastasis, providing a novel basis for antiangiogenesis therapy in clinical settings.

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Biomimetic Hydrogel Scaffolds with Copper Peptide‐Functionalized RADA16 Nanofiber Improve Wound Healing in Diabetes

Yang

Huang

et al. 2022

Macromolecular Bioscience

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Wound healing in diabetes is retarded by the dysfunctional local microenvironment. Although there are many studies using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that can mimic both the structure and functions of natural ECM remain a challenge. Self‐assembling peptide RADA16 nanofiber has distinct advantages to provide a biomimetic extracellular matrix nanofiber structure. However, it still lacks biological cues to promote angiogenesis that is of vital significance for diabetic wound healing. With a customized copper peptide glycyl‐histidyl‐lysine (GHK) functionalized RADA16, an integrated approach using functionalized RADA16 nanofiber to chelate copper ion, is innovatively proposed in this present study. The acquired composite hydrogel holds the biomimetic nanofiber architecture, and exhibits promoting angiogenesis by both enhancing adhesion and proliferation of endothelial cells (EC) in vitro and neovascularization in vivo. It shows that the functionalized nanofiber scaffolds significantly accelerated wound closure, collagen deposition, and tissue remodeling both in healthy and diabetic mice. Furthermore, immunohistochemical analysis give evidence that an upregulated expression of eNOS and CD31 in the copper peptide‐functionalized RADA16 treated group. It can be envisioned that this scaffold can serve as a promising dressing for diabetic wound healing.

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Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1

Cited by 28 publications

References 47 publications

Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel regression during retinal angiogenesis

Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel regression during retinal angiogenesis

Extracellular vesicles rich in HAX1 promote angiogenesis by modulating ITGB6 translation

Biomimetic Hydrogel Scaffolds with Copper Peptide‐Functionalized RADA16 Nanofiber Improve Wound Healing in Diabetes

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