VEGF receptors mediate hypoxic remodeling of adult ovine carotid arteries

Adeoye, Olayemi; Bouthors, Vincent; Hubbell, Margaret C.; Williams, James M.; Pearce, William J.

doi:10.1152/japplphysiol.00012.2014

Cited by 14 publications

(11 citation statements)

References 62 publications

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“…Age is also a critical factor in remodeling responses to hypoxia 33–35 due in large part to developmental and maturational differences in the populations of cell surface receptors on the smooth muscle cells for both RTK-dependent and GPCR dependent vasotrophic factors such as VEGF 15 and endothelin-1 19,36 . For VEGF, receptor levels for both the FLT and FLK types are expressed at lower levels in fetal than adult arteries, and hypoxia dramatically increases both receptor types in both age groups 37,38 . Hypoxia also increases expression of endothelin-A receptors in fetal cerebral arteries 36 .…”

Section: Effects Of Hypoxia On Cerebrovascular Structure and Functionmentioning

confidence: 99%

Fetal Cerebrovascular Maturation: Effects of Hypoxia

Pearce

2018

Seminars in Pediatric Neurology

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The human cerebral vasculature originates in the fourth week of gestation and continues to expand and diversify well into the first few years of postnatal life. A key feature of this growth is smooth muscle differentiation, whereby smooth muscle cells within cerebral arteries transform from migratory to proliferative to synthetic and finally to contractile phenotypes. These phenotypic transformations can be reversed by pathophysiological perturbations such as hypoxia, which causes loss of contractile capacity in immature cerebral arteries. In turn, loss of contractility affects all whole-brain cerebrovascular responses, including those involved in flow-metabolism coupling, vasodilatory responses to acute hypoxia and hypercapnia, cerebral autoregulation, and reactivity to activation of perivascular nerves. Future strategies to minimize cerebral injury following hypoxia-ischemic insults in the immature brain might benefit by targeting treatments to preserve and promote contractile differentiation in the fetal cerebrovasculature. This could potentially be achieved through inhibition of RTK mediated growth factors, such as VEGF and PDGR, which are mobilized by hypoxic and ischemic injury and which facilitate contractile dedifferentiation. Interruption of the effects of other vascular mitogens, such as endothelin and angiotensin-II, and even some miRNA species, also could be beneficial. Future experimental work that addresses these possibilities offers promise to improve current clinical management of neonates who have suffered and survived hypoxic, ischemic, asphyxic, or inflammatory cerebrovascular insults.

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Section: Effects Of Hypoxia On Cerebrovascular Structure and Functionmentioning

confidence: 99%

Fetal Cerebrovascular Maturation: Effects of Hypoxia

Pearce

2018

Seminars in Pediatric Neurology

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“…In the present study, FAP and VEGF-A expression levels were determined in MG63, U2-OS and HOS cells. Vessel endothelial cells line the inner walls of blood vessels and serve a critical role in angiogenesis (22). Under the control of angiogenic factors derived from multiple types of cell, including pericytes and tumor cells, vessel endothelial cells began to proliferate and migrate, resulting in angiogenesis (7,23).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast activation protein in osteosarcoma cells promotes angiogenesis via AKT and ERK signaling pathways

Zeng

Wen

Liu³

2018

Oncol Lett

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Abstract. Although it is established as a marker of cancer-associated fibroblasts, the expression of fibroblast activation protein (FAP) is not restricted to stromal cells; its expression in multiple types of tumor cell and its pro-tumor functions have been reported. However, the role of FAP in angiogenesis in osteosarcoma remains uncharacterized. In the present study, it was identified that the mRNA and protein expression levels of FAP and vascular endothelial growth factor-A (VEGF-A) corresponded to each other in MG63, U2-OS and HOS osteosarcoma cells. Subsequent to upregulating FAP in MG63 cells, VEGF-A mRNA and protein expression significantly increased; subsequent to downregulating FAP in U2-OS cells, VEGF-A mRNA and protein expression significantly declined. These changes in VEGF-A level were also detected in the cell supernatant with ELISA. Conditioned medium (CM) from MG63 cells overexpressing FAP promoted the phosphorylation of AKT and extracellular signal-regulated kinase (ERK) in human umbilical vein endothelial cells (HUVECs), as well as the proliferation rate. The CM from U2-OS cells with FAP knockdown inhibited the proliferation rate of HUVECs. The phosphorylation of AKT and ERK was increased in MG63 cells overexpressing FAP, but reduced in U2-OS cells with FAP knockdown. Furthermore, treatment with the AKT inhibitor LY294002 or the ERK inhibitor U0126 inhibited the upregulation of VEGF-A induced by FAP expression. Collectively, the results suggest that FAP expression in osteosarcoma cells promotes angiogenesis.

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“…VEGFR-2 is an essential mediator of VEGF-initiated angiogenesis and serves crucial roles in regulating multiple signaling pathways in endothelial cells which may regulate core angiogenic responses, including proliferation, migration and tube formation abilities (26,27). The Akt and ERK signaling pathways are crucial participants in maintaining the different biological behaviors of different cells including proliferation, migration, differentiation, drug resistance, apoptosis and phenotype maintenance (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast activation protein-α in tumor cells promotes colorectal cancer angiogenesis via the Akt and ERK signaling pathways

Cao

Wang

et al. 2017

Mol Med Report

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Fibroblast activation protein-α (FAP-α) is a cell surface serine protease of the post-prolyl peptidase family, and stromal FAP-α expression may serve important functions in tumor occurrence and progression. In recent years, FAP-α expression in tumor cells has been detected in a number of types of tumor, and its roles in tumor growth and metastasis have been reported. However, the presence of FAP-α in colorectal cancer (CRC) cells lacks sufficient evidence and its role in angiogenesis remains unknown. The present study confirmed FAP-α expression in CRC cells at the tissue and cellular level, using immunohistochemistry and western blot analysis, respectively; it additionally identified that FAP-α in CRC cells was positively associated with vascular endothelial growth factor (VEGF)-A expression and microvessel density in stained tissue samples for the first time. In addition, western blotting identified that FAP-α overexpression in SW1116 cells significantly upregulated VEGF-A expression, and silencing of FAP-α in HT29 cells markedly inhibited VEGF-A expression. Survival analysis demonstrated that patients with high expression of FAP-α and VEGF-A had the shortest survival time. To detect the effects of FAP-α on human umbilical vein endothelial cells (HUVECs), conditioned medium (CM) from CRC cell lines was used and it was identified that CM from SW1116 cells with overexpressed FAP-α exhibited significantly increased VEGF-R2, phosphorylated extracellular signal-regulated kinase (p-ERK) and p-RAC-α serine/threonine-protein kinase (Akt) in HUVECs, in addition to the proliferation rate. Conversely, CM from HT29 cells with FAP-α silenced exhibited a significantly inhibited proliferation rate. Molecular mechanism analysis demonstrated that p-ERK and p-Akt in SW1116 and HT29 cells were affected by alterations in FAP-α expression, and treatment with a p-ERK inhibitor (U0126) and p-Akt inhibitor (LY294002) ameliorated VEGF-A upregulation induced by FAP-α overexpression. All the results confirmed the presence of FAP-α in CRC cells and suggested that FAP-α may effectively promote angiogenesis in CRC via the Akt and ERK signaling pathways.

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VEGF receptors mediate hypoxic remodeling of adult ovine carotid arteries

Cited by 14 publications

References 62 publications

Fetal Cerebrovascular Maturation: Effects of Hypoxia

Fetal Cerebrovascular Maturation: Effects of Hypoxia

Fibroblast activation protein in osteosarcoma cells promotes angiogenesis via AKT and ERK signaling pathways

Fibroblast activation protein-α in tumor cells promotes colorectal cancer angiogenesis via the Akt and ERK signaling pathways

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