Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells

Silva, Juliete A.F.; Qi, Xiaoping; Grant, Maria B.; Boulton, Michael E.

doi:10.1038/s41598-021-96964-7

Cited by 6 publications

(3 citation statements)

References 53 publications

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“…4 – 8 ). VEGFR2 was detected in the nucleus, as previously reported [ 30 , 55 ], and in mitochondria, a novel observation to the best of our knowledge (Fig. 4 , panels A, B and C).…”

Section: Discussionsupporting

confidence: 87%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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“…4 – 8 ). VEGFR2 was detected in the nucleus, as previously reported [ 30 , 55 ], and in mitochondria, a novel observation to the best of our knowledge (Fig. 4 , panels A, B and C).…”

Section: Discussionsupporting

confidence: 87%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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“…2) and by IGEM which also showed the distribution of OT-R and V1aR (Figures 3-7). VEGFR2 was detected in the nucleus, as previously reported 27,53 , and in mitochondria, a novel observation to the best of our knowledge (Fig. 3, panels A, B and C).…”

Section: Discussionsupporting

confidence: 86%

Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor

Ho¹,

Chaput²,

Sinkey³

et al. 2023

Preprint

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VEGFR2 is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX and PICALM. The oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages. MDMX, PICALM, and V1aR were on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before labor. We found select associations between higher MDMX, PICALM, OT-R and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations between PICALM-OT-R (p<2.7x10-8), PICALM-V1aR (p<0.006), and OT-R-V1aR (p<0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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“…The receptor location is an important factor that regulates the access of the ligands and, therefore, its activation. 61 Thus, cytoplasmic accumulation of VEGFR2 could reduce its exposure to VEGF 165 , altering its activation. The analysis of the images (Fig.…”

Section: Resultsmentioning

confidence: 99%

(R,S)-Equol 7-β-D-glucuronide, but not other circulating isoflavone metabolites, modulates migration and tubulogenesis in human aortic endothelial cells targeting the VEGF pathway

Giménez-Bastida,

Ávila-Gálvez,

Martínez-López

et al. 2024

Food Funct.

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Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells

Cited by 6 publications

References 53 publications

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor

(R,S)-Equol 7-β-D-glucuronide, but not other circulating isoflavone metabolites, modulates migration and tubulogenesis in human aortic endothelial cells targeting the VEGF pathway

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