Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage

ABSTRACT: Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. AM plays critical roles in blood vessels, including regulation of vascular stability and permeability. To elucidate the autocrine / paracrine function of AM in endothelial cells in vivo. A conditional knockout of AM in endothelial cells (AM EC-KO) was used. The amount of vascularization the matrigel implants was lower in AM EC-KO mice indicating a defective angiogenesis. Moreover, ablation of AM in endothelial cells revealed increased vascular permeability in comparison with wildtype littermates. In addition, AM EC-KO lungs exhibited significantly less tumor growth than littermate WT mice using a syngeneic model of metastasis. Furthermore, following middle cerebral artery permanent occlusion, there was a significant infarct size decrease in animals lacking endothelial AM when compared to their wild type counterparts. AM is an important regulator of EC function, angiogenesis, tumorigenesis and brain response to ischemia. Studies of AM should bring novel approaches to the treatment of vascular diseases. Lung endothelial mRNA profiles of wild type (WT) and adrenomedullin endothelial cell conditional knockout (AM EC-KO) mice were generated by deep sequencing using Illumina GAIIx.

ORGANISM(S): Mus musculus

SUBMITTER: Laura Ochoa-Callejero

PROVIDER: E-GEOD-84345 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage

Project description:Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. AM plays critical roles in blood vessels, including regulation of vascular stability and permeability. To elucidate the autocrine / paracrine function of AM in endothelial cells in vivo. A conditional knockout of AM in endothelial cells (AM EC-KO) was used. The amount of vascularization the matrigel implants was lower in AM EC-KO mice indicating a defective angiogenesis. Moreover, ablation of AM in endothelial cells revealed increased vascular permeability in comparison with wildtype littermates. In addition, AM EC-KO lungs exhibited significantly less tumor growth than littermate WT mice using a syngeneic model of metastasis. Furthermore, following middle cerebral artery permanent occlusion, there was a significant infarct size decrease in animals lacking endothelial AM when compared to their wild type counterparts. AM is an important regulator of EC function, angiogenesis, tumorigenesis and brain response to ischemia. Studies of AM should bring novel approaches to the treatment of vascular diseases.

2016-08-14 | GSE84345 | GEO

A role for CPT1A to prevent blood vessel permeability revealed by in depth proteomics

Project description:Endothelial cells (ECs) line the inner wall of blood vessels and maintain vascular stability. Vascular stability alteration is a hallmark of pathologies such as cancer and thrombosis. A role for fatty acid oxidation (FAO) in this process is unknown. Integrating MS-proteomics and metabolic modeling revealed that FAO increases when ECs cultured on matrigel are assembled into a fully formed network. Inhibition of CPT1A in ECs, a limiting enzyme in FAO, results in disruption of this network. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which can be restored replenishing the tricarboxylic acid cycle (TCAc). Phosphoproteomic changes upon acute CPT1A inhibition evoked those triggered by thrombin, a potent inducer of EC permeability through calcium signaling. Indeed, CPT1A inhibition increased EC permeability and vascular leakage, which were restored replenishing the TCAc or, partially, inhibiting calcium influx. Our study shows the possibility of altering FAO to interfere with ECs in diseases.

2015-01-28 | PXD001186 | Pride

Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle by inducing capillary sprouting and decreasing vascular permeability via reduced eNOS activity

Project description:Rationale: Slit2 is a possible modulator of vascular endothelial growth factor (VEGF) - induced angiogenesis, but its effects have not been tested in large animal models. Objective: We studied the effect of Slit2 on therapeutic angiogenesis induced by VEGF receptor 2 (VEGFR2) ligands Vammin and VEGF-DΔNΔC in vivo in rabbit skeletal muscles. The Slit2 target genes were also studied by RNA sequencing (RNA-Seq) in endothelial cells. Methods and Results: Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Signaling experiments and gene expression analyses were performed to study mechanisms of Slit2 action. Slit2 decreased VEGFR2-mediated vascular permeability. It also reduced VEGFR2-mediated increase in blood perfusion and capillary enlargement, whereas sprouting of the capillaries was increased. Slit2 gene transfer alone did not have any effects on vascular functions or morphology. VEGFR2 activation was not affected by Slit2, but eNOS phosphorylation was diminished. The transcriptome profiling showed Slit2 downregulating angiogenesis-related genes such as nuclear receptor subfamily 4 group A member 1 (NR4A1) and Stanniocalcin-1 (STC-1) as well as genes related to endothelial cell migration and vascular permeability. Conclusions: Combining Slit2 with VEGFs adjusts VEGFR2-mediated angiogenic effects into a more physiological direction. This possibly allows the use of higher VEGF vector doses to achieve a more widespread vector and VEGF distribution in the target tissues leading to a better therapeutic outcome while reducing excess vascular permeability. HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.

2015-05-26 | E-GEOD-63283 | biostudies-arrayexpress

Programming to S1PR1+ Endothelial Cell Promotes Restoration of Lung Vascular Integrity

Project description:Increased endothelial permeability and failure to repair is the hallmark of several vascular diseases including acute lung injury (ALI). However, little is known about the intrinsic pathways that activate endothelial cell (EC) regenerative programs and thereby tissue repair. Studies have invoked a crucial role of sphingosine-1-phosphate (S1P) in resolving endothelial hyperpermeability through activation of the G-protein coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1). Here, we addressed mechanisms of generation of S1PR1+ EC, which may prevent endothelial injury. Studies were made using inducible EC-S1PR1-/- (iEC-S1PR1-/-) mice and S1PR1-GFP reporter mice to trace the generation of S1PR1+ EC. We observed in a mouse model of endotoxemia that S1P generation induced the programming of S1PR1lo to S1PR1+ EC, which comprised 80% of lung EC. The transition of these cells was required for reestablishing the endothelial barrier. We also observed that conditional deletion of S1PR1 in EC increased vascular permeability. RNA-seq analysis of S1PR1+ EC showed enrichment of genes regulating S1P synthesis and transport, sphingosine kinase 1 (SPHK1) and SPNS2, respectively. The activation of transcription factors EGR1 and STAT3 were essential for transcribing SPHK1 and SPNS2, respectively, to increase S1P production that served to amplify S1PR1+ EC transition. Transplantation of S1PR1+ EC into injured lung vasculature restored endothelial integrity. Our findings show that generation of a S1PR1+ EC population activates the endothelial regenerative program mediating vascular endothelial repair, thus raising the possibility of harnessing this pathway to restore vascular homeostasis in inflammatory injury.

2023-01-15 | GSE165000 | GEO

Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor [RNA-Seq]

Project description:Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF. In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity. Examination of PR target genes in human umbilical vein endothelial cells (HUVECs) using RNA-seq (PR infected only -PR only and PR infected followed by ligand treatment-PR+P)

2014-01-01 | E-GEOD-43788 | biostudies-arrayexpress

Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor [ChIP-Seq]

Project description:Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF. In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity. Examination of PR binding sites in HUVEC cells using ChIP-seq (non-infected-negative control, PR infected followed by ligand treatment-PR+P or vehicle PR)

2014-01-01 | E-GEOD-43786 | biostudies-arrayexpress

Endothelial TGFβ signaling drives vascular inflammation and atherosclerosis [scRNA-Seq]

Project description:Endothelial TGFβ signaling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGFβ signaling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. We performed scRNAseq method to examine endothelial cell gene expression profile using Apoe and EC specific TGFbR1/2 KO in Apoe background mice.

2019-08-26 | GSE134557 | GEO

Endothelial TGFb signaling drives vascular inflammation and atherosclerosis [ChIP-Seq]

2019-08-26 | GSE134556 | GEO

Endothelial TGFb signaling drives vascular inflammation and atherosclerosis [bulk RNA-Seq]

2019-08-26 | GSE134555 | GEO

Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle by inducing capillary sprouting and decreasing vascular permeability via reduced eNOS activity

2015-05-26 | GSE63283 | GEO