The effects of AAV-VEGF-B and deletion of endothelial VEGFR1 on heart transcriptome in adult mice
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ABSTRACT:
PROVIDER: PRJNA433943 | ENA |
REPOSITORIES: ENA
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Project description:We evaluated the effects of vascular endothelial growth factor -B (VEGF-B) and the deletion of its receptor VEGFR1 from endothelial cells on cardiac hypertrophy. Whole-genome transcriptomic analysis showed that overexpression of the ligand had similar effects on the heart transcriptome as deletion of its receptor. Both treatments also induced angiogenesis and mild cardiac hypertrophy. The aim of the study was to identify pathways, which mediate angiogenesis-induced cardiac hypertrophy.
2018-12-31 | GSE110532 | GEO
Project description:We have previously reported that mice expressing a cardiomyocyte-specific αMHC-VEGF-B transgene in the heart show a clear expansion of the coronary vasculature and cardiac hypertrophy, without significant changes in heart function. As a therapeutic way of administrating VEGF-B protective effects, we show that AAV-VEGF-B induces the proliferation of endothelial cells (EC). All the samples were analyzed using the Chromium Single-cell 3'RNA-sequencing system.
2022-03-15 | GSE128509 | GEO
Project description:We show that an excess of VEGF-B protects the heart via adaptive cardiac hypertrophy and increased coronary arterial reserve, and by inducing a shift from lipid to glucose metabolism. Six hearts transduced with AAV-VEGF-B were compared to six AAV-HSA (human serum albumin) controls
2013-11-30 | E-GEOD-38455 | biostudies-arrayexpress
Project description:Overcoming vascular immunosuppression: lack of endothelial cell (EC) responsiveness to inflammatory stimuli in the proangiogenic environment of tumors, is essential for successful cancer immunotherapy. The mechanisms through which Vascular Endothelial Growth Factor (VEGF) modulates tumor EC response to exclude T cells are not well understood. The goal was to determine the role of EC Rap1B, a small GTPase that positively regulates VEGF-angiogenesis during development, in tumor growth in vivo. Using mouse models of Rap1B deficiency, Rap1B+/- and endothelial-specific Rap1B KO (Rap1BiΔEC) we demonstrate Rap1B restricts tumor growth and angiogenesis. More importantly, EC-specific Rap1B deletion leads to an altered tumor microenvironment with increased recruitment of leukocytes and increased activity of tumor CD8+ T cells. We find that tumor growth, albeit not angiogenesis, is restored in Rap1BiΔEC mice by depleting CD8+ T cells. Mechanistically, global transcriptome analysis indicated upregulation of the TNF-α signaling and cytokine-induced NFκB transcriptional activity in Rap1B-deficient ECs. In particular, endothelial Rap1B deletion led to upregulation of Cell Adhesion Molecules (CAMs) expression in response to proinflammatory cytokines, and increased interaction with leukocytes in vitro. Importantly, deletion of Rap1 abrogated VEGF-mediated inhibition of CAM expression, demonstrating that Rap1B is essential for mediating VEGF-suppressive signaling. Thus, our studies identify a novel endothelial-endogenous mechanism underlying VEGF-dependent desensitization of EC to pro-inflammatory stimuli. Significantly, they identify EC Rap1 as a potential novel vascular target in cancer immunotherapy.
2022-11-21 | GSE186046 | GEO
Project description:Endothelial Rap1B mediates VEGF immunosuppression
| PRJNA772189 | ENA
Project description:Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intra-cerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth, and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon ligation of the dCLN afferent lymphatics, and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.
2024-02-27 | GSE252622 | GEO
Project description:Doxorubicin is a widely used and effective anthracycline chemotherapy drug, which use is limited due to its cardiotoxic side effects. We show that gene therapy with AAV-VEGF-B can inhibit the doxorubicin-induced cardiac atrophy and whole body cachexia.
2016-09-30 | GSE81448 | GEO
Project description:Objective: Dyslipidemia is one of the key factors behind coronary heart disease. Blood and lymphatic vessels play pivotal roles in both lipoprotein metabolism and development of atherosclerotic plaques. Recent studies have linked members of Vascular Endothelial Growth Factor (VEGF) family to lipid metabolism but the function of VEGF-D has remained unexplored. Here we investigated how the deletion of VEGF-D affects lipid and lipoprotein metabolism in atherogenic LDLR-/-ApoB100/100 mice. Approach and Results: Deletion of VEGF-D (Vegfd-/-LDLR-/-ApoB100/100) led to markedly elevated plasma cholesterol and triglyceride levels without an increase in atherogenesis. Size distribution and hepatic lipid uptake studies confirmed a delayed clearance of large chylomicron remnant particles that cannot easily penetrate through the vascular endothelium. Mechanistically, the inhibition of VEGF-D signaling significantly decreased the hepatic expression of syndecan 1 (SDC1), which is one of the main receptors for chylomicron remnant uptake when LDLR is absent. Immunohistochemical staining confirmed reduced expression of SDC1 in the sinusoidal surface of hepatocytes in VEGF-D deficient mice. Furthermore, hepatic RNA sequencing revealed that VEGF-D is also an important regulator of genes related to lipid metabolism and inflammation. The lack of VEGF-D signaling via VEGF receptor 3 led to lowered expression of genes regulating triglyceride and cholesterol production as well as downregulation of peroxisomal β-oxidation pathway. Conclusions: These results demonstrate that VEGF-D, a powerful lymphangiogenic and angiogenic growth factor, is also a major regulator of chylomicron metabolism in mice.
2018-08-16 | GSE108959 | GEO
Project description:Changes in whole heart gene expression resulting from endothelial TLR2 deletion
| PRJNA648401 | ENA
Project description:Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intra-cerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth, and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon ligation of the dCLN afferent lymphatics, and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.
2024-01-18 | GSE253051 | GEO