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Project description:Endothelial Gsα regulates post-ischemia angiogenesis
| PRJNA852788 | ENA
Project description:Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs was strikingly up-regulated in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, the overexpression of tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Our results indicate that tRNA-derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells. Examine small RNAs involved in post-ischemia angiogenesis
2016-03-16 | E-GEOD-70473 | biostudies-arrayexpress
Project description:Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs was strikingly up-regulated in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, the overexpression of tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Our results indicate that tRNA-derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells.
2016-03-16 | GSE70473 | GEO
Project description:Acid sphingomyelinase (ASM) inhibitors, which are clinically used as anti-depressants for ~60 years, have recently been shown to enhance stroke recovery in rodents. Using mice and cerebral microvascular endothelial cells exposed to ischemia/reperfusion (I/R) we show that the antidepressants amitriptyline, fluoxetine and desipramine induce angiogenesis in an ASM-dependent way by releasing small extracellular vesicles (sEVs) from endothelial cells, which have bona fide characteristics of exosomes and which, similar to sEVs released during I/R, promote angiogenesis. Post-I/R, ASM inhibition elicits a profound brain remodeling response with increased blood-brain barrier integrity, reduced brain leukocyte infiltrates and increased neuronal survival. The ASM inhibitor-mediated release of sEVs has disclosed an elegant target, via which stroke recovery can be amplified. Key words: Antidepressant, ceramide, exosome, focal cerebral ischemia, middle cerebral artery occlusion, sphingomyelin, stroke recovery
2022-10-14 | PXD024106 | Pride
Project description:Impaired post-ischemic angiogenesis in rats with chronic kidney disease: underlying changes in ischemia-induced early regulation of gene expression We investigated potential molecular mechanisms underlying impaired angiogenesis by a systematic comparison of early gene expression in response to ischemia in rats with or without CKD
2016-10-20 | GSE88925 | GEO
Project description:Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C+macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC+CXCR2+ macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.
2024-08-02 | GSE273730 | GEO
Project description:Angiogenesis, the formation of new blood vessels from pre-existing ones, is a complex and demanding biological process that plays an important role in physiological as well as pathological settings such as cancer and ischemia. Given its critical role, the regulation of endothelial growth factor receptor (e.g. VEGFR2, FGFR1) represents important mechanisms for the control of angiogenesis. Recent evidences support cell metabolism as a critical regulator of angiogenesis. However, it is unknown how glutamine metabolism regulates growth factor receptor expression. Here, by using genetic and pharmacological approaches, we show that glutaminolysis and glutamate-dependent transaminases (TAs) support alpha-ketoglutarate (αKG) levels and are critical regulators of angiogenic response during pathological conditions. Indeed, the endothelial specific blockage of GLS1 impairs ischemic and tumor angiogenesis by suppressing VEGFR2 translation via mTORC1-dependent pathway. Lastly, we discover that ECs catabolized the glutamine-derived glutamate via phosphoserine aminotransferase 1 (PSAT1) as crucial to support VEGFR2 translation. These findings identify glutamine anaplerosis and TA activity as a critical regulator of growth factor receptor translation in normal and pathological angiogenesis. We anticipate our studies to be a starting point for novel anti-angiogenesis approaches based on GLS1/PSAT1 inhibitor treatments to overcome anti-VEGF therapies resistance.
2022-04-22 | PXD022379 | Pride
Project description:Efficient angiogenesis, the formation of new blood vessels from pre-existing vessels, underlie tissue growth during development. Blood vessels in the mouse ear has been shown to dramatically expand at the neonatal stage to meet the needs of postnatal tissue growth. Yet, it is not clear at the transcriptome level how endothelial cells lining the innermost layer of blood vessels drive angiogenesis at this developmental stage. The highly heterogeneous endothelial cell types during angiogenesis render traditional bulk RNA-sequencing unsuitable. Therefore, we utilized single-cell RNA- and CITE-seq to profile transcriptomic heterogeneity of both blood and lymphatic endothelial cells during developmental angiogenesis in mouse ear.
2024-04-29 | GSE216594 | GEO
Project description:Arterial and venous endothelial cells exhibit distinct molecular characteristics at early developmental stages. These lineage-specific molecular programs are instructive to the development of distinct vascular architectures and physiological conditions of arteries and veins, but their roles in angiogenesis remain unexplored. Here, we show that the caudal vein plexus in zebrafish forms by endothelial cell sprouting, migration and anastomosis, providing a venous-specific angiogenesis model. Using this model, we identified a novel compound, aplexone, which effectively suppresses venous, but not arterial, angiogenesis. Multiple lines of evidence indicate that aplexone differentially regulates arteriovenous angiogenesis by targeting the HMG-CoA reductase (HMGCR) pathway. Treatment with aplexone affects the transcription of enzymes in the HMGCR pathway and reduces cellular cholesterol levels. Injecting mevalonate, a metabolic product of HMGCR, reverses the inhibitory effect of aplexone on venous angiogenesis. In addition, aplexone treatment inhibits protein prenylation and blocking the activity of geranylgeranyl transferase induces a venous angiogenesis phenotype resembling that observed in aplexone-treated embryos. Furthermore, endothelial cells of venous origin have higher levels of proteins requiring geranylgeranylation than arterial endothelial cells and inhibiting the activity of Rac or Rho Kinase effectively reduces the migration of venous, but not arterial, endothelial cells. Taken together, our findings indicate that angiogenesis is differentially regulated by the HMGCR pathway via an arteriovenousdependent requirement for protein prenylation in zebrafish and human endothelial cells.
2011-01-11 | E-MTAB-494 | biostudies-arrayexpress
Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis Two series of 4 mice each were treated with either control adenovirus (AdNull) or adenovirus expressing neurotrophin p75 receptor (AdP75). Anaesthetized mice received 3 adenovirus injections (for a total of 109 p.f.u. virus in 20 micro L) into 3 equidistant sites of the normoperfused or ischemic left adductor muscles, as described (2. Emanueli C, Graiani G, Salis MB, Gadau S, Desortes E, Madeddu P. Prophylactic gene therapy with human tissue kallikrein ameliorates limb ischemia recovery in type 1 diabetic mice. Diabetes. 2004 Apr;53(4):1096-103. )
2010-06-25 | E-GEOD-9910 | biostudies-arrayexpress