Impaired post-ischemic angiogenesis in rats with chronic kidney disease
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE88925 | GEO | 2016/10/20
SECONDARY ACCESSION(S): PRJNA349132
REPOSITORIES: GEO
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Project description:Diabetes is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis or increased endothelial cell apoptosis. Here is it shown that angiogenic repair of ischemic hind limbs was impaired in Lepr db/db mice, a leptin receptor deficient model of diabetes, compared to wild-type C57BL/6 (WT) mice as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hind limb cDNA expression profiles were created from adductor muscle of Lepr db/db and WT mice before and after hind limb ischemia using Affymetrix GeneChip® Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis related proteins were altered in Lepr db/db versus WT mice following ischemic injury. These transcripts included neuropilin-1, VEGF-A, placental growth factor, elastin and matrix metalloproteinases that are implicated in blood vessel growth and maintenance of vessel wall integrity. These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network. Keywords: Diabetes, ischemia, angiogenesis, microarrays
2014-06-30 | GSE3313 | GEO
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
Project description:infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
2021-03-23 | PXD022212 | Pride
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:In conclusion, the data have identified acetaldehyde as the preferred substrate for Aldh2.1’s detoxification ability. In zebrafish acetaldehyde induces impaired glucose metabolism by blocking gene expression of glucokinase and glucose-6-phosphatase. Moreover, Stress-activated protein Kinases JNK and p38 MAPK were activated by elevated endogenous acetaldehyde leading to increased angiogenesis and vasodilatory effects in aldh2.1-/- zebrafish mutants.
2022-09-07 | GSE189416 | GEO
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
2008-07-17 | GSE9910 | GEO
Project description:Diabetes is a major risk factor of cardiovascular disease including coronary and peripheral arterial disease, attributed to impaired arteriogenesis and angiogenesis. Mechanisms behind them are poorly understood due to the complexity of these processes in presence of diabetes. To understand the cellular and molecular mechanisms underlying impaired adaptive vascular responses in type 2 diabetic (T2DM) mouse models of hindlimb ischemia using Genome-wide mRNA sequencing.In response to FAL, collateral density and lumen area were significantly reduced in adductor muscles of T2DM mice at day 7 and 14 days post-FAL. mRNA sequencing suggested an altered gene expression typical for monocyte and macrophage (Mϕ) subsets. Similarly, gene expressions typical of dendritic cell and lymphocyte were altered in adductor muscles of T2DM mice. Ischemic muscles of T2DM mice displayed impaired angiogenesis as revealed by endothelial staining. mRNA sequencing suggested downregulation of crucial genes implicated in angiogenesis and differential expression of genes typical for Mϕ subsets. Immunohistochemistry analysis corroborated with the mRNA sequencing analysis, suggesting an altered Mϕ polarization behind the impaired arteriogenesis and angiogenesis seen in T2DM mouse models of hindlimb ischemia.
2023-01-30 | GSE69123 | GEO
Project description:Ischemia/reperfusion injuries is a known complication to hepatic surgery. Ischemic pre- (IPC) and postconditioning (IPO) protects the liver against ischemia/reperfusion-injuries. Expression profiling were performed on liver biopsies seeking to identify molecular mediators of the protective properties. 48 rats were divided into 5 groups; sham (n=8), IRI (n=10), IPC (n=10), IPO (n=10) and IPC+IPO (n=10). All rats except sham rats were subjected to 30 min of total liver ischemia and 30 min of reperfusion before liver biopsies were sampled. In the IPC group, liver ischemia was preceded by 10 min of hepatic ischemia, followed by 10 min of reperfusion. IPO were performed by three cycles of 30 sec of reperfusion and 30 sec of ischemia, applied immediately after the 30 min of total liver ischemia. In the IPC+IPO group the two interventions were combined.
2011-09-30 | E-GEOD-24430 | biostudies-arrayexpress
Project description:Background and aims: There are considerable evidences demonstrating that angiogenesis and chronic inflammation are mutually dependent. However, although cirrhosis progression is characterized with a chronic hepatic inflammatory process, this connection is not sufficiently explored as a therapeutic strategy. Therefore, this study was aimed to assess the potential benefits of targeting angiogenesis in cirrhotic livers to modulate inflammation and fibrosis. For this purpose, we evaluate the therapeutic utility of angiogenesis inhibitors. Methods: The in vivo effects of angiogenesis inhibitors were monitored in liver of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, a-smooth muscle actin (a-SMA) accumulation, differential gene expression (by microarrays), and portal pressure. Results: Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1, angiopoietin-2 and placental growth factor (PlGF) in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Interestingly, the expression of these adhesion molecules correlated well with local inflammatory infiltrate. Livers of cirrhotic rats treated with angiogenesis inhibitors presented a significant decrease in hepatic vascular density, inflammatory infiltrate, a-SMA abundance, collagen expression and portal pressure. Conclusion: Angiogenesis inhibitors may offer a potential novel therapy for cirrhosis due to its multiple mechanisms of action against angiogenesis, inflammation and fibrosis in cirrhotic livers. Experiment Overall Design: RNA from liver of 4 non-treated cirrhotic rats or 4 rats treated with angiogenesis inhibitors was hybridized to 8 high-density oligonucleotide microarray (Rat2302, Affymetrix, Santa Clara, CA)
2008-06-15 | E-GEOD-6929 | biostudies-arrayexpress
Project description:Sleep deprivation (SD) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood we used DNA oligonucleotide microarray analysis, to identify the genes and the gene-pathways underlying SD preconditioning. Gene expression was analyzed 3 days after stroke surgery in four experimental groups: i) SD performed before focal cerebral ischemia induction; ii) SD performed before Sham surgery; iii) IS without SD; and iv) Sham surgery without SD. SD was performed by gentle handling during the last 6h of the light period and ischemia was induced immediately after. Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SD induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-M-kM-1-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. Our data indicate that SD before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms.
2015-10-30 | E-MTAB-3148 | biostudies-arrayexpress