Effect of an AAV1 containing an sh-RNA targeting Angptl2 on the hypocampus of male and female atherosclerotic mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1166667 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cerebral accumulation of inflammatory senescent cells (SnC) may compromise the continuum between endothelial (EC) and neuronal function, leading to vascular cognitive impairment (VCI). We hypothesized that targeted elimination of vascular SnC will preserve cerebrovascular and neuronal functions in atherosclerotic mice of both sexes, demonstrating the causal contribution of SnC in cognitive decline. Male and female atherosclerotic mice (ATX; LDLR-/-;hApoB+/+, n=12 per group) of 6-month of age were treated twice over 3 months with an adeno-associated virus-1 delivering a shRNA targeting vascular Angptl2, a strong inflammatory factor of SnEC; a sh-scramble was used as a control. The Morris water maze test assessed cognition. In males, targeting vascular SnC had no effect on short-term memory but improved long-term memory (p<0.05 vs. sh-scramble); in contrast, in females, the treatment reduced short-term memory (p<0.05), and had no effect on long-term memory. Endothelium-dependent flow-mediated dilations in pressurized cerebral arteries were improved (p<0.05) by the treatment in both males and females. Single-nuclei RNA-sequencing (hippocampal region) revealed a strong sexual dimorphism in transcriptomics profile, with the overexpression of senescence pathways only in male vascular cells. The analysis also revealed that male sex predicted the response to the sh-Angptl2 in oligodendrocytes progenitor cells and neurons (AUC>0.8). Accordingly, the sh-Angptl2 reduced the number of EC expressing angptl2 in males (-75%), but not in females (-10%). In conclusion, these data demonstrate a sexual dimorphism in the causal contribution of vascular senescence in cerebrovascular dysfunction and cognitive impairment: only in male atherosclerotic mice, vascular senescence contributes to VCI.
2025-07-02 | GSE278331 | GEO
Project description:Methanobrevibacter wolinii SH strain:SH Genome sequencing and assembly
| PRJNA223477 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE23303: Gene expression profiling of human atherosclerotic plaque: Laser capture microscopy of smooth muscle cells and macrophages GSE23304: Gene expression profiling of human atherosclerotic plaque: 101 peripheral plaques GSE24495: Gene expression profiling of human atherosclerotic plaque: Carotid plaque GSE24702: Gene expression profiling of human atherosclerotic plaque: 290 peripheral plaques Refer to individual Series
2011-09-30 | E-GEOD-23314 | biostudies-arrayexpress
Project description:We report differential DNA methylation results from human femoral atherosclerotic plaques compared to healthy mammary arteries. 5-methylcytosine containing DNA fragments are captured by methylcytosine binding domain - based MethylCapture assay. Captured fragments are sequenced using Illumina paired-end approach and mapped to human genome (hg19). Results. Hypomethylation of chromosomal DNA predominates in atherosclerotic plaques. Chr14q32.2 was identified for the first time as an extensively hypomethylated area in atherosclerosis with highly induced expression of miR127, -136, -410, -431, and -432
2014-12-01 | GSE53575 | GEO
Project description:The rupture of unstable atherosclerotic plaques, leading to debilitating or fatal thrombotic events, is a major health burden worldwide. Limited understanding as to the molecular drivers of plaque instability and rupture hinders efforts in diagnosis and treatment prior to thrombotic events. Utilising an advanced pre-clinical mouse model (Tandem stenosis (TS) model), which presents human-like unstable atherosclerotic disease, we apply high-end omic methods to characterize the molecular signatures associated with plaque instability in atherosclerotic arteries. Through quantitative proteomic profiling, we depict unique proteome signatures of unstable plaques compared to stable plaques and healthy arteries. Coupled with single-cell RNA-sequencing of leukocytes, we describe the heterodimer complex S100a8/S100a9 as unique to unstable plaque, with neutrophils implicated as the transcriptional drivers of S100a8/a9 expression. We confirm S100a9 expression in human carotid atherosclerotic plaques and we further utilise the TS pre-clinical model to pharmacologically inhibit S100a8/S100a9, resulting in plaque stabilisation. Thus, we establish the TS model as a sophisticated translational tool for the profiling of unstable atherosclerotic plaques and demonstrate that unstable and stable atherosclerosis are highly different disease entities.
2023-05-10 | PXD030857 | Pride
Project description:Inhibition of miR-33 results in increased cholesterol efflux and HDL-cholesterol levels in mice. In this study we examined the effect of miR-33 inhibition in a mouse model of atherosclerosis and observed significant reduction in atherosclerotic plaque size. At the end of the study, gene expression in macrophages from the atherosclerotic plaques was assessed. The results demonstrated a reduction in inflammatory gene expression and increased levels of mRNAs containing miR-33 binding sites.
2011-05-20 | GSE28783 | GEO
Project description:Bacillus pumilus strain:SH-9 | isolate:SH-9 Genome sequencing
| PRJNA1056679 | ENA
Project description:TERT promoter muatations occur frequently in tumors of various origin. We here accessed the frequency of TERT pomoter mutations in 131 human primary neuroblastomas and 20 human neuroblastoma cell lines. No TERT promoter mutations were found in the 131 primary neuroblastomas. However, in the three cell lines SH-SY5Y, SH-EP and SK-N-SH a TERT promoter mutation was detected. Sanger sequencing indicated a homozygous mutation. To confirm loss of heterozygosity (LOH) we performed Affymetrix CytoScanHD SNP arrays. Indeed LOH could be confirmed.
2015-03-03 | GSE66422 | GEO
Project description:The study is to explore differentially expressed genes in SW-1990 cells infected with sh-Ctrl or sh-PRLR.
2020-09-13 | GSE146951 | GEO