Similar Datasets
Project description:Cardiovascular diseases (CVDs) are leading causes of death worldwide. Endothelial dysfunction is a critical initiating factor contributing to CVDs, which progression involves the gut microbiome-derived metabolite Trimethylamine N-oxide (TMAO). Here, we aim to clarify the time-dependent pathways by which TMAO mediates endothelial dysfunction.
2023-11-23 | GSE235204 | GEO
Project description:Liver cancer has a high mortality rate. Chronic inflammation is one of the leading causes of hepatocellular carcinoma. Recent studies suggested high levels of trimethylamine N-oxide (TMAO) may correlate with increased risk of inflammatory-induced liver cancer. However, the mechanisms by which TMAO promotes liver cancer remain elusive. Here, we established a model of inflammatory-induced liver cancer by treating Hepa1-6 cells with TNF-α. TMAO synergistically increased the proliferation, migration and invasion of Hepa1-6 cells in the presence of TNF-α. We conducted bulk RNA-Seq of the TMAO-treated cell model of inflammatory Hepatocellular carcinoma (HCC)
2022-01-18 | GSE193557 | GEO
Project description:In vivo work done to determine how trimethylamine N-oxide (TMAO) affects integrity of the blood-brain barrier. Wild-type male C57Bl/6 mice were injected with saline or TMAO (1.8 mg/kg in saline), and killed 2 h after injection. Mice were transcardially perfused with 0.9% saline at 4 °C to remove circulating blood, and brains were removed and collected into RNAlater. Whole brain total RNA was extracted using a PureLink RNA Mini Kit. RNA samples (n=3 TMAO, n=3 control) were sent to Macrogen Inc. (Republic of Korea) where they were subject to quality checks (RIN analysis), library prep and sequencing [TruSeq Stranded mRNA LT Sample Prep Kit; paired-end (2x 100 nt) sequencing; Illumina HiSeq 4000].
2020-12-19 | E-MTAB-9869 | biostudies-arrayexpress
Project description:Trimethylamine N-oxide (TMAO), a metabolite derived from intestine microbial flora, enhances vascular inflammation in a variety of cardiovascular disease, and the bacterial communities associated with trimethylamine N-oxide (TMAO) metabolism is higher in pulmonary hypertension (PH) patients. The effects of TMAO on PH, however, has not been elucidated. In the present study, we found that circulating TMAO is elevated in intermediate to high-risk PH patients when compared to healthy control or low-risk PH patients. In monocrotaline-induced rat PH models, circulating TMAO is elevated; and reduction of TMAO using 3,3-dimethyl-1-butanol (DMB) significantly decreased right ventricle systolic pressure, pulmonary vascular muscularization in both monocrotaline-induced rat PH and hypoxia induced mice PH models. RNA sequencing of rat lungs on DMB revealed significant suppression of pathways involved in cytokine-cytokine receptor interaction, and cytokine and chemokine signaling. Protein-protein interaction analysis of the differentially expressed transcripts regulated by DMB showed 5 hub genes with a strong connectivity of proinflammatory cytokines and chemokines including Kng1, Cxcl1, Cxcl2, CxcL6 and Il6. In vivo, TMAO significantly increased the expression of Kng1, Cxcl1, Cxcl2, CxcL6 and Il6 in bone marrow derived macrophage. And TMAO-treated conditioned medium from macrophage increased the proliferation and migration of pulmonary artery smooth muscle cells; but TMAO treatment did not change the proliferation or migration of pulmonary artery smooth muscle cells. In conclusion, our study demonstrates that TMAO is increased in severe PH, and the reduction of TMAO using DMB reduces pulmonary vascular muscularization and alleviates PH via suppressing the macrophage production of chemokines and cytokines.
2022-06-07 | GSE190203 | GEO
Project description:Trimethylamine-N-oxide (TMAO) is a uremic toxin, which has been associated with chronic kidney disease (CKD). Renal tubular epithelial cells play a central role in the pathophysiology of CKD. Megalin is an albumin-binding surface receptor on tubular epithelial cells, which is indispensable for urine protein reabsorption. To date, no studies have investigated the effect of TMAO on megalin expression and the functional properties of human tubular epithelial cells. The aim of this study was first to identify the functional effect of TMAO on human renal proximal tubular cells and second, to unravel the effects of TMAO on megalin-cubilin receptor expression. We found through global gene expression analysis that TMAO was associated with kidney disease. The microarray analysis also showed that megalin expression was suppressed by TMAO, which was also validated at the gene and protein level. High glucose and TMAO was shown to downregulate megalin expression and albumin uptake similarly. We also found that TMAO suppressed megalin expression via PI3K and ERK signaling. Furthermore, we showed that candesartan, dapagliflozin and enalaprilat counter-acted the suppressive effect of TMAO on megalin expression. Our results may further help us un-ravel the role of TMAO in CKD development and to identify new therapeutic targets to counteract TMAOs effects.
2022-08-10 | GSE210692 | GEO
Project description:Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide(TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT), and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.
2014-12-19 | GSE64326 | GEO
Project description:Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide(TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT), and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic ER stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation. To identify potential regulators of macrophage reverse cholesterol transport (RCT), liver was isolated from two independent mouse models where the non-biliary RCT pathway known as transintestinal cholesterol excretion (TICE) was either chronically (NPC1L1-liver-transgenic mice) or acutely (ACAT2 antisense oligonucleotide treatment) stimulated. Total RNA was isolated and gene expression levels were profiled on the Affymetrix GeneAtlas MG-430 PM Array Strip (Affymetrix; Santa Clara, CA, USA)
2014-12-19 | E-GEOD-64326 | biostudies-arrayexpress
Project description:Next Generation Sequencing of TMAO (Trimethylamine N-oxide)-treated Cardiac Transcriptomes
| PRJNA532642 | ENA
Project description:Vascular dementia (2VO) is the second-most cause of dementia, and our previous investigation showed that Trimethylamine-N-oxide (TMAO) exacerbates cognitive dysfunction and neuropathological changes in 2VO rats. Therefore, this study is aimed to evaluate the mechanism of TMAO in 2VO. Bilateral common carotid artery (2VO) model was established in rats and TMAO (120 mg/kg) was administered for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was performed to find out the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was conducted to identify potential downstream targets. Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr was highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats. Taken together, our results showed that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of 2VO.
2024-10-30 | GSE249873 | GEO
Project description:Transcriptional profiling of human aortic smooth muscle cells (HSMCs) comparing exposed with nicotine or not. Two-condition experiment, control vs. treated HSMCs by nicotine.
2015-04-15 | E-GEOD-56383 | biostudies-arrayexpress