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Lipid Droplet-Associated Hydrolase Mobilizes Oxysterol Stores and Inhibits Atheroma Growth and Progression

ABSTRACT: Lipid Droplet-Associated Hydrolase Mobilizes Oxysterol Stores and Inhibits Atheroma Growth and Progression

PROVIDER: PRJNA663469 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12641812_1.fastq.gz	Fastqsanger.gz
	SRR12641812_2.fastq.gz	Fastqsanger.gz
	SRR12641813_1.fastq.gz	Fastqsanger.gz
	SRR12641813_2.fastq.gz	Fastqsanger.gz
	SRR12641814_1.fastq.gz	Fastqsanger.gz

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Lipid Droplet-Associated Hydrolase Mobilizes Oxysterol Stores and Inhibits Atheroma Growth and Progression

Project description:Lipid droplets (LDs) of foam cells within atheroma contain abundant cholesterol, but also serve as reservoirs of central bioactive lipids. The mechanisms of storage and mobilization of many of these lipids remain obscure. LD-associated hydrolase (LDAH) localizes to LDs, has a lipase structure, and is abundant in atheroma. However, its lipid substrates and role in atherogenesis are unknown. Using knockout and transgenic mice we found that LDAH protects against atherosclerosis. Myeloid LDAH expression is sufficient to inhibit lesion progression and promote stable architectures, less necrotic, and richer in fibrillar collagen. Lipidomics coupled with RNA sequencing revealed that LDAH facilitates mobilization of esters of oxysterols that are liver X receptor agonists, leading to induction of cholesterol efflux transporters, reduced foam cell inflammation, and pro-fibrotic gene signatures. These studies identify LDAH as a novel player in neutral hydrolysis of esterified regulatory sterols that promotes atheroprotective and pro-stabilizing mechanisms beyond mass cholesterol removal.

2020-11-10 | GSE157947 | GEO

Genome-wide expression study of human carotid atheroma

Project description:The aim of this study was to identify new biomarkers and to investigate pathways involved in the progression of human carotid atheroma. The study was conducted from pieces of carotid endarterectomy collected in 32 hypertensive patients. The samples contained media and neo-intima without adventitia. They were paired, including for each patient one sample of the atheroma plaque (stage IV and over of the Stary classfication) containing core and shoulders of the plaque, and one sample of distant macroscopically intact tissue (stages I and II). In addition, clinical, biological and histological data were collected.

2013-04-01 | E-GEOD-43292 | biostudies-arrayexpress

Genome-wide expression profiling of human carotid atheroma

2013-04-01 | E-MTAB-1470 | biostudies-arrayexpress

Genome-wide expression study of human carotid atheroma

Project description:The aim of this study was to identify new biomarkers and to investigate pathways involved in the progression of human carotid atheroma.

2013-04-01 | GSE43292 | GEO

Lipid droplet-associated hydrolase mobilizes stores of liver X receptor sterol ligands and protects against atherosclerosis

Project description: Not available

| S-EPMC11297204 | biostudies-literature

Human femoral atheroma exhibit inflammation-resolving myeloid and lymphoid bias compared with carotid atheroma

Project description:Human femoral atheroma exhibit inflammation-resolving myeloid and lymphoid bias compared with carotid atheroma

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Analysis of mixed-oxysterol treatment on the THP-1 macrophage

Project description:THP-1 monocytes were differentiated, via PMA treatment, to macrophages. THP-1 macrophages were then treated with a mixed-oxysterol treatment (7-ketocholesterol and 7beta-hydroxycholesterol) for 24 hours. The mixed-oxysterol treatment was mixed to a ratio that represents the cytotoxic oxysterol content of human atherosclerotic plaque. Control and treated macrophages were analysed using both 2-DE with peptide mass-fingerprinting and tandem-mass spectrometry.

2017-03-15 | PXD004304 | Pride

Expression of oxysterol pathway genes in estrogen positive breast carcinomas-second phase

Project description:Metabolism of anticancer drugs markedly affects their antitumor effects. The major goal of our study was to investigate associations of gene expression of enzymes metabolizing taxanes and/or anthracyclines with therapy response and survival of breast carcinoma patients The present study investigated transcript levels of key modulators of oxysterol signaling pathway, including oxysterol receptors, metabolic enzymes and transporters in the group of hormone-receptor positive breast carcinoma patients to evaluated potential clinical significance of these genes.

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Oral Glucose Mobilizes Triglyceride Stores From the Human Intestine.

Project description:BACKGROUND & AIMS:The small intestine regulates plasma triglyceride (TG) concentration. Within enterocytes, dietary TGs are packaged into chylomicrons (CMs) for secretion or stored temporarily in cytoplasmic lipid droplets (CLDs) until further mobilization. We and others have shown that oral and intravenous glucose enhances CM particle secretion in human beings, however, the mechanisms through which this occurs are incompletely understood. METHODS:Two separate cohorts of participants ingested a high-fat liquid meal and, 5 hours later, were assigned randomly to ingest either a glucose solution or an equivalent volume of water. In 1 group (N = 6), plasma and lipoprotein TG responses were assessed in a randomized cross-over study. In a separate group (N = 24), duodenal biopsy specimens were obtained 1 hour after ingestion of glucose or water. Ultrastructural and proteomic analyses were performed on duodenal biopsy specimens. RESULTS:Compared with water, glucose ingestion increased circulating TGs within 30 minutes, mainly in the CM fraction. It decreased the total number of CLDs and the proportion of large-sized CLDs within enterocytes. We identified 2919 proteins in human duodenal tissue, 270 of which are related to lipid metabolism and 134 of which were differentially present in response to glucose compared with water ingestion. CONCLUSIONS:Oral glucose mobilizes TGs stored within enterocyte CLDs to provide substrate for CM synthesis and secretion. Future studies elucidating the underlying signaling pathways may provide mechanistic insights that lead to the development of novel therapeutics for the treatment of hypertriglyceridemia.

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Expression of oxysterol pathway genes in estrogen positive breast carcinomas-first phase

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