β-carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12643170.fastq.gz | Fastqsanger.gz | |||
| SRR12643171.fastq.gz | Fastqsanger.gz | |||
| SRR12643172.fastq.gz | Fastqsanger.gz | |||
| SRR12643173.fastq.gz | Fastqsanger.gz | |||
| SRR12643174.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of cardiovascular diseases (CVDs), and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affect atherosclerosis progression in the atheroprone low-density lipoprotein receptor (LDLR) - deficient mice. In comparison to control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and plasma cholesterol levels (P = 0.0003). These changes were absent in Ldlr-/-/Bco1-/- mice, despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
2020-11-12 | GSE157972 | GEO
Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr-/- /Bco1-/- mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
| S-EPMC7604725 | biostudies-literature
Project description:Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3' untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet-fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe(-/-) mice. Furthermore, inhibition of hepatic miR-30c by anti-miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
| S-EPMC4121125 | biostudies-literature
Project description:Klebsiella pneumoniae strain:Respiratory secretion | isolate:Respiratory secretion Genome sequencing
| PRJNA1134426 | ENA
Project description:Human uterine secretion Raw sequence reads
| PRJNA705499 | ENA
Project description:Vaginal secretion sample Raw sequence reads
| PRJNA1179695 | ENA
Project description:BackgroundAtherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids and leukocytes within the arterial wall. By studying the aortic transcriptome of atherosclerosis-prone apolipoprotein E (ApoE-/-) mice, we aimed to identify novel players in the progression of atherosclerosis.MethodsRNA-Seq analysis was performed on aortas from ApoE-/- and wild-type mice. AnxA8 expression was assessed in human and mice atherosclerotic tissue and healthy aorta. ApoE-/- mice lacking systemic AnxA8 (ApoE-/-AnxA8-/-) were generated to assess the effect of AnxA8 deficiency on atherosclerosis. Bone marrow transplantation (BMT) was also performed to generate ApoE-/- lacking AnxA8 specifically in bone marrow-derived cells. Endothelial-specific AnxA8 silencing in vivo was performed in ApoE-/- mice. The functional role of AnxA8 was analysed in cultured murine cells.ResultsRNA-Seq unveiled AnxA8 as one of the most significantly upregulated genes in atherosclerotic aortas of ApoE-/- compared to wild-type mice. Moreover, AnxA8 was upregulated in human atherosclerotic plaques. Germline deletion of AnxA8 decreased the atherosclerotic burden, the size and volume of atherosclerotic plaques in the aortic root. Plaques of ApoE-/-AnxA8-/- were characterized by lower lipid and inflammatory content, smaller necrotic core, thicker fibrous cap and less apoptosis compared with those in ApoE-/-AnxA8+/+. BMT showed that hematopoietic AnxA8 deficiency had no effect on atherosclerotic progression. Oxidized low-density lipoprotein (ox-LDL) increased AnxA8 expression in murine aortic endothelial cells (MAECs). In vitro experiments revealed that AnxA8 deficiency in MAECs suppressed P/E-selectin and CD31 expression and secretion induced by ox-LDL with a concomitant reduction in platelet and leukocyte adhesion. Intravital microscopy confirmed the reduction in leukocyte and platelet adhesion in ApoE-/-AnxA8-/- mice. Finally, endothelial-specific silencing of AnxA8 decreased atherosclerosis progression.ConclusionOur findings demonstrate that AnxA8 promotes the progression of atherosclerosis by modulating endothelial-leukocyte interactions. Interventions capable of reducing AnxA8 expression in endothelial cells may delay atherosclerotic plaque progression.Key pointsThis study shows that AnxA8 is upregulated in aorta of atheroprone mice and in human atherosclerotic plaques. Germline AnxA8 deficiency reduces platelet and leukocyte recruitment to activated endothelium as well as atherosclerotic burden, plaque size, and macrophage accumulation in mice. AnxA8 regulates oxLDL-induced adhesion molecules expression in aortic endothelial cells. Our data strongly suggest that AnxA8 promotes disease progression through regulation of adhesion and influx of immune cells to the intima. Endothelial specific silencing of AnxA8 reduced atherosclerosis progression. Therapeutic interventions to reduce AnxA8 expression may delay atherosclerosis progression.
| S-EPMC11748212 | biostudies-literature
Project description:FloChIP's decreasing cell number data obtained in multiplexing mode
| PRJEB28205 | ENA
Project description:Oridonin delays aging through AKT signaling pathway
| PRJNA784535 | ENA