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Series GSE157972 Query DataSets for GSE157972
Status Public on Nov 12, 2020
Title β-carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design CD68+ cells accumulated in atherosclerotic lesions at the level of the aortic root were isolated by laser capture microdisection. Briefly, Eight-week-old male and female Ldlr-/-/Bco1-/- mice were lethally irradiated with a double dose of 550 rads (5.5 GY) from a cesium source four hours apart. Ten hours later, mice were transplanted with freshly isolated bone marrow from donor wild-type or Bco1-/- (ko) mice.
 
Contributor(s) Zhou F, Wu X, Pinos I, Abraham BM, Barrett TJ, Khodadadi-Jamayran A, von Lintig J, Fisher EA, Amengual J
Citation(s) 32963037
Submission date Sep 15, 2020
Last update date Nov 12, 2020
Contact name Alireza Khodadadi-Jamayran
Organization name New York University, NYU Langone Medical Center
Department Division of Advanced Research Technologies (DART)
Lab Applied Bioinformatics Laboratories (ABL)
Street address 550 1st Ave, MSB 304
City New York City
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM4782076 WT female Bone Marrow (BM) donor_27
GSM4782077 Bco1-/- (KO) Female BM donor_38
GSM4782078 WT female BM donor_39
Relations
BioProject PRJNA663568
SRA SRP282456

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE157972_RAW.tar 880.7 Mb (http)(custom) TAR (of BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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