Dataset Information

RNA-Seq of the liver of hypercholesterolemic mice treated by either ticagrelor, clopidogrel, or control.

ABSTRACT: RNA-Seq of the liver of hypercholesterolemic mice treated by either ticagrelor, clopidogrel, or control.

PROVIDER: PRJEB32991 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	ERR3367700_1.fastq.gz	Fastqsanger.gz
	ERR3367700_2.fastq.gz	Fastqsanger.gz
	ERR3367701_1.fastq.gz	Fastqsanger.gz
	ERR3367701_2.fastq.gz	Fastqsanger.gz
	ERR3367702_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 18

Similar Datasets

Project description:Atherosclerosis-associated vascular disease is the leading cause of death worldwide. Clinical and experimental data demonstrated that circulating monocytes internalize plasma lipoproteins and become lipid-laden foamy cells in hypercholesterolemic subjects. This study was designed to identify the endocytic mechanisms responsible for foamy monocyte formation, perform functional and transcriptomic analysis of foamy and non-foamy monocytes, and characterize specific monocyte subsets in the circulation from normocholesterolemic controls and hypercholesterolemic patients. The presence of foamy monocytes was confirmed in hypercholesterolemic mice and humans via flow cytometry analysis. High resolution scanning electron microscopy (SEM) and quantification of FITC/TRITC-dextran internalization demonstrated macropinocytosis stimulation in human (THP-1) and wild type murine monocytes in vitro. Stimulation of macropinocytosis induced foamy monocyte formation in the presence of unmodified, native LDL (nLDL) and oxidized LDL (ox-LDL) in vitro. Genetic blockade of macropinocytosis (LysMCre+ Nhe1f/f) inhibited foamy monocyte formation in hypercholesterolemic mice in vivo and attenuated monocyte adhesion to atherosclerotic aortas ex vivo. qRT-PCR quantified mRNA levels of major scavenger receptors (SR) in foamy and non-foamy monocytes and identified CD36 as a major SR increasing in response to lipid loading. Deletion of CD36 (Cd36-/-) inhibited foamy monocyte formation in hypercholesterolemic mice. Mechanistic studies identified NADPH oxidase 2 (Nox2)-derived superoxide (O2⋅−) as an important downstream signaling molecule stimulating macropinocytosis in monocytes. Bulk RNA-sequencing characterized transcriptional differences between non-foamy and foamy monocytes and macrophages. Flow cytometry analysis of CD14 and CD16 expression demonstrated a significant increase in intermediate monocytes in hypercholesterolemic patients compared to normocholesterolemic controls. These results provide novel insights into the mechanisms of foamy monocyte formation and potentially identify new therapeutic targets in the treatment of atherosclerosis.

Dataset Information

RNA-Seq of the liver of hypercholesterolemic mice treated by either ticagrelor, clopidogrel, or control.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets