|
| Status |
Public on Apr 04, 2020 |
| Title |
Anti-inflammatory effects of HDL in macrophages predominate over pro-inflammatory effects in atherosclerotic plaques |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
HDL infusion reduces atherosclerosis in animal models and is being evaluated as a treatment in humans. While some studies have shown anti-inflammatory effects of HDL in macrophages, others have reported pro-inflammatory effects and there is no consensus on underlying mechanisms. Transcriptional profiling reveals that HDL-mediated cholesterol efflux leads to both pro- and anti-inflammatory effects in LPS-stimulated macrophages. While early anti-inflammatory effects reflect reduced TLR4 levels, late anti-inflammatory effects are due to reduced interferon receptor signaling. Pro-inflammatory effects occur late and are ER stress responses mediated by IRE1a/ASK1/p38 MAPK signaling under conditions of marked cholesterol depletion. rHDL infusions in hypercholesterolemic atherosclerotic mice produced moderate anti-inflammatory effects in lesional macrophages without pro-inflammatory gene expression changes suggesting a beneficial therapeutic effect of HDL in vivo.
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| |
|
| Overall design |
mRNA profiling of BMDM treated with rHDL
|
| |
|
| Contributor(s) |
Thomas DG, Tall A |
| Citation(s) |
31578081 |
| |
| Submission date |
Apr 04, 2019 |
| Last update date |
Apr 10, 2020 |
| Contact name |
David G Thomas |
| Organization name |
Columbia University
|
| Department |
Medicine
|
| Street address |
630 W 168th St P&S 8-401
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA530992 |
| SRA |
SRP190876 |
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