Bibliographic Details
| Title: |
DHCR24 inhibitor SH42 increases desmosterol without preventing atherosclerosis development in mice |
| Authors: |
Xiaoke Ge, Bram Slütter, Joost M. Lambooij, Enchen Zhou, Zhixiong Ying, Ceren Agirman, Marieke Heijink, Antoine Rimbert, Bruno Guigas, Johan Kuiper, Christoph Müller, Franz Bracher, Martin Giera, Sander Kooijman, Patrick C.N. Rensen, Yanan Wang, Milena Schönke |
| Source: |
iScience, Vol 27, Iss 6, Pp 109830- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Cardiovascular medicine, Cellular physiology, Molecular genetics, Science |
| More Details: |
Summary: The liver X receptor (LXR) is considered a therapeutic target for atherosclerosis treatment, but synthetic LXR agonists generally also cause hepatic steatosis and hypertriglyceridemia. Desmosterol, a final intermediate in cholesterol biosynthesis, has been identified as a selective LXR ligand that suppresses inflammation without inducing lipogenesis. Δ24-Dehydrocholesterol reductase (DHCR24) converts desmosterol into cholesterol, and we previously showed that the DHCR24 inhibitor SH42 increases desmosterol to activate LXR and attenuate experimental peritonitis and metabolic dysfunction-associated steatotic liver disease. Here, we aimed to evaluate the effect of SH42 on atherosclerosis development in APOE∗3-Leiden.CETP mice and low-density lipoproteins (LDL) receptor knockout mice, models for lipid- and inflammation-driven atherosclerosis, respectively. In both models, SH42 increased desmosterol without affecting plasma lipids. While reducing liver lipids in APOE∗3-Leiden.CETP mice, and regulating populations of circulating monocytes in LDL receptor knockout mice, SH42 did not attenuate atherosclerosis in either model. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2589004224010526; https://doaj.org/toc/2589-0042 |
| DOI: |
10.1016/j.isci.2024.109830 |
| Access URL: |
https://doaj.org/article/d72d912914924864b6d5ff9166b6b6a7 |
| Accession Number: |
edsdoj.72d912914924864b6d5ff9166b6b6a7 |
| Database: |
Directory of Open Access Journals |
