Cardiovascular research, 2022-01, Vol.118 (1), p.156-168
2022
Details
- Autor(en) / Beteiligte
- Titel
- Deficiency of inactive rhomboid protein 2 (iRhom2) attenuates diet-induced hyperlipidaemia and early atherogenesis
- Ist Teil von
- Cardiovascular research, 2022-01, Vol.118 (1), p.156-168
- Ort / Verlag
- England: Oxford University Press
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- Oxford Journals 2020 Medicine
- Beschreibungen/Notizen
- Abstract Aims Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and anti-inflammatory treatment strategies are currently pursued to lower cardiovascular disease burden. Modulation of recently discovered inactive rhomboid protein 2 (iRhom2) attenuates shedding of tumour necrosis factor-alpha (TNF-α) selectively from immune cells. The present study aims at investigating the impact of iRhom2 deficiency on the development of atherosclerosis. Methods and results Low-density lipoprotein receptor (LDLR)-deficient mice with additional deficiency of iRhom2 (LDLR−/−iRhom2−/−) and control (LDLR−/−) mice were fed a Western-type diet (WD) for 8 or 20 weeks to induce early or advanced atherosclerosis. Deficiency of iRhom2 resulted in a significant decrease in the size of early atherosclerotic plaques as determined in aortic root cross-sections. LDLR−/−iRhom2−/− mice exhibited significantly lower serum levels of TNF-α and lower circulating and hepatic levels of cholesterol and triglycerides compared to LDLR−/− mice at 8 weeks of WD. Analyses of hepatic bile acid concentration and gene expression at 8 weeks of WD revealed that iRhom2 deficiency prevented WD-induced repression of hepatic bile acid synthesis in LDLR−/− mice. In contrast, at 20 weeks of WD, plaque size, plaque composition, and serum levels of TNF-α or cholesterol were not different between genotypes. Conclusion Modulation of inflammation by iRhom2 deficiency attenuated diet-induced hyperlipidaemia and early atherogenesis in LDLR−/− mice. iRhom2 deficiency did not affect diet-induced plaque burden and composition in advanced atherosclerosis in LDLR−/− mice. Graphical Abstract
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-6363eISSN: 1755-3245DOI: 10.1093/cvr/cvab041Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8932158
- Format
- –
- Schlagworte
- Animals, Aorta - metabolism, Aorta - pathology, Aortic Diseases - blood, Aortic Diseases - genetics, Aortic Diseases - pathology, Aortic Diseases - prevention & control, Atherosclerosis - blood, Atherosclerosis - genetics, Atherosclerosis - pathology, Atherosclerosis - prevention & control, Bile Acids and Salts - metabolism, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cytokines - blood, Diet, High-Fat, Disease Models, Animal, Editor's Choice, Hyperlipidemias - blood, Hyperlipidemias - genetics, Hyperlipidemias - prevention & control, Inflammation Mediators - blood, Lipids - blood, Liver - metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes - metabolism, Original, Plaque, Atherosclerotic, Receptors, LDL - genetics, Receptors, LDL - metabolism