Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner
Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signalling in atherosclerosis.Here, we report that male mice with m...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 2024
|
| In: |
Cardiovascular research
Year: 2024, Jahrgang: 120, Heft: 12, Pages: 1411-1426 |
| ISSN: | 1755-3245 |
| DOI: | 10.1093/cvr/cvae125 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1093/cvr/cvae125
|
| Verfasserangaben: | Yong Wang, Guo Li, Bingni Chen, George Shakir, Mario Volz, Emiel P C van der Vorst, Sanne L Maas, Martina Geiger, Carolin Jethwa, Alexander Bartelt, Zhaolong Li, Justus Wettich, Nadja Sachs, Lars Maegdefessel, Maliheh Nazari Jahantigh, Michael Hristov, Michael Lacy, Beat Lutz, Christian Weber, Stephan Herzig, Raquel Guillamat Prats, and Sabine Steffens |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1933384492 | ||
| 003 | DE-627 | ||
| 005 | 20250911225506.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250818s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/cvr/cvae125 |2 doi | |
| 035 | |a (DE-627)1933384492 | ||
| 035 | |a (DE-599)KXP1933384492 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Wang, Yong |e VerfasserIn |0 (DE-588)1374129194 |0 (DE-627)1933385200 |4 aut | |
| 245 | 1 | 0 | |a Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner |c Yong Wang, Guo Li, Bingni Chen, George Shakir, Mario Volz, Emiel P C van der Vorst, Sanne L Maas, Martina Geiger, Carolin Jethwa, Alexander Bartelt, Zhaolong Li, Justus Wettich, Nadja Sachs, Lars Maegdefessel, Maliheh Nazari Jahantigh, Michael Hristov, Michael Lacy, Beat Lutz, Christian Weber, Stephan Herzig, Raquel Guillamat Prats, and Sabine Steffens |
| 264 | 1 | |c August 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 16 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Veröffentlicht: 5. Juni 2024, Korrektur und Schriftsatz: 9. August 2024 | ||
| 500 | |a Gesehen am 18.08.2025 | ||
| 520 | |a Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signalling in atherosclerosis.Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1-deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on oestrogen receptor (ER)α-oestradiol signalling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing, and mitochondrial respiration among the key processes affected by CB1 signalling, which was supported by metabolic flux assays. Chronic administration of the peripherally restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism, and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology.Impaired macrophage CB1 signalling is atheroprotective by limiting their arterial recruitment, proliferation, and inflammatory reprogramming in male mice. The importance of macrophage CB1 signalling appears to be sex-dependent. | ||
| 700 | 1 | |a Li, Guo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chen, Bingni |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shakir, George |e VerfasserIn |4 aut | |
| 700 | 1 | |a Volz, Mario |e VerfasserIn |4 aut | |
| 700 | 1 | |8 1\p |a Vorst, Emiel P. C. van der |d 1987- |e VerfasserIn |0 (DE-588)129638893X |0 (DE-627)1852830549 |4 aut | |
| 700 | 1 | |a Maas, Sanne L |e VerfasserIn |4 aut | |
| 700 | 1 | |a Geiger, Martina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jethwa, Carolin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bartelt, Alexander |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Zhaolong |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wettich, Justus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sachs, Nadja |e VerfasserIn |4 aut | |
| 700 | 1 | |a Maegdefessel, Lars |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nazari Jahantigh, Maliheh |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hristov, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lacy, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lutz, Beat |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weber, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herzig, Stephan |d 1969- |e VerfasserIn |0 (DE-588)12146623X |0 (DE-627)705470857 |0 (DE-576)292725949 |4 aut | |
| 700 | 1 | |a Guillamat Prats, Raquel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Steffens, Sabine |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cardiovascular research |d Oxford : Oxford University Press, 1967 |g 120(2024), 12 vom: Aug., Seite 1411-1426 |h Online-Ressource |w (DE-627)306654393 |w (DE-600)1499917-1 |w (DE-576)081984685 |x 1755-3245 |7 nnas |a Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner |
| 773 | 1 | 8 | |g volume:120 |g year:2024 |g number:12 |g month:08 |g pages:1411-1426 |g extent:16 |a Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner |
| 856 | 4 | 0 | |u https://doi.org/10.1093/cvr/cvae125 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20250901 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20250818 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 12146623X |a Herzig, Stephan |m 12146623X:Herzig, Stephan |d 50000 |e 50000PH12146623X |k 0/50000/ |p 20 | ||
| 999 | |a KXP-PPN1933384492 |e 4758658730 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title":"Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner","title_sort":"Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner"}],"physDesc":[{"noteIll":"Illustrationen","extent":"16 S."}],"relHost":[{"title":[{"title_sort":"Cardiovascular research","title":"Cardiovascular research"}],"part":{"pages":"1411-1426","issue":"12","text":"120(2024), 12 vom: Aug., Seite 1411-1426","extent":"16","volume":"120","year":"2024"},"recId":"306654393","pubHistory":["1.1967 -"],"note":["Gesehen am 01.12.2020"],"type":{"bibl":"periodical","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"1967","publisher":"Oxford University Press ; Elsevier Science","publisherPlace":"Oxford ; Amsterdam [u.a.]","dateIssuedDisp":"1967-"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1755-3245"],"eki":["306654393"],"zdb":["1499917-1"]},"disp":"Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent mannerCardiovascular research","language":["eng"]}],"origin":[{"dateIssuedDisp":"August 2024","dateIssuedKey":"2024"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Veröffentlicht: 5. Juni 2024, Korrektur und Schriftsatz: 9. August 2024","Gesehen am 18.08.2025"],"name":{"displayForm":["Yong Wang, Guo Li, Bingni Chen, George Shakir, Mario Volz, Emiel P C van der Vorst, Sanne L Maas, Martina Geiger, Carolin Jethwa, Alexander Bartelt, Zhaolong Li, Justus Wettich, Nadja Sachs, Lars Maegdefessel, Maliheh Nazari Jahantigh, Michael Hristov, Michael Lacy, Beat Lutz, Christian Weber, Stephan Herzig, Raquel Guillamat Prats, and Sabine Steffens"]},"recId":"1933384492","person":[{"given":"Yong","roleDisplay":"VerfasserIn","display":"Wang, Yong","family":"Wang","role":"aut"},{"roleDisplay":"VerfasserIn","given":"Guo","display":"Li, Guo","family":"Li","role":"aut"},{"display":"Chen, Bingni","given":"Bingni","roleDisplay":"VerfasserIn","role":"aut","family":"Chen"},{"role":"aut","family":"Shakir","display":"Shakir, George","given":"George","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","given":"Mario","display":"Volz, Mario","family":"Volz","role":"aut"},{"role":"aut","family":"Vorst","display":"Vorst, Emiel P. C. van der","given":"Emiel P. C. van der","roleDisplay":"VerfasserIn"},{"display":"Maas, Sanne L","given":"Sanne L","roleDisplay":"VerfasserIn","role":"aut","family":"Maas"},{"role":"aut","family":"Geiger","display":"Geiger, Martina","given":"Martina","roleDisplay":"VerfasserIn"},{"role":"aut","family":"Jethwa","display":"Jethwa, Carolin","roleDisplay":"VerfasserIn","given":"Carolin"},{"family":"Bartelt","role":"aut","roleDisplay":"VerfasserIn","given":"Alexander","display":"Bartelt, Alexander"},{"role":"aut","family":"Li","display":"Li, Zhaolong","given":"Zhaolong","roleDisplay":"VerfasserIn"},{"display":"Wettich, Justus","roleDisplay":"VerfasserIn","given":"Justus","role":"aut","family":"Wettich"},{"display":"Sachs, Nadja","given":"Nadja","roleDisplay":"VerfasserIn","role":"aut","family":"Sachs"},{"display":"Maegdefessel, Lars","given":"Lars","roleDisplay":"VerfasserIn","role":"aut","family":"Maegdefessel"},{"display":"Nazari Jahantigh, Maliheh","roleDisplay":"VerfasserIn","given":"Maliheh","role":"aut","family":"Nazari Jahantigh"},{"family":"Hristov","role":"aut","roleDisplay":"VerfasserIn","given":"Michael","display":"Hristov, Michael"},{"display":"Lacy, Michael","given":"Michael","roleDisplay":"VerfasserIn","role":"aut","family":"Lacy"},{"family":"Lutz","role":"aut","roleDisplay":"VerfasserIn","given":"Beat","display":"Lutz, Beat"},{"family":"Weber","role":"aut","roleDisplay":"VerfasserIn","given":"Christian","display":"Weber, Christian"},{"given":"Stephan","roleDisplay":"VerfasserIn","display":"Herzig, Stephan","family":"Herzig","role":"aut"},{"display":"Guillamat Prats, Raquel","given":"Raquel","roleDisplay":"VerfasserIn","role":"aut","family":"Guillamat Prats"},{"family":"Steffens","role":"aut","roleDisplay":"VerfasserIn","given":"Sabine","display":"Steffens, Sabine"}],"id":{"eki":["1933384492"],"doi":["10.1093/cvr/cvae125"]},"language":["eng"]} | ||
| SRT | |a WANGYONGLIMYELOIDCAN2024 | ||