TY - JOUR
T1 - Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake
AU - Chen, Bingni
AU - Prabhu, Aishvaryaa
AU - Li, Guo
AU - Kaltenbach, Anna
AU - Wang, Yong
AU - Shakir, George
AU - Natarelli, Lucia
AU - Megens, Remco
AU - Jansen, Yvonne
AU - Ramanathan, Srishti
AU - Geiger, Martina
AU - Faussner, Alexander
AU - Hristov, Michael
AU - Richter, Daniel
AU - Di, Xinyu
AU - van der Stelt, Mario
AU - Triantafyllidou, Vasiliki
AU - Li, Zhaolong
AU - Sachs, Nadja
AU - Paloschi, Valentina
AU - Maegdefessel, Lars
AU - Hofmann, Susanna M.
AU - Schifferer, Martina
AU - Simons, Mikael
AU - Weber, Christian
AU - Santovito, Donato
AU - Herzig, Stephan
AU - Guillamat Prats, Raquel
AU - Steffens, Sabine
N1 - Funding Information:
The authors received funds from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation,\u00A0STE1053/6-1, STE1053/8-1 to S.S., CRC1123, project number\u00A0238187445 to S.S., L.N., R.M., L.M., M.N.J., S.M.H, C.W., D.S., and S.H.) and CRC1744,\u00A0project number 548585053 to S.S. and M.S., the German Ministry of Research and Education (DZHK FKZ 81Z0600205 to S.S. and 81Z0600103 to S.H.), the LMU Medical Faculty F\u00F6FoLe program (1061 to R.G.P.), and the Chinese Scholar Council (CSC 201908440429 to B.C., 201908080123 to Y.W., and 202006380058 to G.L.). Open Access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12/1
Y1 - 2026/12/1
N2 - Peripheral cannabinoid CB1 receptor antagonists that lack central nervous system effects are emerging as promising therapies for metabolic disease, yet the role of endothelial CB1 signaling in atherosclerosis remains unclear. Here, we show that endothelial CB1 is expressed in human atherosclerotic plaques, is induced by oscillatory shear stress in atheroprone flow regions, and promotes vascular inflammation, permeability and lipid uptake. Endothelial-specific Cnr1 deletion or peripheral CB1 antagonism in mice attenuates atherosclerosis, reduces endothelial caveolae–dependent low-density lipoprotein uptake by downregulating caveolin-1 and ALK1 expression, and improves metabolic parameters in brown and white adipose tissue and the liver. The anti-atherogenic and metabolic effects are more pronounced in females, which is possibly linked to estrogen signaling. These findings identify endothelial CB1 as a proatherogenic, sex-biased regulator of vascular lipid transport and plaque development and associated metabolic dysfunction.
AB - Peripheral cannabinoid CB1 receptor antagonists that lack central nervous system effects are emerging as promising therapies for metabolic disease, yet the role of endothelial CB1 signaling in atherosclerosis remains unclear. Here, we show that endothelial CB1 is expressed in human atherosclerotic plaques, is induced by oscillatory shear stress in atheroprone flow regions, and promotes vascular inflammation, permeability and lipid uptake. Endothelial-specific Cnr1 deletion or peripheral CB1 antagonism in mice attenuates atherosclerosis, reduces endothelial caveolae–dependent low-density lipoprotein uptake by downregulating caveolin-1 and ALK1 expression, and improves metabolic parameters in brown and white adipose tissue and the liver. The anti-atherogenic and metabolic effects are more pronounced in females, which is possibly linked to estrogen signaling. These findings identify endothelial CB1 as a proatherogenic, sex-biased regulator of vascular lipid transport and plaque development and associated metabolic dysfunction.
U2 - 10.1038/s41467-026-75214-2
DO - 10.1038/s41467-026-75214-2
M3 - Article
SN - 2041-1723
VL - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5939
ER -