Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation
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Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. / Wei, Tzu-Tang; Chandy, Mark; Nishiga, Masataka; Zhang, Angela; Kumar, Kaavya Krishna; Thomas, Dilip; Manhas, Amit; Rhee, Siyeon; Justesen, Johanne Marie; Chen, Ian Y; Wo, Hung-Ta; Khanamiri, Saereh; Yang, Johnson Y; Seidl, Frederick J.; Burns, Noah Z.; Liu, Chun; Sayed, Nazish; Shie, Jiun-Jie; Yeh, Chih-Fan; Yang, Kai-Chien; Lau, Edward; Lynch, Kara L; Rivas, Manuel; Kobilka, Brian K; Wu, Joseph C.
In: Cell, Vol. 185, No. 10, 2022, p. 1676-1693.e23.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation
AU - Wei, Tzu-Tang
AU - Chandy, Mark
AU - Nishiga, Masataka
AU - Zhang, Angela
AU - Kumar, Kaavya Krishna
AU - Thomas, Dilip
AU - Manhas, Amit
AU - Rhee, Siyeon
AU - Justesen, Johanne Marie
AU - Chen, Ian Y
AU - Wo, Hung-Ta
AU - Khanamiri, Saereh
AU - Yang, Johnson Y
AU - Seidl, Frederick J.
AU - Burns, Noah Z.
AU - Liu, Chun
AU - Sayed, Nazish
AU - Shie, Jiun-Jie
AU - Yeh, Chih-Fan
AU - Yang, Kai-Chien
AU - Lau, Edward
AU - Lynch, Kara L
AU - Rivas, Manuel
AU - Kobilka, Brian K
AU - Wu, Joseph C
N1 - Copyright © 2022 Elsevier Inc. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ 9-tetrahydrocannabinol (Δ 9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ 9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ 9-THC. In mice, genistein blocked Δ 9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ 9-THC-induced atherosclerosis.
AB - Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ 9-tetrahydrocannabinol (Δ 9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ 9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ 9-THC. In mice, genistein blocked Δ 9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ 9-THC-induced atherosclerosis.
U2 - 10.1016/j.cell.2022.04.005
DO - 10.1016/j.cell.2022.04.005
M3 - Journal article
C2 - 35489334
VL - 185
SP - 1676-1693.e23
JO - Cell
JF - Cell
SN - 0092-8674
IS - 10
ER -
ID: 306105978