Dataset Information

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

ABSTRACT: Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ⁹-tetrahydrocannabinol (Δ⁹-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 Δ⁹-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 Δ⁹-THC. In mice, genistein blocked Δ⁹-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 Δ⁹-THC-induced atherosclerosis.

SUBMITTER: Wei TT

PROVIDER: S-EPMC9400797 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Wei Tzu-Tang TT Chandy Mark M Nishiga Masataka M Zhang Angela A Kumar Kaavya Krishna KK Thomas Dilip D Manhas Amit A Rhee Siyeon S Justesen Johanne Marie JM Chen Ian Y IY Wo Hung-Ta HT Khanamiri Saereh S Yang Johnson Y JY Seidl Frederick J FJ Burns Noah Z NZ Liu Chun C Sayed Nazish N Shie Jiun-Jie JJ Yeh Chih-Fan CF Yang Kai-Chien KC Lau Edward E Lynch Kara L KL Rivas Manuel M Kobilka Brian K BK Wu Joseph C JC

Cell 20220429 10

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-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 ...[more]

PMID: 35489334

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Dataset Information

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

Publications

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation.

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