Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Cell |
Volume | 185 |
Issue number | 10 |
Pages (from-to) | 1676-1693.e23 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Copyright © 2022 Elsevier Inc. All rights reserved.
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400797/pdf/nihms-1820885.pdf
Accepted author manuscript
ID: 306105978