| Title: | Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation |
| Journal: | Cell |
| Published: | 29 Apr 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35489334/ |
| DOI: | https://doi.org/10.1016/j.cell.2022.04.005 |
| Citations: | 57 (44 in last 2 years) as of 8 Aug 2024 |
Publication 12394
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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.</p>
13 Keywords
- Analgesics
- Animals
- Cannabinoid Receptor Agonists
- Cannabis
- Cardiovascular Diseases
- Dronabinol
- Endothelial Cells
- Genistein
- Hallucinogens
- Inflammation
- Mice
- Receptor, Cannabinoid, CB1
- Receptors, Cannabinoid
25 Authors
- Tzu-Tang Wei
- Mark Chandy
- Masataka Nishiga
- Angela Zhang
- Kaavya Krishna Kumar
- Dilip Thomas
- Amit Manhas
- Siyeon Rhee
- Johanne Marie Justesen
- Ian Y Chen
- Hung-Ta Wo
- Saereh Khanamiri
- Johnson Y Yang
- Frederick J Seidl
- Noah Z Burns
- Chun Liu
- Nazish Sayed
- Jiun-Jie Shie
- Chih-Fan Yeh
- Kai-Chien Yang
- Edward Lau
- Kara L Lynch
- Manuel Rivas
- Brian K Kobilka
- Joseph C Wu
Enabling scientific discoveries that improve human health