Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. Cell 2022 May 12;185(10):1676-1693.e23
Date
05/01/2022Pubmed ID
35489334Pubmed Central ID
PMC9400797DOI
10.1016/j.cell.2022.04.005Scopus ID
2-s2.0-85129930623 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
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.
Author List
Wei TT, Chandy M, Nishiga M, Zhang A, Kumar KK, Thomas D, Manhas A, Rhee S, Justesen JM, Chen IY, Wo HT, Khanamiri S, Yang JY, Seidl FJ, Burns NZ, Liu C, Sayed N, Shie JJ, Yeh CF, Yang KC, Lau E, Lynch KL, Rivas M, Kobilka BK, Wu JCAuthor
Chun Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnalgesicsAnimals
Cannabinoid Receptor Agonists
Cannabis
Cardiovascular Diseases
Dronabinol
Endothelial Cells
Genistein
Hallucinogens
Inflammation
Mice
Receptor, Cannabinoid, CB1
Receptors, Cannabinoid
