Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation

Cell. 2022 Apr 29:S0092-8674(22)00443-3. doi: 10.1016/j.cell.2022.04.005. Online ahead of print.ABSTRACTEpidemiological 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.PMID:35489334 | DOI:10.1016/j.cell.2022.04.005

Source: Atherosclerosis - April 30, 2022 Category: Cardiology 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 Shi Source Type: research