Abstract Body (Do not enter title and authors here): Background: Inhaled cannabis has been associated with increased risk of acute coronary events, yet the mechanisms remain unknown.
Hypothesis. Using a novel ex vivo mechanistic atherogenesis assay, the purpose of this translational study was to test the hypothesis that combusted cannabis use increases two early steps in atherogenesis, monocyte transendothelial migration (MTEM) and monocyte-derived foam cell formation (MDFCF), in people who use combusted cannabis, and that these changes are further increased in people who co-use combusted cannabis with nicotine electronic cigarettes (nECIGs), the tobacco product of choice in young people.
Methods: In a cross-sectional study, using PBMCs and plasma from healthy adults (21-30 y) who chronically 1) use inhaled combusted cannabis, 2) co-use combusted cannabis and nECIGs, and 3) non-using controls, proatherogenic monocyte factors were measured using our ex vivo atherogenesis assay (Fig 1A) and compared amongst the 3 groups. Outcomes were 1) MTEM (% of blood monocytes that undergo transendothelial migration through a collagen gel), and 2) MDFCF as determined by flow cytometry and 3) the median fluorescence intensity (MDFCF-MFI) of the lipid staining fluorochrome BODIPY in monocytes.
Results: A total of 134 participants were enrolled (combusted cannabis use=59, combusted cannabis/nECIG co-use=26, control=49). The demographics of the groups did not differ. The MTEM was significantly greater in people who use cannabis (27.8+4.4%, p<0.00001, mean±SD) or co-use cannabis/nECIG (33.2+7.8%, p<0.0001) vs controls (24.8 +2.8%) and tended to be greater in people who co-use cannabis/nECIG vs cannabis alone (p=0.056, Fig 1B). Similarly, MDFCF and MDFCF-MFI were greater in people who use cannabis (35.8 +6.5%,1155.0 +159.6 u, respectively) or co-use cannabis/nECIG (44.7+10.0%, 1464.2 +253.1 u) vs controls (25.8+8.6%, 967.2+170.2 u; p<0.00001 for all) and were significantly greater in people who co-use cannabis/nECIG vs cannabis alone (p=0.03; Figs 1C &1D).
Conclusions. Chronic use of combusted cannabis is associated with higher monocyte transendothelial migration and monocyte-derived foam cell formation, two early instigators of atherogenesis, in a novel ex vivo atherogenesis assay. The changes are further increased in people who co-use combusted cannabis with nicotine electronic cigarettes. These findings provide mechanistic insights into the observation that cannabis use is associated with increased risk of myocardial infarction.