Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids.

BACKGROUND

The pathophysiological mechanisms of air pollution-induced atherosclerosis are incompletely understood. Sphingolipids serve as biological intermediates during atherosclerosis development by facilitating production of proatherogenic apoB (apolipoprotein B)-containing lipoproteins. We explored whether sphingolipids mediate the proatherogenic effects of air pollution.

METHODS

This was a prospective panel study of 110 participants (mean age 56.5 years) followed from 2013 to 2015 in Beijing, China. Targeted lipidomic analyses were used to quantify 24 sphingolipids in 579 plasma samples. The mass concentrations of ambient particulate matter ≤2.5 μm in diameter (PM) were continuously monitored by a fixed station. We evaluated the associations between sphingolipid levels and average PM concentrations 1-30 days before clinic visits using linear mixed-effects models and explored whether sphingolipids mediate PM-associated changes in the levels of proatherogenic apoB-containing lipoproteins (LDL-C [low-density lipoprotein cholesterol] and non-HDL-C [nonhigh-density lipoprotein cholesterol]) using mediation analyses.

RESULTS

We observed significant increases in the levels of non-HDL-C and fourteen sphingolipids associated with PM exposure, from short- (14 days) to medium-term (30 days) exposure time windows. The associations exhibited near-monotonic increases and peaked in 30-day time window. Increased levels of the sphingolipids, namely, sphinganine, ceramide C24:0, sphingomyelins C16:0/C18:0/C18:1/C20:0/C22:0/C24:0, and hexosylceramides C16:0/C18:0/C20:0/C22:0/C24:0/C24:1 significantly mediated 32%, 58%, 35% to 93%, and 23% to 86%, respectively, of the positive association between 14-day PM average and the non-HDL-C level, but not the LDL-C level. Similar mediation effects (19%-91%) of the sphingolipids were also observed in 30-day time window.

CONCLUSIONS

Our results suggest that sphingolipids may mediate the proatherogenic effects of short- and medium-term PM exposure.