Abstract 5565: Smoking-Induced Long-lasting Modifications Through a Monoamine Oxidase Epigenetic Regulation
Objectives: Smoking is a major cardiovascular risk factor. We postulated that serotonin, released from activated platelets, could be involved in smoking-induced vascular modifications.
Patients & Methods: We studied 115 men with no history of cardiovascular disease and no diabetes, distributed as smokers (S), former smokers (FS) who had stopped smoking for a mean of 13 years, and never smokers (NS). There was no difference in age, BMI, blood pressure or lipid status between the 3 groups. Serotonin, monoaminoxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA) - the serotonin/MAO catabolite - in plasma samples. Genomic sequencing of the MAO gene promoter was performed on peripheral blood monocytic cells (PBMC).
Results: Both platelet serotonin and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Unexpectedly, the platelet serotonin content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme amount found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B a study of the methylation of its gene promoter in a supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity.
Conclusions: This is the first report that smoking induces an epigenetic modification lasting over ten years after quitting. A better understanding of the epigenome may help to further elucidate the development of smoking-induced vascular complications. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent serotonin catabolism is also involved in addiction and lung cancer.