Abstract

AbstractPostulating that serotonin, secreted from smoking-activated platelets, could be involved in smoking-induced vascular modifications, we studied 115 men distributed in smokers (S), former smokers (FS) and never smokers (NS). The platelet serotonin content was similar in S and NS but lower in FS. This was unexpected because the monoamine oxidase (MAO) activity, which catabolizes serotonin, was inhibited during smoking. However, the amount of platelet MAO was higher in S and FS than in NS. The persistent elevated MAO amount in FS prompted us to study the methylation of its gene promoter in an additional series of patients: it was markedly lower for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity. This smoking-induced demethylation of the MAO gene promoter, resulting in high MAO amount persisting long after quitting smoking, has cardiovascular consequences and could impact fields such as behavior, mental health, and cancer.

Highlights

  • Platelet 5-HT and plasma 5-hydroxyindole acetic acid (5-HIAA) Because, so far, most studies dealing with smoking have compared S and never smokers (NS), we initially considered only two groups, i.e. current smokers [S] and presently-non-smokers who had not smoked for at least one year on the day of blood sampling

  • We showed that the 5-HT content was significantly reduced in platelets of former smokers (FS) who had quitted smoking for a mean of 13 years

  • This smoking-induced long-lasting effect was due to demethylation of the MAOB gene promoter which resulted in a persisting high platelet monoamine oxidase (MAO)-B amount

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Summary

Introduction

The persistent elevated MAO amount in FS prompted us to study the methylation of its gene promoter in an additional series of patients: it was markedly lower for S and FS vs NS due to cigarette smoke-induced increase of nucleic acid demethylase activity. We found that smoking induced an epigenetic regulation of MAOB, i.e. a reduction of its gene promoter methylation, resulting in high MAO amounts which persist long after (over 10 years) quitting smoking.

Results
Conclusion
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