Summary
Circulating plasma microvesicles (PMVs) and their microRNA content are involved in
the development of atherosclerosis and could serve as biomarkers for cardiovascular
disease (CVD) progression. However, little is known on how smoking influences the
levels of PMVs and microRNA signatures in vivo. Therefore, we aimed to investigate the effects of smoking on circulating PMV levels
and CVD-related PMV-derived microRNAs in young, healthy smokers. Twenty young (10
female, 10 male; 25 ± 4 years) healthy smokers (16 ± 6 cigarettes per day for 8 ±
4 years) and age- and sex-matched controls were included in this study. While complete
blood count revealed no differences between both groups, smoking significantly enhanced
intracellular reactive oxygen species in platelets and leukocytes as well as platelet-leukocyte
aggregate formation. Total circulating PMV counts were significantly reduced in smokers,
which could be attributed to decreased platelet-derived PMVs. While the number of
endothelial PMVs remained unaffected, smoking propagated circulating leukocyte-derived
PMVs. Despite reduced total PMVs, PMV-derived microRNA-profiling of six smoker/control
pairs revealed a decrease of only a single microRNA, the major platelet-derived microRNA
miR-223. Conversely, miR-29b, a microRNA associated with aortic aneurysm and fibrosis,
and RNU6–2, a commonly used reference-RNA, were significantly up-regulated. Smoking
leads to alterations in the circulating PMV profile and changes in the PMV-derived
microRNA signature already in young, healthy adults. These changes may contribute
to the development of smoking-related cardiovascular pathologies. Moreover, these
smoking-related changes have to be considered when microRNA or PMV profiles are used
as disease-specific biomarkers.
Keywords
Blood cells - cardiovascular diseases - cell-derived microvesicles - microRNA - smoking