Long-term nicotine exposure induces dysfunction of mouse endothelial progenitor cells

Abstract

Endothelial progenitor cells (EPCs) have an important role in maintaining endothelial homeostasis. Previous studies reported that smoking has detrimental effects on EPCs; however, recent studies revealed that short-term nicotine exposure may benefit EPCs. As most smokers are exposed to nicotine over an extended time period, the present study aimed to investigate the long-term effects of nicotine on EPCs. Mice were administered nicotine orally for 1, 3 or 6 months. The mice exposed to nicotine for 1 month demonstrated increased EPC counts and telomerase activity and reduced cell senescence compared with control mice, consistent with previous reports. However, long-term nicotine exposure resulted in opposing effects on EPCs, causing decreased counts, functional impairment and reduced telomerase activity. Furthermore, the effects of nicotine exposure were correlated with changes in sirtuins type 1 (SIRT1) protein expression. The current study indicated that long-term nicotine exposure induces dysfunction and senescence of EPCs, which may be associated with impairment of telomerase activity through SIRT1 downregulation. The present results emphasize the necessity of smoking cessation to prevent dysfunction of EPCs.

Humoral and Cellular Patterns of Early Endothelial Progenitor Cells in Relation to the Cardiovascular Risk in Axial Spondylarthritis

“…Other CVR factors did not show any impact on colony formation or circulating EPCs, neither if compared to the controls nor if exclusively analyzed between axSpA patients. These data are not truly surprising since comparable observations have been made in the past, at least in hypertension and nicotine abuse [35, 36]. Statins have been documented to increase peripheral EPCs [37].…”

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects

“…On the other hand, the second statement, i.e., “prolonged exposure to nicotine resulted in decreased EPC number,” is an affirmation that smoking is injurious to health. As a result, the above study [172] underscores the cessation of smoking to prevent endothelial dysregulation.…”

“…It was hypothesized that the increased EPC activity was due to the antiapoptotic effect of nicotine on EPCs via activation of the nicotinic acetylcholine receptor (nAChR) [170]. However, in another study, it was postulated that nicotine activates telomerase activity through either the PI3K/AKT pathway (by increased phosphorylation of human telomerase reverse transcriptase (hTERT) [171, 172] or upregulation of sirtuin type 1 (SIRT1) protein expression [172]. Telomerase activity may be responsible for cellular senescence [173].…”

“…It was observed that short-term nicotine exposure increased the proliferative capacity of EPCs, which is consistent with the above-described studies. However, at six months, there was a marked reversal in the number, functional impairment, and telomerase activity of EPCs [172].…”

Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers

“…As discussed before, the main trigger for EPC mobilization is the endothelial expulsion of VEGF-2 and SDF-1 -two cytokines responsible for the homing of EPCs to the vascular wall [114]. Li et al demonstrated in mice that daily oral administration of nicotine caused an initial increase of EPC proliferation in vitro following one month of exposure and then a subsequent decrease of EPC proliferation at both, 3 and 6 months [170]. In addition, they also showed that these EPCs showed signs of dysfunction.…”