Endothelial-derived extracellular vesicles associated with electronic cigarette use impair cerebral microvascular cell function

Hannah L. Cardenas, Nicholas G. Evanoff, Hannah K. Fandl, Auburn R. Berry, Kendra N. Wegerson, Emily I. Ostrander, Jared J. Greiner, Sheena R. Dufresne, Michael Kotlyar, Donald R. Dengel, Christopher A. DeSouza, Vinicius P. Garcia

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The aim of this study was to determine the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from e-cigarette users on human cerebral microvascular endothelial cells (hCMECs) nitric oxide (NO) and endothelin (ET)-1 production and tissue-type plasminogen activator (t-PA) release. Circulating EMVs (CD144-PE) were isolated (flow cytometry) from 27 young adults (19–25 yr): 10 nonsmokers (6 M/4 F), 10 e-cigarette users (6 M/4 F), and 7 tobacco cigarette smokers (4 M/3 F). hCMECs were cultured and treated with isolated EMVs for 24 h. EMVs from e-cigarette users and cigarette smokers induced significantly higher expression of p-eNOS (Thr495; 28.4 ± 4.6 vs. 29.1 ± 2.8 vs. 22.9 ± 3.8 AU), Big ET-1 (138.8 ± 19.0 vs. 141.7 ± 19.1 vs. 90.3 ± 18.8 AU) and endothelin converting enzyme (107.6 ± 10.1 and 113.5 ± 11.8 vs. 86.5 ± 13.2 AU), and significantly lower expression of p-eNOS (Ser1177; 7.4 ± 1.7 vs. 6.5 ± 0.5 vs. 9.7 ± 1.6 AU) in hCMECs than EMVs from nonsmokers. NO production was significantly lower and ET-1 production was significantly higher in hCMECs treated with EMVs from e-cigarette (5.7 ± 0.8 lmol/L; 33.1 ± 2.9 pg/mL) and cigarette smokers (6.3 ± 0.7 lmol/L; 32.1 ± 3.9 pg/mL) than EMVs from nonsmokers (7.6 ± 1.2 lmol/L; 27.9 ± 3.1 pg/mL). t-PA release in response to thrombin was significantly lower in hCMECs treated with EMVs from e-cigarette users (from 38.8 ± 6.3 to 37.4 ± 8.3 pg/mL) and cigarette smokers (31.5 ± 5.5 to 34.6 ± 8.4 pg/mL) than EMVs from nonsmokers (38.9 ± 4.3 to 48.4 ± 7.9 pg/mL). There were no significant differences in NO, ET-1, or t-PA protein expression or production in hCMECs treated with EMVs from e-cigarette users and smokers. Circulating EMVs associated with e-cigarette use adversely affects brain microvascular endothelial cells and may contribute to reported cerebrovascular dysfunction with e-cigarette use.

Original languageEnglish (US)
Pages (from-to)271-278
Number of pages8
JournalJournal of applied physiology
Volume135
Issue number2
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 American Physiological Society. All rights reserved.

Keywords

  • e-cigarette
  • endothelial cells
  • endothelial microvesicles
  • smoking

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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