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

Area of Science:

• Cardiovascular Research
• Endothelial Cell Biology
• Vascular Health

Background:

• E-cigarette use is rising, but its impact on vascular health remains incompletely understood.
• Endothelial cells form the inner lining of blood vessels and play a crucial role in vascular homeostasis.
• Circulating microvesicles, particularly endothelial cell-derived microvesicles (EMVs), are implicated as mediators of intercellular communication and disease processes.

Purpose of the Study:

• To investigate the effects of EMVs from e-cigarette users on human cerebral microvascular endothelial cells (hCMECs).
• To assess the impact of these EMVs on nitric oxide (NO), endothelin-1 (ET-1) production, and tissue-type plasminogen activator (t-PA) release.
• To determine if EMVs from e-cigarette users contribute to cerebrovascular dysfunction.

Main Methods:

• Isolation of circulating EMVs from nonsmokers, e-cigarette users, and tobacco cigarette smokers using flow cytometry (CD144-PE).
• Culture of hCMECs and treatment with isolated EMVs for 24 hours.
• Measurement of key markers including p-eNOS (Thr495 and Ser1177), Big ET-1, endothelin converting enzyme, NO production, ET-1 production, and thrombin-induced t-PA release.

Main Results:

• EMVs from e-cigarette users and smokers significantly increased p-eNOS (Thr495) and Big ET-1 expression, and endothelin converting enzyme levels in hCMECs compared to nonsmokers.
• EMVs from e-cigarette users and smokers significantly decreased p-eNOS (Ser1177) expression.
• hCMECs treated with EMVs from e-cigarette users and smokers showed significantly lower NO production and higher ET-1 production.
• EMVs from e-cigarette users and smokers significantly reduced t-PA release in response to thrombin.

Conclusions:

• Circulating EMVs derived from e-cigarette users adversely affect human cerebral microvascular endothelial cells.
• These EMVs alter critical pathways regulating vascular function, including NO and ET-1 production, and t-PA release.
• EMVs may serve as a key mediator linking e-cigarette use to an increased risk of cerebrovascular dysfunction and events.