Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling.
In: American Journal of Physiology: Heart & Circulatory Physiology, Jg. 322 (2022-04-01), Heft 4, S. H549- (19S.)
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Zugriff:
We recently reported a mouse model of chronic electronic cigarette (e-cig) exposure-induced cardiovascular pathology, where long-term exposure to e-cig vape (ECV) induces cardiac abnormalities, impairment of endothelial function, and systemic hypertension. Here, we delineate the underlying mechanisms of ECV-induced vascular endothelial dysfunction (VED), a central trigger of cardiovascular disease. C57/BL6 male mice were exposed to ECV generated from e-cig liquid containing 0, 6, or 24 mg/mL nicotine for 16 and 60 wk. Time-dependent elevation in blood pressure and systemic vascular resistance were observed, along with an impairment of acetylcholine-induced aortic relaxation in ECV-exposed mice, compared with airexposed control. Decreased intravascular nitric oxide (NO) levels and increased superoxide generation with elevated 3-nitrotyrosine levels in the aorta of ECV-exposed mice were observed, indicating that ECV-induced superoxide reacts with NO to generate cytotoxic peroxynitrite. Exposure increased NADPH oxidase expression, supporting its role in ECV-induced superoxide generation. Downregulation of endothelial nitric oxide synthase (eNOS) expression and Akt-dependent eNOS phosphorylation occurred in the aorta of ECV-exposed mice, indicating that exposure inhibited de novo NO synthesis. Following ECV exposure, the critical NOS cofactor tetrahydrobiopterin was decreased, with a concomitant loss of its salvage enzyme, dihydrofolate reductase. NADPH oxidase and NOS inhibitors abrogated ECV-induced superoxide generation in the aorta of ECVexposed mice. Together, our data demonstrate that ECV exposure activates NADPH oxidase and uncouples eNOS, causing a vicious cycle of superoxide generation and vascular oxidant stress that triggers VED and hypertension with predisposition to other cardiovascular disease. [ABSTRACT FROM AUTHOR]
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Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling.
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Autor/in / Beteiligte Person: | El-Mahdy, Mohamed A. ; Ewees, Mohamed G. ; Eid, Mahmoud S. ; Mahgoup, Elsayed M. ; Khaleel, Sahar A. ; Zweier, Jay L. |
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Zeitschrift: | American Journal of Physiology: Heart & Circulatory Physiology, Jg. 322 (2022-04-01), Heft 4, S. H549- (19S.) |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 0363-6135 (print) |
DOI: | 10.1152/ajpheart.00460.2021 |
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