Evidence map›Paper›PMID 35089811›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2022

Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling.

Mohamed A El-Mahdy, Mohamed G Ewees, Mahmoud S Eid, Elsayed M Mahgoup, Sahar A Khaleel, Jay L Zweier

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 59 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Mohamed A El-MahdyCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.
Mohamed G EweesCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.
Mahmoud S EidCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.
Elsayed M MahgoupCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.
Sahar A KhaleelCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.
Jay L ZweierCenter for Environmental and Smoking Induced Disease and the Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.ORCID 0000-0002-9414-9150
The Ohio State University · USAl-Azhar University · EG

Funding

Role of Cytoglobin in the Regulation of Vascular ToneR01HL131941 · NHLBI · OHIO STATE UNIVERSITY · PI JAY Louis ZWEIER · 2017 to 2026
$5.7M
Mechanisms of Nicotine Inhalation-Induced Cardiovascular DiseaseR01HL135648 · NHLBI · OHIO STATE UNIVERSITY · PI ZWEIER, JAY LOUIS · 2017 to 2021
$2.6M
HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL131941HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL135648NHLBI NIH HHS R01 HL131941NHLBI NIH HHS R01 HL135648
6 · The paper itself

Abstract

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 air-exposed 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 ECV-exposed 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.

Indexed as

Cardiovascular DiseasesElectronic Nicotine Delivery SystemsHypertensionAnimalsEndothelium, VascularFemaleMaleMiceNADPH OxidasesNicotineNitric OxideNitric Oxide Synthase Type IIIPeroxynitrous AcidSuperoxidesNADPH OxidasesNicotineNitric OxideNitric Oxide Synthase Type IIIPeroxynitrous AcidSuperoxidese-cigaretteseNOS uncouplingNADPH oxidasetetrahydrobiopterinvascular endothelial dysfunction

Identifiers

PMID35089811
PMCPMC8917923
OpenAlexW4210696949

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.