ArticleHypertension (Dallas, Tex. : 1979)2026
FTO/m6A Regulate Prenatal Nicotine-Induced eNOS Uncoupling and BP Susceptibility.
Article in Hypertension (Dallas, Tex. : 1979), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundPrenatal nicotine exposure from maternal smoking or e-cigarette use increases cardiovascular risk in offspring, but the underlying mechanisms remain unclear. We tested whether FTO (fat mass and obesity-associated protein)-mediated N6-methyladenosine RNA demethylation drives eNOS (endothelial nitric oxide [NO] synthase) uncoupling and programmed hypertensive susceptibility following prenatal nicotine exposure.
methodsUsing a clinically relevant rat model of chronic intermittent nicotine aerosol exposure or saline aerosol control during gestational days 4 to 21, experiments were performed in adult offspring and human umbilical vein endothelial cells.
resultsPrenatal chronic intermittent nicotine aerosol programmed a male-specific increase in hypertensive susceptibility without altering baseline blood pressure. Adult male offspring exhibited enhanced pressor responses to vasoconstrictor stimuli, impaired endothelium-dependent vasodilation, paradoxical eNOS overexpression, reduced NO bioavailability, increased superoxide and hydrogen peroxide production, impaired eNOS dimerization, and decreased tetrahydrobiopterin levels associated with reduced GTPCH1 (GTP cyclohydrolase-1) expression, consistent with eNOS uncoupling. Mechanistically, prenatal chronic intermittent nicotine aerosol increased vascular FTO expression and induced site-specific N6-methyladenosine hypomethylation of eNOS mRNA. Pharmacological inhibition of FTO with FB23-2 restored eNOS and GTPCH1 expression, improved eNOS dimerization, and normalized NO production in mesenteric arteries. In human umbilical vein endothelial cells, nicotine exposure recapitulated FTO-dependent eNOS uncoupling, which was reversed by FB23-2 or siRNA-mediated FTO knockdown.
conclusionsPrenatal nicotine exposure disrupts endothelial redox homeostasis through FTO-dependent N6-methyladenosine RNA demethylation, leading to tetrahydrobiopterin deficiency, eNOS uncoupling, and vascular dysfunction in male offspring. The FTO-tetrahydrobiopterin-eNOS pathway represents a novel epitranscriptomic mechanism underlying programmed hypertensive susceptibility and a potential therapeutic target for offspring exposed to nicotine during development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.