Evidence map›Paper›PMID 42040927›Full record

ArticleResearch square2026

Intermittent Hypoxia Mimicking Sleep Apnea Induces Systemic and Tissue Specific Epigenetic Changes and p16-Mediated Cellular Senescence Underlying Vascular Dysfunction.

Rene Cortese, Kylie Cataldo, Mohammad Badran, Milda Milciute, Juozas Gordevicius, Zhuanghong Qiao, Jonathan Eusey, Abdelnaby Khalyfa, David Gozal

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Rene CorteseUniversity of Kansas Medical Center.ORCID 0000-0001-9262-7828
Kylie CataldoUniversity of Missouri.
Mohammad BadranUniversity of Missouri.
Milda MilciuteVugene.
Juozas GordeviciusVugene.
Zhuanghong QiaoUniversity of Missouri.
Jonathan EuseyUniversity of Kansas Medical Center.
Abdelnaby KhalyfaMarshall University.
David GozalMarshall University.ORCID 0000-0001-8195-6036

Funding

Mentoring CoreP20GM103418 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SUSAN J. BROWN · 2012 to 2026
$63.0M
Transgenic & Gene-Targeting Shared ResourceP30CA168524 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ROY A. JENSEN · 2012 to 2026
$40.1M
Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Diane E Mahoney · 2019 to 2026
$21.5M
Coronary artery dysfunction in OSA: Role of mineralocorticoid receptorsR01HL166617 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI Mohammad Badran · 2023 to 2026
$2.5M
p16 Cellular Senescence and Vascular Dysfunction in Sleep ApneaR01HL169266 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI Rene Gabriel Cortese · 2024 to 2026
$2.2M
NCI NIH HHS P30 CA168524NHLBI NIH HHS R01 HL166617NHLBI NIH HHS R01 HL169266NIGMS NIH HHS P20 GM103418NIGMS NIH HHS P20 GM130423
6 · The paper itself

Abstract

Background: Obstructive Sleep Apnea (OSA) is a pervasive cardiovascular risk factor linked to accelerated aging and systemic inflammation. Intermittent hypoxia (IH)-a hallmark of OSA-induces cardiovascular decline, yet the underlying tissue-specific and systemic epigenetic mechanisms and the role of cellular senescence in the pathophysiology of OSA and associated cardiovascular disease (CVD) remain poorly understood. Methods: C57BL/6J male mice were exposed to IH or room air (RA) for durations ranging from 7 to 210 days. Genome-wide DNA methylation profiling was conducted on left cardiac ventricle and peripheral blood mononuclear cells (PBMCs) samples. Differentially methylated positions (DMP; q<0.05) were identified between IH and RA groups and the impact of IH duration was studied using regression models. Epigenetic age acceleration (EAA) was calculated using a multi-tissue epigenetic clock. Furthermore, p16-reporter and targeted ablation mouse models (p16-Cre Results: Chronic IH exposures significantly increased systolic and diastolic blood pressure and altered endothelial function. Epigenetic analysis identified 5,747 and 1,307 DMLs in the left cardiac ventricle and PBMCs, respectively, with minimal overlap between tissues (n=163, p=8.03 × 10 Conclusions: IH induces duration-dependent, tissue-specific epigenetic dysregulation and accelerated biological aging. Our findings provide initial evidence that p16

Indexed as

Cellular SenescenceEpigenetic Age AccelerationIntermittent HypoxiaObstructive Sleep ApneaVascular Dysfunction

Identifiers

PMID42040927
PMCPMC13105123

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Registered trials

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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.