ArticleEndocrinology2019
Sexual Dimorphism in Obesity-Associated Endothelial ENaC Activity and Stiffening in Mice.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.
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
21 citing papers in PubMed, 34 citations in OpenAlex.
- ENAC blockade reduces blood pressure and arterial stiffness in adults with obesity and insulin resistance.American journal of physiology. Heart and circulatory physiology · 2026Trial
- Impaired nitric oxide-dependent endothelial function in young male individuals with obesity before the onset of symptoms and complications.Experimental physiology · 2026Article
- Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Bone marrow monocytes and macrophages from mice lacking βENaC and ASIC2 have a reduced chemotactic migration response and polarization.Physiological reports · 2024Article
- Endothelial cell serum and glucocorticoid regulated kinase 1 (SGK1) mediates vascular stiffening.Metabolism: clinical and experimental · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Sex-specific effects of a high fat diet on aortic inflammation and dysfunction.Scientific reports · 2023Article
- Vascular endothelial mineralocorticoid receptors and epithelial sodium channels in metabolic syndrome and related cardiovascular disease.Journal of molecular endocrinology · 2023Review
- Suppressed vascular Rho-kinase activation is a protective cardiovascular mechanism in obese female mice.Bioscience reports · 2023Article
- Endothelial cell-specific mineralocorticoid receptor activation promotes diastolic dysfunction in diet-induced obese male mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Role of epithelial sodium channel-related inflammation in human diseases.Frontiers in immunology · 2023Review
- ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.American journal of physiology. Heart and circulatory physiology · 2022Article
- Sex Differences in Adiposity and Cardiovascular Diseases.International journal of molecular sciences · 2022Review
- SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice.GeroScience · 2022Article
- Endothelial sodium channel activation mediates DOCA-salt-induced endothelial cell and arterial stiffening.Metabolism: clinical and experimental · 2022Article
- Cystamine reduces vascular stiffness in Western diet-fed female mice.American journal of physiology. Heart and circulatory physiology · 2022Article
- Mutation of the 5'-untranslated region stem-loop mRNA structure reduces type I collagen deposition and arterial stiffness in male obese mice.American journal of physiology. Heart and circulatory physiology · 2021Article
- Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.Frontiers in physiology · 2021Article
- TRAF3IP2 (TRAF3 Interacting Protein 2) Mediates Obesity-Associated Vascular Insulin Resistance and Dysfunction in Male Mice.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Obesity and cardiovascular disease in women.International journal of obesity (2005) · 2020Review
Corrections and comments
- Retraction · 2020-02-14Duplication of/in Article ·
- Erratum issued
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity and insulin resistance stiffen the vasculature, with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of women with obesity and insulin resistance to arterial stiffening may explain their heightened risk for CVD. However, the cellular mechanisms by which females are more vulnerable to arterial stiffening associated with obesity and insulin resistance remain largely unknown. In this study, we provide evidence that female mice are more susceptible to Western diet-induced endothelial cell stiffening compared with age-matched males. Mechanistically, we show that the increased stiffening of the vascular intima in Western diet-fed female mice is accompanied by enhanced epithelial sodium channel (ENaC) activity in endothelial cells (EnNaC). Our data further indicate that: (i) estrogen signaling through estrogen receptor α (ERα) increases EnNaC activity to a larger extent in females compared with males, (ii) estrogen-induced activation of EnNaC is mediated by the serum/glucocorticoid inducible kinase 1 (SGK-1), and (iii) estrogen signaling stiffens endothelial cells when nitric oxide is lacking and this stiffening effect can be reduced with amiloride, an ENaC inhibitor. In aggregate, we demonstrate a sexual dimorphism in obesity-associated endothelial stiffening, whereby females are more vulnerable than males. In females, endothelial stiffening with obesity may be attributed to estrogen signaling through the ERα-SGK-1-EnNaC axis, thus establishing a putative therapeutic target for female obesity-related vascular stiffening.
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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.