ArticleEuropean heart journal2013
Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.
Article in European heart journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Obesity and episodic memory function.The journal of physiological sciences : JPS · 2018Pooled it
- Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications.Current hypertension reports · 2015Pooled it
- Effects of mineralocorticoid receptor antagonists on sex hormones and body composition in patients with primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Trial
- Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.Experimental gerontology · 2016Trial
- Effect of mineralocorticoid receptor blockade on hippocampal-dependent memory in adults with obesity.Obesity (Silver Spring, Md.) · 2015Trial
- Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes.Diabetes · 2015Trial
- Biphasic regulation of myogenesis by ALDH2, aldosterone, and oxidative stress.Pflugers Archiv : European journal of physiology · 2026Article
- Regulating effect of genistein on the association of endothelial activation and stress index with atherosclerotic cardiovascular disease risk: a cross-sectional study of the NHANES database.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Pharmacological inhibition of IRAK1/4 ameliorates high-fat diet-induced vascular dysfunction and cognitive impairment.Molecular biology reports · 2026Article
- Cardiovascular risk in primary aldosteronism: inflammatory drivers, residual risk, and emerging combination strategies.Frontiers in endocrinology · 2026Review
- Single-Cell Analysis Reveals a Critical Role for Macrophage Epsins in Regulating the Origin of Foam Cells in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Article
- Current Application of Mineralocorticoid Antagonist (MRA) in Heart Failure and CKD: Does Non-Steroidal Drug Add Novel Insights.Biomedicines · 2025Review
- Effect of esaxerenone on the onset of aortic endothelial dysfunction and circulating microparticles in type 1 diabetic male mice.Scientific reports · 2024Article
- Extra-adrenal aldosterone: a mini review focusing on the physiology and pathophysiology of intrarenal aldosterone.Endocrine · 2024Review
- Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.Cardiovascular diabetology · 2023Article
- Neutral Effect of Skeletal Muscle Mineralocorticoid Receptor on Glucose Metabolism in Mice.International journal of molecular sciences · 2023Article
- A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice.Journal of atherosclerosis and thrombosis · 2023Article
- Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice.Basic research in cardiology · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. METHODS AND
resultsC57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR.
conclusionObesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.
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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.