ArticleArteriosclerosis, thrombosis, and vascular biology2011
Aldosterone regulates vascular gene transcription via oxidative stress-dependent and -independent pathways.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 90 citations in OpenAlex.
- Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues.The Journal of endocrinology · 2026Review
- Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Blocking mineralocorticoid signaling with esaxerenone reduces atherosclerosis in hyperglycemic ApoE KO mice without affecting blood pressure and glycolipid metabolism.Scientific reports · 2025Article
- Primary Aldosteronism Influences Cardiac Structure, Function, and Disease Risk: Evidence From Mendelian Randomization Analysis.Journal of clinical hypertension (Greenwich, Conn.) · 2024Article
- Effect of esaxerenone on the onset of aortic endothelial dysfunction and circulating microparticles in type 1 diabetic male mice.Scientific reports · 2024Article
- Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond.Hypertension (Dallas, Tex. : 1979) · 2024Review
- The Mineralocorticoid Receptor in the Vasculature: Friend or Foe?Annual review of physiology · 2024Review
- Smooth Muscle Mineralocorticoid Receptor Promotes Hypertension After Preeclampsia.Circulation research · 2023Article
- Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.International journal of molecular sciences · 2023Review
- Smooth muscle mineralocorticoid receptor as an epigenetic regulator of vascular ageing.Cardiovascular research · 2023Article
- Mechanism by Which Inflammation and Oxidative Stress Induce Mineralocorticoid Receptor Gene Expression in Aging Vascular Smooth Muscle Cells.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Mineralocorticoid receptor activation and antagonism in cardiovascular disease: cellular and molecular mechanisms.Kidney international supplements · 2022Review
- Dexamethasone-associated metabolic effects in male mice are partially caused by depletion of endogenous corticosterone.Frontiers in endocrinology · 2022Article
- Sex differences in the time course and mechanisms of vascular and cardiac aging in mice: role of the smooth muscle cell mineralocorticoid receptor.American journal of physiology. Heart and circulatory physiology · 2021Article
- Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.Canadian journal of physiology and pharmacology · 2020Article
- Obesity and cardiovascular disease in women.International journal of obesity (2005) · 2020Review
- The endothelial mineralocorticoid receptor: Contributions to sex differences in cardiovascular disease.Pharmacology & therapeutics · 2019Review
- PKCδ Mediates Mineralocorticoid Receptor Activation by Angiotensin II to Modulate Smooth Muscle Cell Function.Endocrinology · 2019Article
- Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction.EBioMedicine · 2019Review
- Role of Aldosterone and Mineralocorticoid Receptor in Cardiovascular Aging.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAldosterone (Aldo) antagonism prevents cardiovascular mortality by unclear mechanisms. Aldo binds to the mineralocorticoid receptor (MR), a ligand-activated transcription factor, which is expressed in human vascular cells. Here we define the early Aldo-regulated vascular transcriptome and investigate the mechanisms of gene regulation by Aldo in the vasculature that may contribute to vascular disease. METHODS AND
resultsGene expression profiling of Aldo-treated mouse aortas identified 72 genes regulated by Aldo. These genes are overrepresented in Gene Ontology categories involved in vascular function and disease. Quantitative reverse transcription-polymerase chain reaction was used to confirm and further explore mechanisms of vascular gene regulation by Aldo. Aldo-regulated vascular gene expression was inhibited by actinomycin D and MR antagonists supporting a transcriptional MR-dependent mechanism. Aldo regulation of a subset of genes was enhanced in the setting of vascular endothelial denudation and blocked by the free radical scavenger Tempol, supporting synergy between Aldo and vascular injury that is oxidative stress dependent. In the aortic arch, a region predisposed to atherosclerosis, the injury-enhanced genes also demonstrated enhanced expression compared with the descending aorta, both at baseline and after Aldo exposure. Furthermore, the clinically beneficial MR antagonist spironolactone inhibited expression of the identified genes in aortic tissue from humans with atherosclerosis.
conclusionsThis study defines the Aldo-regulated vascular transcriptome and characterizes a subset of proatherogenic genes with enhanced Aldo-stimulated, oxidative stress-dependent expression in the setting of vascular injury and in areas predisposed to atherosclerosis. Inhibition of MR regulation of these genes may play a role in the protective effects of Aldo antagonists in patients with vascular disease, and these pathways may provide novel drug targets to prevent atherosclerosis in humans.
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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.