ArticleHypertension (Dallas, Tex. : 1979)2019
Progesterone Predisposes Females to Obesity-Associated Leptin-Mediated Endothelial Dysfunction via Upregulating Endothelial MR (Mineralocorticoid Receptor) Expression.
Article in Hypertension (Dallas, Tex. : 1979), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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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.
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Who cites it
56 citing papers in PubMed, 78 citations in OpenAlex.
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- Review
- Vascular Endothelial Growth Factor Receptors 1 and 3 Mediate Placental Trophoblast Leptin Production in Preeclampsia, Inducing Vascular Dysfunction.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with KInternational journal of molecular sciences · 2026Article
- Early life stress and disruption of the ageing trajectory in female rats: Insights into the origins and mechanisms underlying the risk of hypertension.Experimental physiology · 2026Article
- A Cross-Sectional Study of Sex-Specific Associations of Renin and Electrolytes on the Development of Hypertension.Journal of clinical medicine · 2026Article
- Article
- Perivascular adipose tissue from female rats fed a high-fat diet impaired mesenteric artery vasodilation.Physiological reports · 2026Article
- AT1-AA induced hypertension during pregnancy contributes to developmental programming of hypertension in female offspring.Journal of reproductive immunology · 2025Article
- Female sex hormones do not drive the sex-specific mechanisms of obesity-related hypertension.American journal of physiology. Heart and circulatory physiology · 2025Article
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- The Clinical Implications of Progesterone in Preeclampsia.Biomolecules · 2025Review
- Salt sensitivity of blood pressure: mechanisms and sex-specific differences.Nature reviews. Cardiology · 2025Review
- Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Hormone Replacement Therapy and Cardiovascular Health in Postmenopausal Women.International journal of molecular sciences · 2025Review
- Emerging Role of Leptin in Vascular and Placental Dysfunction in Preeclampsia.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- CD4Circulation · 2025Article
- Aging and sex differences in salt sensitivity of blood pressure.Clinical science (London, England : 1979) · 2025Review
- Males and females respond differently to treatment during isolated kidney perfusion: combined effects of glucocorticoid and estradiol.Frontiers in transplantation · 2025Article
- Glucosamine-Mediated Hexosamine Biosynthesis Pathway Activation Uses ATF4 to Promote "Exercise-Like" Angiogenesis and Perfusion Recovery in PAD.Circulation · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Compelling clinical evidence indicates that obesity and its associated metabolic abnormalities supersede the protective effects of female sex-hormones and predisposes premenopausal women to cardiovascular disease. The underlying mechanisms remain poorly defined; however, recent studies have implicated overactivation of the aldosterone-MR (mineralocorticoid receptor) axis as a cause of sex-specific cardiovascular risk in obese females. Experimental evidence indicates that the MR on endothelial cells contributes to obesity-associated, leptin-induced endothelial dysfunction in female experimental models, however, the vascular-specific mechanisms via which females are predisposed to heightened endothelial MR activation remain unknown. Therefore, we hypothesized that endogenous expression of endothelial MR is higher in females than males, which predisposes them to obesity-associated, leptin-mediated endothelial dysfunction. We found that endothelial MR expression is higher in blood vessels from female mice and humans compared with those of males, and further, that PrR (progesterone receptor) activation in endothelial cells is the driving mechanism for sex-dependent increases in endothelial MR expression in females. In addition, we show that genetic deletion of either the endothelial MR or PrR in female mice prevents leptin-induced endothelial dysfunction, providing direct evidence that interaction between the PrR and MR mediates obesity-associated endothelial impairment in females. Collectively, these novel findings suggest that progesterone drives sex-differences in endothelial MR expression and predisposes female mice to leptin-induced endothelial dysfunction, which indicates that MR antagonists may be a promising sex-specific therapy to reduce the risk of cardiovascular diseases in obese premenopausal women.
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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.