ArticleRedox biology2021
Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Fibulin 2 Deficiency Drives Epigenetic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Steroid hormones and nephrolithiasis: regulation of urine components metabolism and inflammation.Biology of sex differences · 2026Review
- Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management.Nutrients · 2025Review
- Sex differences in the association between Life's Essential 8 and serum anti-aging Klotho protein levels: a cross-sectional analysis in middle-aged to older adults.Frontiers in aging · 2025Article
- The role of age and sex in non-linear dilution adjustment of spot urine arsenic.BMC nephrology · 2024Article
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Dietary caffeine and its negative link to serum Klotho concentrations: evidence from the National Health and Nutrition Examination Survey.Frontiers in nutrition · 2024Article
- Association between serum Klotho concentration and hypertension in postmenopausal women, a cross-sectional study from NHANES 2013-2016.BMC geriatrics · 2023Article
- Inhibition of miR-101-3p prevents human aortic valve interstitial cell calcification through regulation of CDH11/SOX9 expression.Molecular medicine (Cambridge, Mass.) · 2023Article
- Association of serum Klotho levels with cancer and cancer mortality: Evidence from National Health and Nutrition Examination Survey.Cancer medicine · 2023Article
- Transplantation of bone marrow cells from miR150 knockout mice improves senescence-associated humoral immune dysfunction and arterial stiffness.Metabolism: clinical and experimental · 2022Article
- Aging impairs arterial compliance via Klotho-mediated downregulation of B-cell population and IgG levels.Cellular and molecular life sciences : CMLS · 2022Article
- In Vivo Cardiac-specific Expression of Adenylyl Cyclase 4 Gene Protects against Klotho Deficiency-induced Heart Failure.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Stem cell therapy for pulmonary arterial hypertension: An update.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Review
- Adult Mouse Kidney Stem Cells Orchestrate the De Novo Assembly of a Nephron via Sirt2-Modulated Canonical Wnt/β-Catenin Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Renal Function Mediates the Association Between Klotho and Congestive Heart Failure Among Middle-Aged and Older Individuals.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objective and hypothesisKlotho is an aging-suppressor gene. Mutation of Klotho gene causes hyperphosphatemia and acute heart failure. However, the relationship of hyperphosphatemia and acute heart failure is unclear. We hypothesize that hyperphosphatemia mediates Klotho deficiency-induced acute heart failure and further that therapeutic reduction of hyperphosphatemia prevents acute heart failure in Klotho mutant (KL(-/-)) mice. METHODS AND
resultsA significant elevation of serum phosphorus levels and a large reduction of heart function were found in KL(-/-) mice by six weeks of age. Normalization of serum phosphorus levels by low phosphate diet (LPD) rescued Klotho deficiency-induced heart failure and extended lifespan in male mice. Klotho deficiency impaired cardiac mitochondrial respiratory enzyme function and increased superoxide production, oxidative stress, and cardiac cell apoptosis in male KL(-/-) mice which can be eliminated by LPD. LPD, however, did not rescue hyperphosphatemia or heart failure in female KL(-/-) mice. LPD did not affect estrogen depletion in female KL(-/-) mice. Normalization of serum estrogen levels by treatment with 17β-estradiol prevented hyperphosphatemia and heart failure in female KL(-/-) mice. Mechanistically, treatment with 17β-estradiol rescued hyperphosphatemia via inhibiting renal Na-Pi co-transporter expression. Normalization of serum phosphorus levels by treatment with 17β-estradiol also abolished cardiac mitochondrial respiratory enzyme dysfunction, ROS overproduction, oxidative stress and cardiac cell apoptosis in female KL(-/-) mice.
conclusionKlotho deficiency causes acute heart failure via hyperphosphatemia in male mice which can be prevented by LPD. 17β-estradiol prevents Klotho deficiency-induced hyperphosphatemia and heart failure by eliminating upregulation of renal Na-Pi co-transporter expression in female mice.
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