ArticleNature communications2012
Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 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.
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.
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Who cites it
180 citing papers in PubMed, 326 citations in OpenAlex.
- Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Trial
- Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b-4 stages chronic кidney disease patients: a randomized pilot study.Clinical and experimental nephrology · 2018Trial
- The association between soluble klotho and cardiovascular parameters in chronic kidney disease: results from the KNOW-CKD study.BMC nephrology · 2018Trial
- Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.PloS one · 2014Trial
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Central Osmolality Sensing for Arginine Vasopressin Release Is Mediated by WNK1-OSR1/SPAK-Kv3.1 Cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Single-Cell RNA Sequencing Delineates Renal Anti-Fibrotic Mechanisms Mediated by TRPC6 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Study on the Synergistic Effect of Klotho and KRAS on Reducing Ferroptosis After Myocardial Infarction by Regulating RAP1/ERK Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Klotho Is Cardioprotective in the mdx Mouse Model of Duchenne Muscular Dystrophy.The American journal of pathology · 2025Article
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Hypermethylation of Klotho and Peroxisome Proliferator-Activated Receptor γ Concomitant with Overexpression of DNA Methyltransferase 1 in Adenomyosis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Sex differences in the association between serum α-Klotho levels and hyperlipidemia: a cross-sectional study from NHANES 2013-2016.Scientific reports · 2025Article
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- AMP-dependent kinase stimulates the expression of αKlotho.FEBS open bio · 2024Article
- Klotho enhances diastolic function in aged hearts through Sirt1-mediated pathways.GeroScience · 2024Article
- L-shaped association of systemic immune-inflammation index (SII) with serum soluble α-Klotho in the prospective cohort study from the NHANES database.Scientific reports · 2024Article
- In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.American journal of physiology. Renal physiology · 2024Article
120 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Klotho is a membrane protein predominantly produced in the kidney that exerts some antiageing effects. Ageing is associated with an increased risk of heart failure; whether Klotho is cardioprotective is unknown. Here we show that Klotho-deficient mice have no baseline cardiac abnormalities but develop exaggerated pathological cardiac hypertrophy and remodelling in response to stress. Cardioprotection by Klotho in normal mice is mediated by downregulation of TRPC6 channels in the heart. We demonstrate that deletion of Trpc6 prevents stress-induced exaggerated cardiac remodelling in Klotho-deficient mice. Furthermore, mice with heart-specific overexpression of TRPC6 develop spontaneous cardiac hypertrophy and remodelling. Klotho overexpression ameliorates cardiac pathologies in these mice and improves their long-term survival. Soluble Klotho present in the systemic circulation inhibits TRPC6 currents in cardiomyocytes by blocking phosphoinositide-3-kinase-dependent exocytosis of TRPC6 channels. These results provide a new perspective on the pathogenesis of cardiomyopathies and open new avenues for treatment of the disease.
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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.