ArticleJournal of the American Heart Association2016
Rapamycin Attenuates Cardiac Fibrosis in Experimental Uremic Cardiomyopathy by Reducing Marinobufagenin Levels and Inhibiting Downstream Pro-Fibrotic Signaling.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Sirolimus suppresses circulating fibrocytes in idiopathic pulmonary fibrosis in a randomized controlled crossover trial.JCI insight · 2023Trial
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- The role of mechanosignaling in the control of myocardial mass.American journal of physiology. Heart and circulatory physiology · 2025Review
- Factors that influence the Na/K-ATPase signaling and function.Frontiers in pharmacology · 2025Review
- The role of autophagy in the progression of HIV infected cardiomyopathy.Frontiers in cell and developmental biology · 2024Review
- Immunosuppressive Agents-Effects on the Cardiovascular System and Selected Metabolic Aspects: A Review.Journal of clinical medicine · 2023Review
- Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats.International journal of molecular sciences · 2023Article
- The mTOR signaling pathway in cardiac aging.The journal of cardiovascular aging · 2023Article
- Cardiovascular effects of immunosuppression agents.Frontiers in cardiovascular medicine · 2022Review
- The Na/K-ATPase Signaling and SGLT2 Inhibitor-Mediated Cardiorenal Protection: A Crossed Road?The Journal of membrane biology · 2021Review
- Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis.International journal of molecular sciences · 2020Review
- Cardiac Remodeling in Chronic Kidney Disease.Toxins · 2020Review
- The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.International journal of molecular sciences · 2020Review
- Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through NaJournal of the American Heart Association · 2020Article
- Rapamycin is Effective for Upper but not for Lower Gastrointestinal Crohn's Disease-Related Stricture: A Pilot Study.Frontiers in pharmacology · 2020Article
- Comparison of anti-peritoneal fibrotic effects between an mTORC1-specific blocker and a PI3K/mTOR dual-blocker.Renal failure · 2019Article
- Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling.International journal of molecular sciences · 2019Article
- Arterial Stiffness in the Heart Disease of CKD.Journal of the American Society of Nephrology : JASN · 2019Review
- Dimethylaminomicheliolide ameliorates peritoneal fibrosis through the activation of autophagy.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Evolving concepts in the pathogenesis of uraemic cardiomyopathy.Nature reviews. Nephrology · 2019Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundExperimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K-ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K-ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway. METHODS AND
resultsBiosynthesis of MBG by cultured human JEG-3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 μmol/L of rapamycin inhibited production of MBG in human JEG-2 cells. Male Sprague-Dawley rats were subjected to either partial nephrectomy (PNx), infusion of MBG, and/or infusion of rapamycin through osmotic minipumps. PNx animals showed marked increase in plasma MBG levels (1025±60 vs 377±53 pmol/L; P<0.01), systolic blood pressure (169±1 vs 111±1 mm Hg; P<0.01), and cardiac fibrosis compared to controls. Plasma MBG levels were significantly decreased in PNx-rapamycin animals compared to PNx (373±46 vs 1025±60 pmol/L; P<0.01), and cardiac fibrosis was substantially attenuated by rapamycin treatment.
conclusionsRapamycin treatment in combination with MBG infusion significantly attenuated cardiac fibrosis. Our results suggest that rapamycin may have a dual effect on cardiac fibrosis through (1) mTOR inhibition and (2) inhibiting MBG-mediated profibrotic signaling and provide support for beneficial effect of a novel therapy for uremic cardiomyopathy.
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