ArticleCirculation. Heart failure2013
A novel immunomodulator, FTY-720 reverses existing cardiac hypertrophy and fibrosis from pressure overload by targeting NFAT (nuclear factor of activated T-cells) signaling and periostin.
Article in Circulation. Heart failure, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- Pak1 overexpression is associated with mild concentric cardiac remodeling and favorable systolic and diastolic functional indices in transgenic mice.Frontiers in cardiovascular medicine · 2026Article
- Cardiomyocyte Rac1 signaling in hypertrophy, arrhythmia, and cardiac stress adaptation.Journal of molecular and cellular cardiology plus · 2025Review
- Angiotensin II Promotes Progressive Activation of Fibrogenic Periostin-Lineage Cells in Lung and Kidney.Cells · 2025Article
- p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.Comprehensive Physiology · 2025Review
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- Qishen Yiqi alleviates periostin-mediated cardiac fibrosis and hypertrophy in Dahl hypertensive rat hearts and angiotensin II-induced cardiac organoids.Frontiers in pharmacology · 2025Article
- Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.Theranostics · 2025Article
- Expression of the Pro-Fibrotic Marker Periostin in a Mouse Model of Duchenne Muscular Dystrophy.Biomedicines · 2024Article
- Sphingosine-1-phosphate levels are inversely associated with left ventricular and atrial chamber volume and cardiac mass in men : The Study of Health in Pomerania (SHIP).Clinical research in cardiology : official journal of the German Cardiac Society · 2023Article
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Serum Periostin May Help to Identify Patients with Poor Collaterals in the Hyperacute Phase of Ischemic Stroke.Diagnostics (Basel, Switzerland) · 2022Article
- Resveratrol against Cardiac Fibrosis: Research Progress in Experimental Animal Models.Molecules (Basel, Switzerland) · 2021Review
- Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts.International journal of cardiology. Heart & vasculature · 2021Article
- Deletion of P21-activated kinase-1 induces age-dependent increased visceral adiposity and cardiac dysfunction in female mice.Molecular and cellular biochemistry · 2021Article
- Silencing miR-370-3p rescues funny current and sinus node function in heart failure.Scientific reports · 2020Article
- Challenges and Opportunities for Therapeutic Targeting of Calmodulin Kinase II in Heart.Frontiers in pharmacology · 2020Review
- Sphingolipid Mediators of Myocardial Pathology.Journal of lipid and atherosclerosis · 2020Review
- Sphingolipids in the Heart: From Cradle to Grave.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHypertension or aortic stenosis causes pressure overload, which evokes hypertrophic myocardial growth. Sustained cardiac hypertrophy eventually progresses to heart failure. Growing evidence indicates that restraining hypertrophy could be beneficial; here, we discovered that FTY-720, an immunomodulator for treating multiple sclerosis, can reverse existing cardiac hypertrophy/fibrosis. METHODS AND
resultsMale C57/Bl6 mice underwent transverse aortic constriction (TAC) for 1 week followed by FTY-720 treatment for 2 weeks under continuing TAC. Compared with vehicle-treated TAC hearts, FTY-720 significantly reduced ventricular mass, ameliorated fibrosis, and improved cardiac performance. Mechanistic studies led us to discover that FTY-720 appreciably inhibited nuclear factor of activated T-cells (NFAT) activity. Moreover, we found that in primary cardiomyocytes (rat and human) pertussis toxin (Gi-coupled receptor inhibitor) substantially blocked the antihypertrophic effect of FTY-720. This observation was confirmed in a mouse model of pressure overload. Interestingly, gene array analysis of TAC hearts revealed that FTY-720 profoundly decreased gene expression of a group of matricellular proteins, of which periostin was prominent. Analysis of periostin protein expression in TAC-myocardium, as well as in rat and human cardiac fibroblasts, confirmed the array data. Moreover, we found that FTY-720 treatment or knockdown of periostin protein was able to inhibit transforming growth factor-β responsiveness and decrease collagen expression.
conclusionsFTY-720 alleviates existing cardiac hypertrophy/fibrosis through mechanisms involving negative regulation of NFAT activity in cardiomyocytes and reduction of periostin expression allowing for a more homeostatic extracellular compartment milieu. Together, FTY-720 or its analogues could be a promising new approach for treating hypertrophic/fibrotic heart disease.
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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.