ArticleEuropean journal of heart failure2015
Up-regulation of micro-RNA765 in human failing hearts is associated with post-transcriptional regulation of protein phosphatase inhibitor-1 and depressed contractility.
Article in European journal of heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Long noncoding RNAOpen medicine (Warsaw, Poland) · 2023Article
- The roles and mechanisms of epigenetic regulation in pathological myocardial remodeling.Frontiers in cardiovascular medicine · 2022Review
- Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.Pflugers Archiv : European journal of physiology · 2021Review
- miR-137 suppresses cell growth and extracellular matrixdegradation through regulating ADAMTS-5 in chondrocytes.American journal of translational research · 2019Article
- Age-Dependent Protein Expression of Serine/Threonine Phosphatases and Their Inhibitors in the Human Cardiac Atrium.Advances in medicine · 2019Article
- A novel human S10F-Hsp20 mutation induces lethal peripartum cardiomyopathy.Journal of cellular and molecular medicine · 2018Article
- Identification of the Functional Autophagy-Regulatory Domain in HCLS1-Associated Protein X-1 That Resists Against Oxidative Stress.DNA and cell biology · 2018Article
- HAX-1 regulates SERCA2a oxidation and degradation.Journal of molecular and cellular cardiology · 2018Article
- Article
- Prediction of miRNA-disease Associations using an Evolutionary Tuned Latent Semantic Analysis.Scientific reports · 2017Article
- Negative Adrenergic Feedback Specific to Phospholamban.JACC. Basic to translational science · 2017Article
- Pericardial Fluid Exosomes: A New Material to Treat Cardiovascular Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Article
- MicroRNA-765 regulates neural stem cell proliferation and differentiation by modulating Hes1 expression.American journal of translational research · 2016Article
- Should we treat heart failure with phosphatase inhibitors? Better to start at the end.Journal of molecular and cellular cardiology · 2015Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
aimsImpaired sarcoplasmic reticulum (SR) Ca(2+) cycling and depressed contractility, a hallmark of human and experimental heart failure, has been partially attributed to increased protein phosphatase 1 (PP-1) activity, associated with down-regulation of its endogenous inhibitor-1. The levels and activity of inhibitor-1 are reduced in failing hearts, contributing to dephosphorylation and inactivation of key calcium cycling proteins. Therefore, we investigated the mechanisms that mediate decreases in inhibitor-1 by post-transcriptional modification. METHODS AND
resultsBioinformatics revealed that 17 human microRNAs may serve as modulators of inhibitor-1. However, real-time PCR analysis identified only one of these microRNAs, miR-765, as being increased in human failing hearts concomitant with decreased inhibitor-1 levels. Expression of miR-765 in HEK293 cells or mouse ventricular myocytes confirmed suppression of inhibitor-1 levels through binding of this miR-765 to the 3'-untranslated region of inhibitor-1 mRNA. To determine the functional significance of miR-765 in Ca(2+) cycling, pri-miR-765 as well as a non-translated nucleotide sequence (miR-Ctrl) were expressed in adult mouse ventricular myocytes. The inhibitor-1 expression levels were decreased, accompanied by enhanced PP-1 activity in the miR-765 cardiomyocytes, and these reflected depressed contractile mechanics and Ca(2+) transients, compared with the miR-Ctrl group. The depressive effects were associated with decreases in the phosphorylation of phospholamban and SR Ca(2+) load. These miR-765 negative inotropic effects were abrogated in inhibitor-1-deficient cardiomyocytes, suggesting its apparent specificity for inhibitor-1.
conclusionsmiR-765 levels are increased in human failing hearts. Such increases may contribute to depressed cardiac function through reduced inhibitor-1 expression and enhanced PP-1 activity, associated with reduced SR Ca(2+) load.
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