MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure.
Geert C. van Almen,Wouter Verhesen,Rick van Leeuwen,Mathijs van de Vrie,Casper Eurlings,Mark W.M. Schellings,Melissa Swinnen,Jack P.M. Cleutjens,Marc A. M. J. van Zandvoort,Stephane Heymans,Blanche Schroen +10 more
Reads0
Chats0
TLDR
A role for cardiomyocyte‐derived miR‐18/19 during cardiac aging, in the fine‐tuning of cardiac ECM protein levels is supported, which could help to identify the failure‐prone heart.Abstract:
To understand the process of cardiac aging, it is of crucial importance to gain insight into the age-related changes in gene expression in the senescent failing heart. Age-related cardiac remodeling is known to be accompanied by changes in extracellular matrix (ECM) gene and protein levels. Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of ECM proteins. However, their role in age-related cardiac remodeling and heart failure is unknown. In this study, we investigated the aging-associated microRNA cluster 17–92, which targets the ECM proteins connective tissue growth factor (CTGF) and thrombospondin-1 (TSP-1). We employed aged mice with a failure-resistant (C57Bl6) and failure-prone (C57Bl6 × 129Sv) genetic background and extrapolated our findings to human age-associated heart failure. In aging-associated heart failure, we linked an aging-induced increase in the ECM proteins CTGF and TSP-1 to a decreased expression of their targeting microRNAs 18a, 19a, and 19b, all members of the miR-17–92 cluster. Failure-resistant mice showed an opposite expression pattern for both the ECM proteins and the microRNAs. We showed that these expression changes are specific for cardiomyocytes and are absent in cardiac fibroblasts. In cardiomyocytes, modulation of miR-18/19 changes the levels of ECM proteins CTGF and TSP-1 and collagens type 1 and 3. Together, our data support a role for cardiomyocyte-derived miR-18/19 during cardiac aging, in the fine-tuning of cardiac ECM protein levels. During aging, decreased miR-18/19 and increased CTGF and TSP-1 levels identify the failure-prone heart.read more
Citations
More filters
Journal ArticleDOI
MicroRNA-34a regulates cardiac ageing and function
Reinier A. Boon,Kazuma Iekushi,Stefanie Lechner,Timon Seeger,Ariane Fischer,Susanne Heydt,David Kaluza,Karine Tréguer,Guillaume Carmona,Angelika Bonauer,Anton J.G. Horrevoets,Nathalie Didier,Zenawit Girmatsion,Peter Biliczki,Joachim R. Ehrlich,Hugo A. Katus,Oliver Müller,Michael Potente,Michael Potente,Andreas M. Zeiher,Heiko Hermeking,Stefanie Dimmeler +21 more
TL;DR: Age-induced expression of miR-34a and inhibition of its target PNUTS is identified as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing DNA damage responses and telomere attrition.
Journal ArticleDOI
Matricellular Proteins in Cardiac Adaptation and Disease
TL;DR: Understanding the role of matricellular proteins in myocardial pathophysiology and identification of the functional domains responsible for their actions may lead to design of peptides with therapeutic potential for patients with heart disease.
Journal ArticleDOI
Targeting the progression of chronic kidney disease
TL;DR: The authors review drivers of fibrogenesis, including epithelial cell injury, inflammation, regeneration pathways and factors that promote the AKI-to-CKD transition, and discuss direct targeting of fibrotic pathways and therapeutic approaches that have reportedly decreased kidney fibrosis in preclinical and/or clinical studies.
Journal ArticleDOI
MicroRNAs and their roles in aging
TL;DR: How certain miRNAs can regulate aging on the level of organism lifespan, tissue aging or cellular senescence is highlighted and future approaches that might be used to investigate the mechanisms by which mi RNAs govern aging processes are discussed.
Journal ArticleDOI
Vascular Fibrosis in Aging and Hypertension: Molecular Mechanisms and Clinical Implications
TL;DR: The vascular phenotype in aging and hypertension is reviewed, focusing on arterial stiffness and vascular remodelling, and the clinical implications of these processes are highlighted and some novel molecular mechanisms of fibrosis and ECM reorganization are discussed.
References
More filters
Journal ArticleDOI
A microRNA polycistron as a potential human oncogene
Lin He,J. Michael Thomson,Michael T. Hemann,Eva Hernando-Monge,David Mu,Summer G. Goodson,Scott Powers,Carlos Cordon-Cardo,Scott W. Lowe,Gregory J. Hannon,Scott M. Hammond +10 more
TL;DR: It is found that the levels of the primary or mature microRNAs derived from the mir-17–92 locus are often substantially increased in human B-cell lymphomas, and the cluster is implicate as a potential human oncogene.
Journal ArticleDOI
How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology
Walter Paulus,Carsten Tschöpe,John E. Sanderson,Cesare Rusconi,Frank A. Flachskampf,Frank Rademakers,Paolo Marino,Otto A. Smiseth,Gilles W. De Keulenaer,Adelino F. Leite-Moreira,Attila Borbély,István Édes,Martin Louis Handoko,Stephane Heymans,Natalia Pezzali,Burkert Pieske,Kenneth Dickstein,Alan G. Fraser,Dirk L. Brutsaert +18 more
TL;DR: The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies forHFNEF.
Journal ArticleDOI
Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA
Eva van Rooij,Lillian B. Sutherland,Xiaoxia Qi,James A. Richardson,Joseph A. Hill,Eric N. Olson +5 more
TL;DR: It is found that a cardiac-specific microRNA (miR-208) encoded by an intron of the αMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of βMHC in response to stress and hypothyroidism.
Journal ArticleDOI
Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters
Andrea Ventura,Amanda G. Young,Monte M. Winslow,Laura Lintault,Alexander Meissner,Stefan J. Erkeland,Jamie J. Newman,Roderick T. Bronson,Denise Crowley,James R. Stone,Rudolf Jaenisch,Phillip A. Sharp,Tyler Jacks +12 more
TL;DR: It is shown that mice deficient for miR-17 approximately 92 die shortly after birth with lung hypoplasia and a ventricular septal defect, and a link between the oncogenic properties of miR the 1792 and its functions during B lymphopoiesis and lung development is suggested.
Journal ArticleDOI
A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure
Eva van Rooij,Lillian B. Sutherland,Ning Liu,Andrew H. Williams,John R. McAnally,Robert D. Gerard,James A. Richardson,Eric N. Olson +7 more
TL;DR: Findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to mi RNAs as potential therapeutic targets in heart disease.
Related Papers (5)
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more