MiR-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors
Jayavarshni Ganesan,Deepak Ramanujam,Yassine Sassi,Andrea Ahles,Claudia Jentzsch,Stanislas Werfel,Simon Leierseder,Xavier Loyer,Mauro Giacca,Lorena Zentilin,Thomas Thum,Bernhard Laggerbauer,Stefan Engelhardt +12 more
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TLDR
In this paper, microRNAs (miRs) have been shown to regulate gene expression in the heart and dysregulation of their expression has been linked to cardiac disease, and miR-378 was found to be both necessary and sufficient to repress cardiomyocyte hypertrophy.Abstract:
Background—Several microRNAs (miRs) have been shown to regulate gene expression in the heart, and dysregulation of their expression has been linked to cardiac disease. miR-378 is strongly expressed in the mammalian heart but so far has been studied predominantly in cancer, in which it regulates cell survival and tumor growth. Methods and Results—Here, we report tight control of cardiomyocyte hypertrophy through miR-378. In isolated primary cardiomyocytes, miR-378 was found to be both necessary and sufficient to repress cardiomyocyte hypertrophy. Bioinformatic prediction suggested that factors of the mitogen-activated protein kinase (MAPK) pathway are enriched among miR-378 targets. Using mRNA and protein expression analysis along with luciferase assays, we validated 4 key components of the MAPK pathway as targets of miR-378: MAPK1 itself, insulin-like growth factor receptor 1, growth factor receptor-bound protein 2, and kinase suppressor of ras 1. RNA interference with these targets prevented the prohyper...read more
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Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy
Claudia Bang,Sandor Batkai,Seema Dangwal,Shashi Kumar Gupta,Ariana Foinquinos,Angelika Holzmann,Annette Just,Janet Remke,Karina Zimmer,Andre Zeug,Evgeni Ponimaskin,Andreas Schmiedl,Xiaoke Yin,Manuel Mayr,Rashi Halder,Andre Fischer,Stefan Engelhardt,Yuanyuan Wei,Andreas Schober,Jan Fiedler,Thomas Thum +20 more
TL;DR: It is found that cardiac fibroblasts secrete star miRNA-enriched exosomes and fibroblast-derived miR-21* is identified as a paracrine signaling mediator of cardiomyocyte hypertrophy that has potential as a therapeutic target.
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Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.
Yow Keat Tham,Yow Keat Tham,Bianca C. Bernardo,Jenny Y. Y. Ooi,Kate L. Weeks,Julie R. McMullen,Julie R. McMullen +6 more
TL;DR: New therapeutic approaches either entering clinical trials or in preclinical development, and the challenges that remain in translating these discoveries to new and approved therapies for heart failure are addressed.
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MicroRNAs in Cardiovascular Disease
TL;DR: An introduction to miRNA biology and research methodology is provided, and advances in cardiovascular research to date are highlighted, including the potential of miRNAs as therapeutic targets in cardiac and vascular disease, and their use as novel biomarkers.
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microRNAs in Cardiovascular Diseases : Current Knowledge and the Road Ahead
TL;DR: A review of the literature on miRNAs is presented and the directions toward their use in the clinic are outlined, indicating significant obstacles that need to be overcome before they enter the clinical arena.
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TL;DR: This review emphasizes current ideas and controversies within miRNA research in metabolism, and emphasizes their importance as both endocrine signalling molecules and potentially disease markers.
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TL;DR: Evidence is provided that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure as well as changes in gene expression comparable to the failing heart.
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