Journal article
miR-486 is modulated by stretch and increases ventricular growth
JCI insight, Vol.4(19), pp.1-17
10/03/2019
DOI: 10.1172/jci.insight.125507
PMCID: PMC6795397
PMID: 31513548
Abstract
Perturbations in biomechanical stimuli during cardiac development contribute to congenital cardiac defects such as hypoplastic left heart syndrome (HLHS). This study sought to identify stretch-responsive pathways involved in cardiac development. miRNA-Seq identified miR-486 as being increased in cardiomyocytes exposed to cyclic stretch in vitro. The right ventricles (RVs) of patients with HLHS experienced increased stretch and had a trend toward higher miR-486 levels. Sheep RVs dilated from excessive pulmonary blood flow had 60% more miR-486 compared with control RVs. The left ventricles of newborn mice treated with miR-486 mimic were 16.9%-24.6% larger and displayed a 2.48-fold increase in cardiomyocyte proliferation. miR-486 treatment decreased Fox01 and Smad signaling while increasing the protein levels of Stat1. Stat1 associated with Gata-4 and serum response factor (Srf), 2 key cardiac transcription factors with protein levels that increase in response to miR-486. This is the first report to our knowledge of a stretch-responsive miRNA that increases the growth of the ventricle in vivo.
Details
- Title: Subtitle
- miR-486 is modulated by stretch and increases ventricular growth
- Creators
- Stephan Lange - University of California San DiegoIndroneal Banerjee - University of California San DiegoKatrina Carrion - University of California San DiegoRicardo Serrano - Department of Mechanical and Aerospace Engineering, UCSD, San Diego, USA.Louisa Habich - University of California San DiegoRebecca Kameny - University of California - San Francisco School of MedicineLuisa Lengenfelder - University of California San DiegoNancy Dalton - University of California San DiegoRudolph Meili - Department of Mechanical and Aerospace Engineering, UCSD, San Diego, USA.Emma Boergeson - University of GothenburgKirk Peterson - University of California San DiegoMarco Ricci - University of IowaJoy Lincoln - Nationwide Children's HospitalMajid Ghassemian - University of California San DiegoJeffery Fineman - University of California - San Francisco School of MedicineJuan C. del Alamo - Department of Mechanical and Aerospace Engineering, UCSD, San Diego, USA.Vishal Nigam - University of California San Diego
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.4(19), pp.1-17
- DOI
- 10.1172/jci.insight.125507
- PMID
- 31513548
- PMCID
- PMC6795397
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 17
- Grant note
- M15-0058 / Ake Wiberg's Foundation P30NS047101 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 20180199 / Swedish Hjart-Lungfonden S10 OD021724; S10 OD016234; NS047101; R01HL128630; HL128457 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA S150086 / Swedish Society 804418 / European Research Council; European Research Council (ERC); European Commission 2016/82 / Swedish Research Council; European Commission Knut and Alice Wallenberg Foundation; Knut & Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine R01HL128630 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) S10OD021724 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/03/2019
- Academic Unit
- Cardiothoracic Surgery
- Record Identifier
- 9984322955202771
Metrics
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