miR-486 is modulated by stretch and increases ventricular growth. JCI Insight 2019 Sep 12;4(19)
Date
09/13/2019Pubmed ID
31513548Pubmed Central ID
PMC6795397DOI
10.1172/jci.insight.125507Scopus ID
2-s2.0-85072970284 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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 FoxO1 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.
Author List
Lange S, Banerjee I, Carrion K, Serrano R, Habich L, Kameny R, Lengenfelder L, Dalton N, Meili R, Börgeson E, Peterson K, Ricci M, Lincoln J, Ghassemian M, Fineman J, Del Álamo JC, Nigam VAuthor
Joy Lincoln PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Biomechanical Phenomena
Cell Proliferation
Cells, Cultured
Heart Ventricles
Humans
Hypoplastic Left Heart Syndrome
Mechanotransduction, Cellular
Mice
MicroRNAs
Myocytes, Cardiac
STAT1 Transcription Factor
Sheep