Research Focus >Hypoplastic Left Heart Syndrome Project

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Hypoplastic Left Heart Syndrome (HLHS) is an embryonic/infantile cardiac defect that affects the normal blood flow in the heart. Specifically, the left ventricle is severely underdeveloped in HLHS patients, with the right ventricle taking over some of the necessary work to supply the body with blood. Several lines of evidence indicate that altered biomechanical stimuli of cardiomyocytes may contribute to HLHS.
We investigated stretch responsive biomechanical signaling pathways that may play a role in this devastating syndrome.

HLHS Morphological differences between normal and HLHS hearts. Figure adapted from our recent article published in JCI Insight.

Functions of miR-486

We sought to identify stretch responsive micro-RNA's (miRNAs) that could be used to enhance cardiac contractility in HLHS patients. We identified miR-486 as increased in right ventricles of HLHS patients, a sheep model of increased right ventricular work, and cultured cardiomyocytes exposed to cyclic stretch.
miR-486 function is elicited through increased cardiac proliferation of embryonic cardiomyocytes, increased cardiomyocyte growth, and altered cardiac signaling through FoxO1, Smad, Srf, Gata-4 and Stat1.

miR-486 alters cardiac signaling

Related manuscripts

  • miR-486 is modulated by stretch and increases ventricular growth. JCI Insight. 2019 Sep 12. doi:10.1172/jci.insight.125507

  • Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-beta signaling. J Mol Cell Cardiol. 2014 Nov 13;79C:133-144. doi: 10.1016/j.yjmcc.2014.11.003. PMID: 25446186

Collaborators on this project

  • Dr. Vishal Nigam, Department of Pediatrics (Cardiology), Seattle Children’s Research Institute and University of Washington, Seattle, USA
  • Dr. Juan C. del Álamo, 4 Department of Mechanical and Aerospace Engineering, University of California San Diego, San Diego, USA