Donor-specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function

Amy Turner, Praful Aggarwal, Andrea Matter, Benjamin Olson, C. Charles Gu, Steven C. Hunt, Cora E. Lewis, Donna K. Arnett, Rachel Lorier, Ulrich Broeckel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass (LVM). Sequence analysis of the intracellular and exosomal RNA populations showed distinct expression pattern differences between hiPSC-CM lines derived from individuals with LVH and those with normal LVM. Functional analysis of hiPSC-endothelial cells (hiPSC-ECs) treated with exosomes from both hiPSC-CM groups showed significant variation in response, including differences in tube formation, migration, and proliferation. Overall, treatment of hiPSC-ECs with exosomes resulted in significant expression changes associated with angiogenesis and endothelial cell vasculogenesis. However, the hiPSC-ECs treated with exosomes from the LVH-affected donors exhibited significantly increased proliferation but decreased tube formation and migration, suggesting angiogenic dysregulation.

Original languageEnglish
Pages (from-to)H954-H968
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume320
Issue number3
DOIs
StatePublished - 2021

Keywords

  • Cardiomyocyte hypertrophy
  • Exosomes
  • Human induced pluripotent stem cells
  • Intercellular communication
  • MiRNA

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