Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration

J Mol Cell Cardiol. 2024 Jun:191:7-11. doi: 10.1016/j.yjmcc.2024.04.007. Epub 2024 Apr 10.

Abstract

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Keywords: Cardiomyocyte proliferation; Heart regeneration; Immune response; Macrophage; Triiodothyronine (T3).

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Proliferation* / drug effects
  • Heart / drug effects
  • Heart / physiopathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocytes* / drug effects
  • Monocytes* / metabolism
  • Myocytes, Cardiac* / drug effects
  • Myocytes, Cardiac* / metabolism
  • Regeneration* / drug effects
  • Triiodothyronine* / pharmacology

Substances

  • Triiodothyronine