Aortic effects of thyroid hormone in male mice

Research output: Contribution to journalArticle

Abstract

It is well established that thyroid hormones are required for cardiovascular functions; however, the molecular mechanisms remain incompletely understood, especially the individual contributions of genomic and non-genomic signalling pathways. In this study, we dissected how thyroid hormones modulate aortic contractility. To test the immediate effects of thyroid hormones on vasocontractility, we used a wire myograph to record the contractile response of dissected mouse aortas to the adrenergic agonist phenylephrine in the presence of different doses of T3 (3,3',5-triiodothyronine). Interestingly, we observed reduced vasoconstriction under low and high T3 concentrations, indicating an inversed U-shaped curve with maximal constrictive capacity at euthyroid conditions. We then tested for possible genomic actions of thyroid hormones on vasocontractility by treating mice for 4 days with 1 mg/L thyroxine in drinking water. The study revealed that in contrast to the non-genomic actions the aortas of these animals were hyperresponsive to the contractile stimulus, an effect not observed in endogenously hyperthyroid TRβ knockout mice. To identify targets of genomic thyroid hormone action, we analysed aortic gene expression by microarray, revealing several altered genes including the well-known thyroid hormone target gene hairless. Taken together, the findings demonstrate that thyroid hormones regulate aortic tone through genomic and non-genomic actions, although genomic actions seem to prevail in vivo. Moreover, we identified several novel thyroid hormone target genes that could provide a better understanding of the molecular changes occurring in the hyperthyroid aorta.

Details

Authors
  • Sogol Gachkar
  • Sebastian Nock
  • Cathleen Geissler
  • Rebecca Oelkrug
  • Kornelia Johann
  • Julia Resch
  • Awahan Rahman
  • Anders Arner
  • Henriette Kirchner
  • Jens Mittag
Organisations
External organisations
  • Karolinska Institutet
  • Skåne University Hospital
  • University of Lübeck
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Genetics
  • Medical Genetics

Keywords

  • aorta, gene expression, hyperthyroidism, hypothyroidism, thyroid hormone receptor β, vasoconstriction
Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalJournal of Molecular Endocrinology
Volume62
Issue number3
Publication statusPublished - 2019 Apr
Publication categoryResearch
Peer-reviewedYes