Thyroid hormone receptor-β is associated with coronary angiogenesis during pathological cardiac hypertrophy

Ayako Makino, Jorge Suarez, Hong Wang, Darrell D. Belke, Brian T. Scott, Wolfgang H. Dillmann

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Insufficient angiogenesis is one of the causes leading to tissue ischemia and dysfunction. In heart failure, there is increasing evidence showing decreased capillary density in the left ventricle (LV) myocardium, although the detailed mechanisms contributing to it are not clear. The goal of this study was to investigate the role of thyroid hormone receptors (TRs) in the coronary microvascular rarefaction under pathological cardiac hypertrophy. The LV from hypertrophied/failing hearts induced by ascending aortic constriction (AAC) exhibited severe microvascular rarefaction, and this phenomenon was restored by chronic T 3 administration. Coronary endothelial cells (ECs) isolated from AAC hearts expressed lower TRβ mRNA than control ECs, and chronic T 3 administration restored TRβ mRNA expression level in AAC hearts to the control level. Among different TR subtype-specific knockout mice, TRβ knockout and TRα/TRβ double-knockout mice both exhibited significantly less capillary density in LV compared with wild-type mice. In vitro, coronary ECs isolated from TRβ knockout mice lacked the ability to form capillary networks. In addition, we identified that kinase insert domain protein receptor/fetal liver kinase-1 (vascular endothelial growth factor-2 receptor) was one of the angiogenic mediators controlled by T 3 administration in the AAC heart. These data suggest that TRβ in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRβ results in coronary microvascular rarefaction during pathological hypertrophy.

Original languageEnglish (US)
Pages (from-to)2008-2015
Number of pages8
JournalEndocrinology
Volume150
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Endocrinology

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