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

Ayako Makino1, Jorge Suarez, Hong Wang

  • 1Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California 92093-0618, USA. wdillmann@ucsd.edu.

Endocrinology
|December 17, 2008
PubMed

Insights

Thyroid hormone receptor beta (TRbeta) deficiency in heart failure leads to reduced coronary capillaries. Restoring TRbeta expression with T(3) improves blood vessel density in the heart.

Area of Science:

  • Cardiovascular Biology
  • Endocrinology
  • Molecular Medicine

Background:

  • Insufficient angiogenesis contributes to tissue ischemia and dysfunction, particularly in heart failure.
  • Decreased capillary density in the left ventricle (LV) myocardium is observed in heart failure, but underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of thyroid hormone receptors (TRs) in coronary microvascular rarefaction during pathological cardiac hypertrophy.

Main Methods:

  • Utilized a mouse model of cardiac hypertrophy induced by ascending aortic constriction (AAC).
  • Administered chronic T(3) therapy and analyzed LV microvasculature.
  • Examined TRbeta mRNA expression in coronary endothelial cells (ECs).
  • Investigated TR subtype-specific knockout mice and in vitro EC capillary network formation.
  • Assessed vascular endothelial growth factor-2 receptor (VEGFR-2) expression.

Main Results:

  • AAC induced severe microvascular rarefaction in the LV, which was reversed by T(3) administration.
  • Coronary ECs from AAC hearts showed reduced TRbeta mRNA; T(3) restored this expression.
  • TRbeta knockout mice exhibited significantly lower LV capillary density.
  • ECs from TRbeta knockout mice failed to form capillary networks in vitro.
  • T(3) administration modulated VEGFR-2, an angiogenic mediator, in AAC hearts.

Conclusions:

  • TRbeta in coronary ECs is crucial for regulating capillary density in the heart.
  • Down-regulation of TRbeta contributes to coronary microvascular rarefaction in pathological cardiac hypertrophy.
  • Targeting TRbeta may offer a therapeutic strategy for heart failure-associated ischemia.

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