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Thyroid hormone receptor blockade by amiodarone disrupts angiogenesis via VEGFα, WNT7A, BMP, and PI3K/AKT pathways in

Juhi Vaishnav1, Suresh Balakrishnan1,2

  • 1Dr. Vikram Sarabhai Institute of Cell and Molecular Biology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|September 13, 2025
PubMed
Abstract

Insights

Thyroid hormone signaling is essential for embryonic blood vessel formation. Blocking thyroid hormone receptors with amiodarone impairs angiogenesis by down-regulating key growth factors and signaling pathways, leading to developmental defects.

Area of Science:

  • Developmental Biology
  • Endocrinology
  • Vascular Biology

Background:

  • Thyroid hormones (TH) are crucial for embryonic vascular development.
  • The exact molecular mechanisms of TH in angiogenesis are not fully understood.

Purpose of the Study:

  • To investigate how amiodarone, a thyroid hormone receptor (TR) blocker, affects angiogenesis and molecular signaling in chick embryos.
  • To elucidate the role of thyroid hormone signaling in embryonic vascular formation.

Main Methods:

  • Pharmacological blockade of TR using amiodarone in chick embryos.
  • Morphological analysis and chorioallantoic membrane assays to assess vascular development.
  • Molecular profiling (transcript and protein levels) of angiogenic regulators.
  • In silico docking, deiodinase activity assays, and western blotting to confirm TR binding and thyroid hormone status.

Main Results:

  • Amiodarone induced morphological defects and impaired angiogenesis, evidenced by reduced vessel density and branching.
  • Key angiogenic factors like VEGFα, WNT7A, BMP2/6, and PI3K/AKT pathways were significantly downregulated.
  • Amiodarone treatment led to reduced T3 levels, confirming hypothyroidism and disrupted TH signaling.

Conclusions:

  • Thyroid hormone signaling is vital for embryonic angiogenesis.
  • Disruption of TR activation by amiodarone impairs vascular development via suppression of VEGFα, WNT7A, BMPs, and PI3K/AKT pathways.
  • Findings offer insights into TH-related developmental disorders and potential therapeutic targets for vascular dysfunction.
Keywords:
apoptosischorioallantoic membraneephrinsprogrammed cell deathvasculogenesis

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