RhoA/ROCK may involve in cardiac hypertrophy induced by experimental hyperthyroidism

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Molecular Biology

Background:

• Hyperthyroidism is associated with cardiovascular complications, including cardiac dysfunction.
• The RhoA/Rho-kinase (ROCK) signaling pathway plays a critical role in cardiovascular regulation.
• The specific involvement of the RhoA/ROCK pathway in hyperthyroid cardiac dysfunction remains to be fully elucidated.

Purpose of the Study:

• To investigate the role of the RhoA/ROCK signaling pathway in hyperthyroidism-induced cardiovascular dysfunction.
• To evaluate the therapeutic potential of fasudil, a ROCK inhibitor, in ameliorating these cardiac abnormalities.

Main Methods:

• Male Sprague-Dawley rats were administered l-thyroxine (T(4)) to induce hyperthyroidism.
• Rats received fasudil (low or high dose) concurrently with T(4) or T(4) alone.
• Cardiac hypertrophy, apoptosis, and RhoA/ROCK pathway activity markers were assessed using morphometric, hemodynamic, Western blotting, and RT-PCR analyses.

Main Results:

• T(4) treatment led to increased heart weight to body weight ratio and cardiac hypertrophy, which were significantly reduced by fasudil.
• Fasudil dose-dependently inhibited T(4)-induced increases in Rho-kinase activity and activator protein 1, and decreased c-FLIP(L) expression.
• Fasudil treatment attenuated T(4)-induced apoptosis, as evidenced by reduced TUNEL-positive cells and altered Bax/Bcl-2 expression.

Conclusions:

• The RhoA/ROCK signaling pathway is implicated in the cardiac hypertrophy and apoptosis associated with experimental hyperthyroidism.
• Inhibition of the RhoA/ROCK pathway using fasudil demonstrates a potential therapeutic strategy for managing hyperthyroid heart disease.