Angiotensin-(1-7) prevents T3-induced cardiomyocyte hypertrophy by upregulating FOXO3/SOD1/catalase and...

Area of Science:

• Cardiovascular Research
• Endocrinology
• Molecular Biology

Background:

• Thyroid disorders are linked to cardiac diseases, with high triiodothyronine (T3) levels causing cardiac hypertrophy.
• Cardiac hypertrophy is a significant risk factor for heart failure.
• Angiotensin-(1-7) has shown potential in blocking T3-induced cardiac hypertrophy, but its molecular mechanisms are unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying the antihypertrophic effect of angiotensin-(1-7).
• To investigate the role of FOXO3 signaling in angiotensin-(1-7)-mediated protection against cardiac hypertrophy.

Main Methods:

• In vitro studies using isolated cardiomyocytes treated with angiotensin-(1-7).
• FOXO3 knockdown using RNA silencing.
• In vivo studies using transgenic rats overexpressing angiotensin-(1-7).
• Analysis of nuclear/cytoplasmic protein levels, gene expression, reactive oxygen species, and NF-κB activation.

Main Results:

• Angiotensin-(1-7) treatment increased nuclear FOXO3 levels and decreased inactive p-FOXO3 in cardiomyocytes.
• FOXO3 knockdown abolished the antihypertrophic effect of angiotensin-(1-7).
• Angiotensin-(1-7) increased antioxidant enzymes (SOD1, catalase) and reduced reactive oxygen species and NF-κB activation.
• Transgenic rats showed increased cardiac FOXO3 and SOD1, and decreased NF-κB.

Conclusions:

• FOXO3 signaling is a key molecular mechanism mediating the antihypertrophic effects of angiotensin-(1-7).
• Angiotensin-(1-7) exerts cardioprotection by enhancing antioxidant defenses and reducing inflammation via FOXO3.
• These findings highlight angiotensin-(1-7) and FOXO3 as potential therapeutic targets for cardiac hypertrophy and related complications.