Key result
Angiotensin 1-7 prevents T3-induced cardiomyocyte hypertrophy by increasing FOXO3 and reducing ROS.
Why the study?
High levels of T3 induce cardiac hypertrophy, and while angiotensin-(1-7) can block this hypertrophy, the underlying molecular mechanisms remain incompletely understood.
Does angiotensin-(1-7) prevent T3-induced cardiomyocyte hypertrophy through FOXO3 signaling?
Does angiotensin-(1-7) prevent T3-induced cardiomyocyte hypertrophy through FOXO3 signaling?
Angiotensin-(1-7) prevents T3-induced cardiomyocyte hypertrophy by upregulating FOXO3 and antioxidant enzymes while downregulating NF-κB.
Supports further preclinical investigation of angiotensin-(1-7); leaves open clinical translation of FOXO3 signaling in human hypertrophy.
Clinical studies have shown a correlation between thyroid disorders and cardiac diseases. High levels of triiodothyronine (T3) induce cardiac hypertrophy, a risk factor for cardiac complications and heart failure. Previous results have demonstrated that angiotensin-(1-7) is able to block T3-induced cardiac hypertrophy; however, the molecular mechanisms involved in this event have not been fully elucidated. Here, we evidenced the contribution of FOXO3 signaling to angiotensin-(1-7) effects. Angiotensin-(1-7) treatment increased nuclear FOXO3 levels and reduced p-FOXO3 levels (inactive form) in isolated cardiomyocytes. Knockdown of FOXO3 by RNA silencing abrogated the antihypertrophic effect of angiotensin-(1-7). Increased expression of antioxidant enzymes superoxide dismutase 1 (SOD1 and catalase) and lower levels of reactive oxygen species and nuclear factor-κB (NF-κB) were observed after angiotensin-(1-7) treatment in vitro. Consistent with these results, transgenic rats overexpressing angiotensin-(1-7) displayed increased nuclear FOXO3 and SOD1 levels and reduced NF-κB levels in the heart. These results provide a new molecular mechanism responsible for the antihypertrophic effect of angiotensin-(1-7), which may contribute to future therapeutic targets.
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Senger et al. (2020) studied T3-induced cardiac hypertrophy. Angiotensin-(1-7) was evaluated on FOXO3 signaling, antioxidant enzyme expression, and antihypertrophic effect. Angiotensin-(1-7) prevented T3-induced cardiomyocyte hypertrophy by increasing nuclear FOXO3 and antioxidant enzymes (SOD1/catalase) while reducing reactive oxygen species and NF-κB levels.
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