Key result
ALK7 disruption aggravated cardiac hypertrophy and fibrosis in response to pressure overload, whereas ALK7 overexpression protected against it via inhibition of the MEK-ERK1/2 signaling pathway.
Why the study?
Does ALK7 overexpression or disruption affect pathological cardiac hypertrophy in mouse models of pressure overload?
Does ALK7 overexpression or disruption affect pathological cardiac hypertrophy in mouse models of pressure overload?
ALK7 acts as a novel negative regulator of pathological cardiac hypertrophy via inhibition of the MEK-ERK1/2 signaling pathway, highlighting its potential as a therapeutic target.
ALK7 modulation affects experimental hypertrophy; leaves open clinical relevance and therapeutic targeting in patients.
AIMS: Activin receptor-like kinase 7 (ALK7), one of the type I transforming growth factor-β receptors, is expressed in various tissues, including the heart. However, the participation of ALK7 in the regulation of cardiac hypertrophy has not yet been studied. Here, we sought to determine the regulatory role and underlying mechanisms of ALK7 in cardiac hypertrophy. METHODS AND RESULTS: We performed aortic banding (AB) in ALK7-knockout mice, cardiac-specific ALK7-transgenic mice, and the wild-type littermates of these mice. Cardiac hypertrophy was evaluated using pathological analysis, echocardiographic measurement, haemodynamic measurement, and molecular analysis. Our results revealed that ALK7 disruption led to an aggravated cardiac hypertrophic response that was accompanied by increased cardiac fibrosis and reduced contractile function, whereas cardiac-specific ALK7 overexpression exhibited the opposite phenotype in response to pressure overload. Similarly, ALK7 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, we demonstrated that ALK7-dependent cardioprotection was mediated largely through inhibition of the MEK-ERK1/2 signalling pathway. CONCLUSION: Our data suggest that ALK7 acts as a novel regulator of pathological cardiac hypertrophy via the negative regulation of MEK-ERK1/2 signalling and may serve as a potential therapeutic target for pathological cardiac hypertrophy.
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Huang et al. (2015) studied Pathological cardiac hypertrophy. ALK7 disruption or overexpression vs. Wild-type littermates was evaluated on Cardiac hypertrophic response, cardiac fibrosis, and contractile function. ALK7 disruption aggravated cardiac hypertrophy and fibrosis in response to pressure overload, whereas ALK7 overexpression protected against it via inhibition of the MEK-ERK1/2 signaling pathway.
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