Key result
LNA-antimiR-154 protects against cardiac dysfunction in mice, yielding ~33% higher fractional shortening versus control.
Why the study?
The role of miR-154 in sustained pressure overload-induced cardiac hypertrophy and fibrosis had not been assessed.
Does therapeutic inhibition of miR-154 improve cardiac function and attenuate adverse cardiac remodelling in a mouse model of pressure overload-induced cardiac hypertrophy?
Does therapeutic inhibition of miR-154 improve cardiac function and attenuate adverse cardiac remodelling in a mouse model of pressure overload-induced cardiac hypertrophy?
Inhibition of miR-154 attenuates cardiac dysfunction and fibrosis in a mouse model of pressure overload, suggesting it as a potential therapeutic target for cardiac hypertrophy and remodeling.
miR-154 inhibition preserved function in overloaded mice; leaves open its role as a remodeling target pending human studies.
Expression of miR-154 is upregulated in the diseased heart and was previously shown to be upregulated in the lungs of patients with pulmonary fibrosis. However, the role of miR-154 in a model of sustained pressure overload-induced cardiac hypertrophy and fibrosis had not been assessed. To examine the role of miR-154 in the diseased heart, adult male mice were subjected to transverse aortic constriction for four weeks, and echocardiography was performed to confirm left ventricular hypertrophy and cardiac dysfunction. Mice were then subcutaneously administered a locked nucleic acid antimiR-154 or control over three consecutive days (25 mg/kg/day) and cardiac function was assessed 8 weeks later. Here, we demonstrate that therapeutic inhibition of miR-154 in mice with pathological hypertrophy was able to protect against cardiac dysfunction and attenuate adverse cardiac remodelling. The improved cardiac phenotype was associated with attenuation of heart and cardiomyocyte size, less cardiac fibrosis, lower expression of atrial and B-type natriuretic peptide genes, attenuation of profibrotic markers, and increased expression of p15 (a miR-154 target and cell cycle inhibitor). In summary, this study suggests that miR-154 may represent a novel target for the treatment of cardiac pathologies associated with cardiac fibrosis, hypertrophy and dysfunction.
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Bernardo et al. (2016) studied Cardiac hypertrophy and fibrosis (n=34). LNA-antimiR-154 vs. LNA-control or saline was evaluated on Fractional shortening (cardiac function). Therapeutic inhibition of miR-154 with LNA-antimiR-154 in mice with pressure overload-induced pathological hypertrophy protected against cardiac dysfunction, resulting in 33% higher fractional shortening compared to control.
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