Adrenergic signalling affects progression of cardiomyopathy
-adrenergic receptor signalling or excitation-contraction coupling can prevent systolic dysfunction, exercise intolerance and cardiac remodelling.
In the course of chronic heart failure myocytes demonstrate changes in β-adrenergic receptor (βAR) signalling that impair cardiac contractility, but the role of these abnormalities in the progression of the disease is unknown. In 15 April Journal of Clinical Investigation Kalev Freeman and colleagues from the University of Colorado, report a transgenic manipulation of βAR that had distinct effects on disease progression.
Freeman et al tested different manipulations of the βAR in a murine model of hypertrophic cardiomyopathy. They found that high-level over expression of the β2AR enhanced cardiac function at early time points, but ultimately resulted in severe heart failure, increased mortality, extreme cardiac dilation and fibrosis. Phospholamban ablation prevented systolic dysfunction and exercise intolerance, but not hypertrophy. Cardiac expression of a peptide inhibitor of the βAR kinase 1 not only prevented systolic dysfunction and exercise intolerance but also decreased cardiac remodelling and hypertrophic gene expression (J Clin Invest 2001, 107:967-974).
This suggests that selective modulation of βAR signalling may be beneficial for cardiomyopathy and βARK1 protein may represent a therapeutic target with significant potential for preventing the progression of heart failure.