Individuals with some forms of heart failure are treated with drugs that are known as beta-blockers because they target proteins known as beta-adrenergic receptors (beta-ARs).
Now, a potential alternative strategy to treating heart failure by targeting molecules downstream of beta-ARs is suggested by mouse studies conducted by researchers from the University of Medicine and Dentistry of New Jersey.
Mice overexpressing either beta1-AR or beta2-AR develop heart disease as they age. In the study, which appears online on April 19 in advance of publication in the May print issue of the Journal of Clinical Investigation, Dorothy Vatner and colleagues show that if mice overexpressing beta2-AR also express an inhibitor of the downstream signaling molecule p38-alpha MAPK (dominant-negative p38-alpha) they are protected from developing heart disease.
By contrast, mice overexpressing beta1-AR were not protected by the presence of dominant-negative p38-alpha, even though they exhibited increased p38-alpha expression. This study indicates that p38-alpha has an important role downstream of beta2-AR, but not beta1-AR, in development of heart disease. Other signaling molecules must therefore be activated downstream of beta1-AR, and the authors suggest that targeting the signaling molecules downstream of beta-ARs might provide a new approach to treating individuals with heart failure.