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, in 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.
Article: Inhibition of p38-alpha MAPK rescues cardiomyopathy induced by overexpressed beta2-adrenergic receptor, but not beta1-adrenergic receptor
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
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