Role of β-adrenergic receptor signaling and desensitization in heart failure: new concepts and prospects for treatment

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The use of β-blockers to antagonize β-adrenergic receptor signaling in the heart has become a standard method of treatment for heart failure, resulting in positive clinical outcomes alone and in conjunction with other modulators of cardiomyocyte contractility. However, an entire explanation for improved cardiac function in patients using β-blockers is unknown, and in fact may be quite complicated, considering the numerous intracellular signaling pathways associated with β-adrenergic receptors. Stimulation of β-adrenergic receptors during both normal conditions and during heart failure activate several distinct signaling cascades, which influence cardiomyocyte contraction, hypertrophy and apoptosis. This review explores the signaling cascades induced by β-adrenergic receptor activation in normal and desensitized states to provide new insight into the effective treatment of cardiac dysfunction.

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