Abstract
The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of beta-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.
Highlights
Heart failure (HF) is a significant health problem worldwide and despite many recent advances in treatment, HF-related morbidity and mortality remain elevated [1]
Advances in the knowledge of specific molecular characteristics and adaptations of the adrenergic system have permitted a better understanding of its role in the development and progression of heart failure [6]
SS-AR signaling and differences between ß-AR subtypes are important for the understanding of adrenergic system function. Both ß1 and ß2 subtypes are coupled to Gs protein, which stimulates adenylyl cyclases, resulting in the conversion of ATP to cAMP, which in turn binds to regulator subunits of protein kinase-A (PKA) and phosphorylation of a number of target intracellular proteins
Summary
Heart failure (HF) is a significant health problem worldwide and despite many recent advances in treatment, HF-related morbidity and mortality remain elevated [1]. Several experimental and clinical studies have demonstrated that this sustained adrenergic drive can be deleterious to the failing heart, contributing to HF progression, perpetuation and presentation [2]. This concept has been confirmed by the benefits of ß-blockers in patients with heart failure [3,4,5]. Advances in the knowledge of specific molecular characteristics and adaptations of the adrenergic system have permitted a better understanding of its role in the development and progression of heart failure [6]
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