Beta-arrestin: a signaling molecule and potential therapeutic target for heart failure. J Mol Cell Cardiol

Duke University School of Medicine, Durham, NC, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 4.66). 11/2010; 51(4):534-41. DOI: 10.1016/j.yjmcc.2010.11.005
Source: PubMed


Currently, some of the most effective treatments for heart failure target GPCRs such as the beta-adrenergic receptors (β1AR and β2AR) and angiotensin II type IA receptors (AT1aR). Ligands for these receptors not only function by blocking the deleterious G-protein mediated pathway leading to heart failure, but also signal via G-protein independent pathways that involve receptor phosphorylation by G-protein receptor kinases (GRKs) leading to recruitment of the multifunctional protein, β-arrestin. Originally thought to play a role in GPCR desensitization and internalization, β-arrestin has recently been shown to mediate signaling independent of classical second messengers in a way that is often protective to the heart. The multi-functionality of β-arrestin makes it an intriguing molecule in the development of the next generation of drugs for cardiac diseases with the potential to simultaneously inhibit deleterious G-protein dependent pathways while activating beneficial β-arrestin mediated signaling. In this review, we explore various facets of β-arrestin signaling and offer a perspective on its potential role as a key signaling molecule in the treatment of heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

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    • "However, βarrs do not merely terminate G protein-mediated signaling by GPCRs. It is now well established that they promote signaling in their own right, independently of G proteins, and a number of recent studies point to a beneficial role played by them in the heart, especially when they engage the cardiac β1AR.99 More specifically, they have been reported to mediate epidermal growth factor receptor (EGFR) transactivation by the β1AR.99 "
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    • "An initial bradycardia and a delayed development of the tachycardia were seen in desipramine-treated SHR. This observation suggested that increased βAR activation hampered the positive chronotropic response to norepinephrine release, in agreement with that excessive signaling may hamper cardiac function (Noor et al., 2010). A negative chronotropic effect due to β3AR-activity did not influence the HR-response to 4-AP in either strain, although the β3AR antagonist SR59230A, as in previous studies (Berg et al., 2010), increased resting HR in WKY but not SHR. "
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