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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Therapeutic potential of G-protein coupled receptor kinases in the heart.

The actions of G-protein coupled receptor kinases (GRKs) critically regulate beta-adrenergic receptor (betaAR) signalling. In the cardiovascular system, the betaAR signalling pathway controls important responses of the heart such as the ability to contract (inotropy), the ability to contract faster (chronotropy) and the ability to relax (lusotropy). The observation that the betaAR kinase (betaARK1, also known as GRK2), the most abundant GRK in the heart, is increased in cardiovascular disease associated with impaired cardiac function, suggests that this molecule could have pathophysiological relevance in the setting of heart failure. Technological advances in the genetic engineering of mice have provided a powerful tool to study the physiological implications of altering GRK activity and expression in the heart. Recent studies have demonstrated that betaARK1 plays a key role in not only the regulation of myocardial signalling, but also in cardiac function and development. Importantly, targeting the activity of GRKs, and betaARK1 in particular, appears to represent a novel therapeutic strategy for the treatment of the failing heart. At present, gene therapy modalities are being tested which inhibit the activity of betaARK1 in the heart. This technology makes it possible to test directly whether betaARK1 inhibition in the setting of heart disease will improve the function of the compromised heart. Thus, these genetic approaches or the development of small molecule inhibitors of GRK activity, may lead to novel therapeutic approaches for cardiovascular disease.[1]


  1. Therapeutic potential of G-protein coupled receptor kinases in the heart. Iaccarino, G., Koch, W.J. Expert opinion on investigational drugs. (1999) [Pubmed]
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