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Modulating G Protein-Coupled Receptors to Effect Reverse Cardiac Remodeling

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

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Abstract

G protein-coupled receptors (GPCRs) represent the largest known family of transmembrane receptors and therapeutic targets in cardiovascular medicine, accounting for a large number of marketed cardiovascular pharmaceuticals. Traditionally, GPCR stimulation promotes G protein signaling and, to limit unrestrained stimulation, activation of G protein-coupled receptor kinases (GRKs), leading to agonist-dependent receptor phosphorylation. In turn, GPCR phosphorylation promotes β-arrestin binding to the receptors, which sterically prevents further G protein signaling and scaffold receptors to the internalization machinery. However, novel aspects of GPCR signaling have been recently appreciated, including G protein modulators, G protein-independent pathways, and GRK adrenal modulation of adrenergic drive. Since all currently used drugs have been developed using assays only testing G protein-dependent effects, the discovery of such novel signal transduction pathways might represent an important opportunity to identify additional therapeutic approaches to reverse or prevent cardiac remodeling and failure.

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Author information

Authors and Affiliations

  1. Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Via Pansini 5, 89131, Naples, Italy

    Cinzia Perrino M.D., Ph.D.

  2. Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Department of Medicine, Department of Cell Biology, Department of Molecular Genetics, Duke University Medical Center, Durham, NC, USA

    Howard A. Rockman

Authors
  1. Cinzia Perrino M.D., Ph.D.
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  2. Howard A. Rockman
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Corresponding author

Correspondence to Cinzia Perrino M.D., Ph.D. .

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Editors and Affiliations

  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Perrino, C., Rockman, H.A. (2013). Modulating G Protein-Coupled Receptors to Effect Reverse Cardiac Remodeling. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_10

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