GRK2 as a therapeutic target for heart failure

Alessandro Cannavo, Klara Komici, Leonardo Bencivenga, Maria Loreta D'amico, Giuseppina Gambino, Daniela Liccardo, Nicola Ferrara, Giuseppe Rengo

Research output: Contribution to journalReview articlepeer-review

Abstract

INTRODUCTION: G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of GPCRs, in particular β-adrenergic receptors (ARs), and as demonstrated by decades of investigation, it has a pivotal role in the development and progression of cardiovascular disease, like heart failure (HF). Indeed elevated levels and activity of this kinase are able to promote the dysfunction of both cardiac and adrenal α- and β-ARs and to dysregulate other protective signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent discoveries suggest that GRK2 can signal independently from GPCRs, in a 'non-canonical' manner, via interaction with non-GPCR molecule or via its mitochondrial localization. Areas covered: Based on this premise, GRK2 inhibition or its genetic deletion has been tested in several disparate animal models of cardiovascular disease, showing to protect the heart from adverse remodeling and dysfunction. Expert opinion: HF is one of the leading cause of death worldwide with enormous health care costs. For this reason, the identification of new therapeutic targets like GRK2 and strategies such as its inhibition represents a new hope in the fight against HF development and progression. Herein, we will update the readers about the 'state-of-art' of GRK2 inhibition as a potent therapeutic strategy in HF.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalExpert Opinion on Therapeutic Targets
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Drug Design
  • G-Protein-Coupled Receptor Kinase 2/antagonists & inhibitors
  • Gene Deletion
  • Heart Failure/drug therapy
  • Humans
  • Molecular Targeted Therapy

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