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GRK2 as a therapeutic target for heart failure
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
G protein-coupled receptor
gene-therapy
GRK2
heart failure
Animals
Disease Models, Animal
Disease Progression
G-Protein-Coupled Receptor Kinase 2
Gene Deletion
Heart Failure
Humans
Molecular Targeted Therapy
Drug Design
Molecular Medicine
Pharmacology
Drug Discovery3003 Pharmaceutical Science
Clinical Biochemistry
Regulator
Disease
030204 cardiovascular system & hematology
Bioinformatics
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Drug Discovery
medicine
Receptor
biology
Sphingosine
business.industry
Animal
Beta adrenergic receptor kinase
medicine.disease
030104 developmental biology
chemistry
Heart failure
Disease Models
biology.protein
Signal transduction
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....647dbfe424f572e11e916ca2fc2a208c