title: GRK2 as negative modulator of NO bioavailability: Implications for cardiovascular disease.
abstract: Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability. This review, will explore the specific interrelation between βARs, GRK2 and NO in the cardiovascular system and their inter-relationship for the pathogenesis of the onset of disease. Last, we will update the readers on the current status of GRK2 inhibitors as a potential therapeutic strategy for heart failure with an emphasis on their ability of rescuing NO bioavailability.
authors.affiliation: Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cannavo
authors.affiliation: Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA. Electronic address: walter.koch@temple.edu.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: Cardiovascular system; G protein-coupled receptor kinase; Nitric oxide; β-adrenergic receptor