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RESEARCH PRODUCT

Myocardial G Protein Receptor–Coupled Kinase Expression Correlates With Functional Parameters and Clinical Severity in Advanced Heart Failure

Luis AlmenarFermí MontóDiana VicenteLuis Martínez DolzEduardo OliverJaime AgüeroIgnacio Sánchez-lázaroAntonio SalvadorPilar D'oconJoaquín Rueda

subject

G-Protein-Coupled Receptor Kinase 5Malemedicine.medical_specialtyG-Protein-Coupled Receptor Kinase 2Down-RegulationPolymerase Chain ReactionSeverity of Illness IndexGene Expression Regulation EnzymologicInternal medicinemedicineHumansRNA MessengerRegistriesReceptorG protein-coupled receptorHeart FailureG protein-coupled receptor kinasebiologybusiness.industryMyocardiumBeta adrenergic receptor kinaseStroke volumeMiddle AgedG-Protein-Coupled Receptor Kinasesmedicine.diseaseTransplantationEndocrinologySpainHeart failureCirculatory systembiology.proteinFemaleHeart-Assist DevicesCardiology and Cardiovascular Medicinebusiness

description

In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial β-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale.We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples.In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in β-agonist-treated patients (vs β-blockers: P.05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P.05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings.Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.

yearjournalcountryeditionlanguage
2010-12-10Journal of Cardiac Failure
https://doi.org/10.1016/j.cardfail.2011.10.008