Abstract
Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Three different GRK isoforms (GRK2, GRK5, and GRK3) and two β-adrenoceptors (β1-AR and β2-AR) are present in peripheral blood mononuclear cells (PBMC) and their expression changes as a consequence of the hemodynamic and neurohumoral alterations that occur in some cardiovascular diseases. Therefore, they could be useful as biomarkers in PR. A prospective study was conducted to describe the expression (TaqMan Gene Expression Assays) of β-ARs and GRKs in PBMC isolated (Ficoll® gradient) from patients with severe PR before and after pulmonary valve replacement and establish if this expression correlates to clinical status. 23 patients with severe PR were included and compared with 22 healthy volunteers (controls). PR patients before the PVR had a significantly lower expression of β2-AR (513.8 ± 261.2 mRNA copies) vs. controls (812.5 ± 497.2 mRNA copies), so as GRK2 expression (503.4 ± 364.9 copies vs. 858.1 ± 380.3 mRNA copies). The expression of β2-AR and GRK2 significantly decreases in symptomatic and asymptomatic patients, as well as in patients under treatment with beta-blockers and non-treated patients. The expression of β2-AR and GRK2 in PR patients recovers the normal values after pulmonary valve replacement (754,8 ± 77,1 and 897,8 ± 87,4 copies, respectively). Therefore, changes in the expression of β2-AR and GRK2 in PBMC of PR patients, could be considered as potential biomarkers to determine clinical decisions.
Highlights
The β-adrenergic system plays a key role in the regulation of heart function and it is known that it is involved in the pathogenesis of heart failure (HF)
Levels of circulating catecholamines increase and this determines an adaptation in the expression and activity of adrenoceptors (AR) as well as the G-protein coupled receptors kinases (GRK), which phosphorylate AR when they are occupied by agonists
In a previous work we have found that the gene expression pattern of GRK2 and the β2-AR was altered in patients with severe Pulmonary regurgitation (PR) in a similar way to patients with advanced HF (Rodríguez-Serrano et al, 2018)
Summary
The β-adrenergic system plays a key role in the regulation of heart function and it is known that it is involved in the pathogenesis of heart failure (HF) In this pathology, levels of circulating catecholamines increase and this determines an adaptation in the expression and activity of adrenoceptors (AR) as well as the G-protein coupled receptors kinases (GRK), which phosphorylate AR when they are occupied by agonists. Changes in the expression of GRKs and β-ARs were determined in myocytes (endomyocardial biopsies, cardiac explant), but it is possible to study these changes in PBMC (Iaccarino et al, 2005; Agüero et al, 2008; Oliver et al, 2010) Their determination in peripheral blood can become a useful parameter for the follow-up of cardiovascular disease. In the study of HF, the expression of GRK2 in circulating lymphocytes (Rengo et al, 2016) has been used as a molecular marker
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