Key result
Severe pulmonary regurgitation was associated with significantly lower expression of β2-AR and GRK2 in peripheral blood mononuclear cells compared to healthy controls, which normalized after pulmonary valve replacement.
Why the study?
Expression of β-adrenoceptors and GRKs in peripheral blood mononuclear cells changes with hemodynamic alterations, suggesting they could serve as potential biomarkers in pulmonary regurgitation.
Does pulmonary valve replacement improve the expression of β2-AR and GRK2 in PBMC in patients with severe pulmonary regurgitation?
Observational (n=45)
No
Does pulmonary valve replacement improve the expression of β2-AR and GRK2 in PBMC in patients with severe pulmonary regurgitation?
The expression of β2-AR and GRK2 in PBMC is reduced in patients with severe pulmonary regurgitation and normalizes after pulmonary valve replacement, suggesting their potential utility as biomarkers for clinical decision-making.
Hypothesis-generating for β-adrenergic biomarkers in pulmonary regurgitation; leaves open validation in prospective cohorts before any clinical role.
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 (478.0 ± 201.6 mRNA copies) vs. controls (812.6 497.23 mRNA copies), so as GRK2 expression (503.4 364.95 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.
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Serrano et al. (2019) conducted an observational in Severe pulmonary regurgitation (n=45). Severe pulmonary regurgitation vs. Healthy volunteers was evaluated on β2-AR expression in peripheral blood mononuclear cells (mRNA copies) (p=<0.05). Severe pulmonary regurgitation was associated with significantly lower expression of β2-AR and GRK2 in peripheral blood mononuclear cells compared to healthy controls, which normalized after pulmonary valve replacement.
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