Rodriguez-Serrano María, Rueda Joaquín, Buendía Francisco, Monto Fermi, Aguero Jaime, Osa Ana, Cano Oscar, Martínez-Dolz Luis, D'Ocon Pilar
Servicio de Cardiología, Hospital de Manises, Valencia, Spain.
Servicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Front Pharmacol. 2019 Feb 19;10:93. doi: 10.3389/fphar.2019.00093. eCollection 2019.
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.
肺动脉反流（PR）是先天性心脏病修复术后常见的并发症。外周血单核细胞（PBMC）中存在三种不同的G蛋白偶联受体激酶（GRK）亚型（GRK2、GRK5和GRK3）和两种β-肾上腺素能受体（β1-AR和β2-AR），在某些心血管疾病发生时，其表达会因血流动力学和神经体液改变而发生变化。因此，它们可能作为PR的生物标志物。进行了一项前瞻性研究，以描述重度PR患者在肺动脉瓣置换术前和术后分离的PBMC（Ficoll梯度法）中β-ARs和GRKs的表达（TaqMan基因表达分析），并确定这种表达是否与临床状态相关。纳入了23例重度PR患者，并与22名健康志愿者（对照组）进行比较。PVR术前PR患者的β2-AR表达（513.8±261.2 mRNA拷贝）显著低于对照组（812.5±497.2 mRNA拷贝），GRK2表达也是如此（503.4±364.9拷贝对858.1±380.3 mRNA拷贝）。有症状和无症状患者以及接受β受体阻滞剂治疗的患者和未治疗患者中，β2-AR和GRK2的表达均显著降低。PR患者在肺动脉瓣置换术后，β2-AR和GRK2的表达恢复到正常值（分别为754.8±77.1和897.8±87.4拷贝）。因此，PR患者PBMC中β2-AR和GRK2表达的变化可被视为决定临床决策的潜在生物标志物。
