Departamento de Farmacología, Facultad de Farmacia, Universitat de València, Spain.
Am J Physiol Heart Circ Physiol. 2012 Aug 1;303(3):H368-76. doi: 10.1152/ajpheart.01061.2011. Epub 2012 Jun 8.
Downregulation of β(1)- adrenergic receptors (β(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α(1A), α(1B), α(1D), β(1), β(2), and β(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the α(1A)-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) β(1)-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC.
β(1)-肾上腺素能受体（β(1)-ARs）的下调和 G 蛋白偶联受体激酶 2（GRK2）的表达/功能增加已在人类心力衰竭中观察到，但其他 AR 和 GRK 的表达变化尚未确定。另一个未解决的问题是这些代偿机制的发生率取决于心力衰竭的病因和治疗。为了分析这些问题，我们定量分析了 6 种 AR（α(1A)、α(1B)、α(1D)、β(1)、β(2)和β(3)）和 3 种 GRK（GRK2、GRK3 和 GRK5）在左心室（LV）和右心室（RV）中的 mRNA/蛋白表达，来自四个供体，10 名缺血性心肌病（IC）患者，14 名扩张型心肌病（DC）患者和 10 名非缺血性、非扩张性心脏病（NINDC）患者。我们将 AR 和 GRK 的表达变化与左心室射血分数（LVEF）和左心室收缩末期和左心室舒张末期直径（LVESD 和 LVEDD）等临床变量相关联。主要发现包括：1）LV 中的 α(1A)-AR 表达与 LVEF 呈正相关；2）GRK3 和 GRK5 的表达与 LVESD 和 LVEDD 呈负相关，支持先前关于这两种激酶在衰竭心脏中具有保护作用的观察结果；3）IC 的 LV 和 RV、DC 的 LV 和 NINDC 的 RV 中β(1)-AR 表达下调。与在 IC 中未观察到的 GRK2 的表达增加（IC 中未观察到）相比，这种差异决定了 IC 和 DC 与 NINDC 相比，LVEF 更低。
