Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Valencia, Spain.
J Card Fail. 2012 Jan;18(1):53-61. doi: 10.1016/j.cardfail.2011.10.008. Epub 2011 Nov 25.
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.
在心力衰竭（HF）中，交感神经过度激活会导致心肌β肾上腺素能信号转导产生有害影响，受体下调和脱敏是由 G 蛋白偶联激酶（GRK）介导的。我们假设使用机构间机械循环辅助注册（INTERMACS）量表，GRK 同工型的变化可能与晚期 HF 的临床状况有关。
我们纳入了 31 名接受移植的晚期 HF 患者。根据 INTERMACS 图谱，分析并比较了左心室（LV）心肌中 GRK 同工型的 mRNA 和蛋白水平与非衰竭 LV 样本。
在衰竭的 LV 心肌中，与对照样本相比，GRK2 和 GRK5（但不是 GRK3）蛋白上调。在 HF 患者中，与β受体阻滞剂相比，β激动剂治疗的患者（P <.05）和 INTERMACS 风险较高的患者（谱 2 和 3 比谱 4 和 5：P <.05）中，GRK2 和 GRK5 的 mRNA 和蛋白丰度增加。GRK2 表达与 LV 射血分数呈显著负相关，支持了这些发现。
用 INTERMACS 量表和 LV 射血分数来表示，GRK2 的表达增加与临床严重程度相关，这表明其可能是晚期 HF 的一个潜在靶点。这些变化与衰竭心肌中 GRK5 的表达相平行，表明其在人类 HF 中具有重要作用。
