Laboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Laboratory of Molecular and Cellular Pathology and Gene Diagnostics, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Gene. 2022 Nov 30;844:146820. doi: 10.1016/j.gene.2022.146820. Epub 2022 Aug 17.
β1-adrenergic receptors (β1-AR) directly affect on intracardiac hemodynamic and the ability of the heart to tolerate physical activity by regulating its inotropic and chronotropic functions. Severe hypersympathicotonia, specific to coronary artery disease (CAD) and chronic heart failure (HF), leads to impaired functioning of β1-AR. The aim of this research was to assess the expression level of the β1-AR ADRB1 gene in the myocardium, to evaluate the β-adrenergic reactivity of the membrane (β-ARM) of erythrocytes, and to analyze the association of these parameters with myocardial contractile dysfunction in patients with a myocardial infarction (MI) in the past and without it. The study included 126 patients with chronic CAD. Among the patients, 55.6 % had a history of MI at least 6 months ago. The expression of the ADRB1 gene was assessed using real-time polymerase chain reaction. With this purpose, we isolated RNA from the right atrial appendage, which was excised when a heart-lung machine was connected during a planned coronary bypass surgery. β-ARM was evaluated in 57 patients. This method is based on the fact of inhibition of hemolysis of erythrocytes, placed in a hyposmotic medium, in the presence of a β-blocker. Within the whole sample of patients, the expression of the ADRB1 gene is comparable in different functional classes of HF. There was no linear correlation between the expression of the ADRB1 gene and left ventricle ejection fraction (LVEF). In patients with a history of MI, the expression of the ADRB1 gene was elevated when compared to a group of patients without MI (p = 0.017). Patients with a history of MI had higher values of β-ARM than those without MI (p = 0.017). The reverse correlation between β-ARM and LVEF (r = -0,570, p = 0,002) was revealed in the group of patients without MI but not in the group of patients with a history of MI (r = -0,137, p = 0,479). In the sample of patients with chronic CAD, in the myocardium of subjects with a history of MI, the relative expression of ADRB1 gene was higher compared to the group of patients without MI. In patients with different functional classes (FC) of HF and with different ejection fraction, both with MI and without it, ADRB1 gene expression was comparable. In the group of patients with a history of MI, an increase in β-ARM was observed, i.e. decrease in the number or sensitivity of β-AR. Among patients without MI, an inverse correlation was found between β-ARM and LVEF.
β1-肾上腺素能受体（β1-AR）通过调节其变力和变时功能，直接影响心脏的室内血流动力学和对体力活动的耐受能力。特发性冠状动脉疾病（CAD）和慢性心力衰竭（HF）导致的严重交感神经过度兴奋，导致β1-AR 功能障碍。本研究旨在评估心肌中β1-AR ADRB1 基因的表达水平，评估红细胞膜（β-ARM）的β-肾上腺素能反应性，并分析这些参数与过去和没有心肌梗死（MI）的患者心肌收缩功能障碍的相关性。研究纳入了 126 例慢性 CAD 患者。其中 55.6%的患者至少在 6 个月前有 MI 病史。使用实时聚合酶链反应评估 ADRB1 基因的表达。为此，我们从右心房附件中提取 RNA，当计划进行冠状动脉旁路手术时，体外循环机会连接右心房附件。在 57 例患者中评估了β-ARM。该方法基于在低渗介质中存在β-阻滞剂时抑制红细胞溶血的事实。在整个患者样本中，不同 HF 功能分类的 ADRB1 基因表达无差异。ADRB1 基因的表达与左心室射血分数（LVEF）之间没有线性相关性。与无 MI 组相比，有 MI 病史的患者 ADRB1 基因的表达升高（p=0.017）。有 MI 病史的患者β-ARM 值高于无 MI 病史的患者（p=0.017）。在无 MI 病史的患者组中发现了β-ARM 与 LVEF 之间的负相关（r=-0.570，p=0.002），但在有 MI 病史的患者组中没有发现（r=-0.137，p=0.479）。在慢性 CAD 患者样本中，与无 MI 组相比，有 MI 病史的患者心肌中 ADRB1 基因的相对表达更高。在具有不同 HF 功能分类（FC）和不同射血分数的患者中，无论是否有 MI，ADRB1 基因表达都相似。在有 MI 病史的患者组中，β-ARM 增加，即β-AR 的数量或敏感性下降。在无 MI 病史的患者中，发现β-ARM 与 LVEF 呈负相关。
