Lu Qun, Zhang Ruo-Chen, Chen Shu-Ping, Li Tao, Wang Ya, Xue Yan-Bo, Liu Jing, Han Xiu, Su Yi-Dan, Bai Ling, Du Xiao-Jun, Ma Ai-Qun
Department of Cardiovascular Medicine, First Affiliated Hospital, School of Medicine of Xi'an Jiaotong University, Xi'an, China.
Department of Cardiovascular Medicine, Xi'an Central Hospital, Xi'an, China.
Front Cardiovasc Med. 2021 Dec 22;8:748875. doi: 10.3389/fcvm.2021.748875. eCollection 2021.
The aim of present study is to evaluate the diagnostic and prognostic value of plasma galectin 3 (Gal-3) for HF originating from different causes. We investigated the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either β2- adrenergic receptor (β2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were examined in this study. All these patients were treated according to the Chinese HF guidelines of 2014; subsequently, they were followed up for 50 months, and we analyzed the prediction value of baseline Gal-3 to endpoints in these patients. Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often formed aggregates in Mst1-TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in β2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it was more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1-TG mice. However, plasma Gal-3 was higher in β2-AR TG mice than in nTG mice. In the cohort of HFrEF patients, the median plasma Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to Gal-3 levels. Patients with Gal-3 concentrations above the median were older, and had lower plasma hemoglobin, but higher plasma creatinine, tissue inhibitor of metalloproteinases 1 (TIMP-1), left ventricular end systolic diameter (LVESD), left ventricular end-systolic volumes (LVESV) and end-diastolic, as well as left ventricular end-diastolic volumes (LVEDV). Spearman correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 ( = 0.396, < 0.001), LVESV ( = 0.181, = 0.020) and LVEDV ( = 0.190, = 0.015). The 50-month clinical follow-up revealed 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients. Although plasma Gal-3 is associated with TIMP-1 and echocardiographic parameters, the diagnostic and prognostic value of Gal-3 in HFrEF is determined by the etiology of HF.
本研究的目的是评估血浆半乳糖凝集素3（Gal-3）对不同病因所致心力衰竭的诊断和预后价值。在本研究中，我们调查了两种转基因（TG）小鼠品系中心肌细胞特异性过表达β2-肾上腺素能受体（β2-AR TG）或哺乳动物 sterile 20样激酶1（Mst1-TG）的血浆Gal-3水平及心脏组织中的表达情况。此外，本研究还对陕西省两家医院的166例射血分数降低的心力衰竭（HFrEF）患者进行了检查。所有这些患者均按照2014年中国心力衰竭指南进行治疗；随后，对他们进行了50个月的随访，并分析了基线Gal-3对这些患者终点事件的预测价值。Gal-3定位于心肌细胞的细胞质和细胞核中，在Mst1-TG小鼠中常形成聚集体。在Mst1-TG心脏中，细胞外Gal-3染色不常见。然而，在β2-AR TG小鼠中，尽管Gal-3也在心肌细胞中表达，但在间质细胞（如成纤维细胞和巨噬细胞）中表达更高。正常转基因（nTG）小鼠和Mst1-TG小鼠的血浆Gal-3水平相当。然而，β2-AR TG小鼠的血浆Gal-3水平高于nTG小鼠。在HFrEF患者队列中，血浆Gal-3浓度中位数为158.42 pg/mL。所有参与者根据Gal-3水平分为两组。Gal-3浓度高于中位数的患者年龄较大，血浆血红蛋白水平较低，但血浆肌酐、金属蛋白酶组织抑制剂1（TIMP-1）、左心室收缩末期内径（LVESD）、左心室收缩末期容积（LVESV）和舒张末期左心室舒张末期容积（LVEDV）较高。Spearman相关性分析显示，Gal-3与TIMP-1（r = 0.396，P < 0.001）、LVESV（r = 0.181，P = 0.020）和LVEDV（r = 0.190，P = 0.015）呈正相关。50个月的临床随访显示有43例死亡、97例非计划再次住院和111例复合终点事件。Cox分析表明，尽管Gal-3在全心力衰竭患者或冠心病（CHD）患者中均未提供任何预后价值，但在非CHD患者中确实提供了预后价值。尽管血浆Gal-3与TIMP-1和超声心动图参数相关，但Gal-3在HFrEF中的诊断和预后价值取决于心力衰竭的病因。
