Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, Groningen, 9700 RB, The Netherlands.
Cardiovasc Drugs Ther. 2021 Oct;35(5):953-963. doi: 10.1007/s10557-020-06999-7.
Heart failure (HF) is considered to be a prothrombotic condition and it has been suggested that coagulation factors contribute to maladaptive cardiac remodelling via activation of the protease-activated receptor 1 (PAR1). We tested the hypothesis that anticoagulation with the factor Xa (FXa) inhibitor apixaban would ameliorate cardiac remodelling in rats with HF after myocardial infarction (MI).
Male Sprague-Dawley rats were either subjected to permanent ligation of the left ascending coronary artery (MI) or sham surgery. The MI and sham animals were randomly allocated to treatment with placebo or apixaban in the chow (150 mg/kg/day), starting 2 weeks after surgery. Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac hypertrophy were assessed in the left ventricle (LV). Apixaban resulted in a fivefold increase in anti-FXa activity compared with vehicle, but no overt bleeding was observed and haematocrit levels remained similar in apixaban- and vehicle-treated groups. After 10 weeks of treatment, LV ejection fraction was 42 ± 3% in the MI group treated with apixaban and 37 ± 2 in the vehicle-treated MI group (p > 0.05). Both vehicle- and apixaban-treated MI groups also displayed similar degrees of LV dilatation, LV hypertrophy and interstitial fibrosis. Histological and molecular markers for pathological remodelling were also comparable between groups, as was the activity of signalling pathways downstream of the PAR1 receptor.
FXa inhibition with apixaban does not influence pathological cardiac remodelling after MI. These data do not support the use of FXa inhibitor in HF patients with the aim to amend the severity of HF. Graphical Abstract.
心力衰竭（HF）被认为是一种促血栓形成的病症，有研究表明凝血因子通过激活蛋白酶激活受体 1（PAR1）导致适应性心脏重构。我们通过测试假设，即使用因子 Xa（FXa）抑制剂阿哌沙班进行抗凝治疗，是否可以改善心肌梗死后（MI）HF 大鼠的心脏重构。
雄性 Sprague-Dawley 大鼠接受左冠状动脉升支永久性结扎（MI）或假手术。MI 和假手术动物随机分配到在饲料中接受安慰剂或阿哌沙班（150mg/kg/天）治疗，手术后 2 周开始治疗。使用超声心动图评估心功能，并在左心室（LV）中评估心脏肥大的组织学和分子标志物。与载体相比，阿哌沙班导致抗 FXa 活性增加了五倍，但未观察到明显出血，并且阿哌沙班和载体治疗组的血细胞比容水平相似。经过 10 周的治疗后，接受阿哌沙班治疗的 MI 组的 LV 射血分数为 42±3%，而接受载体治疗的 MI 组为 37±2%（p>0.05）。载体和阿哌沙班治疗的 MI 组的 LV 扩张、LV 肥大和间质纤维化程度也相似。组织学和分子标志物用于病理性重塑的标志物在组间也具有可比性，PAR1 受体下游信号通路的活性也是如此。
阿哌沙班抑制 FXa 不会影响 MI 后病理性心脏重构。这些数据不支持 HF 患者使用 FXa 抑制剂来改善 HF 的严重程度。
图摘要。
