Nayak Aditi, Neill Colin, Kormos Robert L, Lagazzi Luigi, Halder Indrani, McTiernan Charles, Larsen Jennifer, Inashvili Ana, Teuteberg Jeffrey, Bachman Timothy N, Hanley-Yanez Karen, McNamara Dennis M, Simon Marc A
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Heart Lung Transplant. 2017 Jun;36(6):657-665. doi: 10.1016/j.healun.2016.12.007. Epub 2016 Dec 23.
Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF.
Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR Array; Qiagen). Results were expressed as polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β-microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT).
CCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort.
Pre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.
右心室衰竭（RVF）使9%至44%的左心室辅助装置（LVAD）植入患者术后出现并发症。目前的预测评分在验证研究中的表现一般，且未纳入免疫标志物。趋化因子是炎症信号分子，在心脏生理学和应激适应中起重要作用。在本研究中，我们调查了发生RVF的LVAD接受者中趋化因子受体的调节情况。
检测111例LVAD患者植入前24小时采集的外周血中趋化因子受体（CCR）基因3至8的表达。使用PAXgene方案分离RNA。使用靶向微阵列（RT2 Profiler PCR Array；Qiagen）评估基因表达。结果以达到阈值的聚合酶链反应（PCR）循环数表示，并根据3个对照基因（甘油醛-3-磷酸脱氢酶（GAPDH）、次黄嘌呤磷酸核糖转移酶1（HPRT1）和β-微球蛋白（B2M））的平均值进行标准化。研究的次要结局为1年死亡率和长期右心室衰竭（RVF-LT）。
发生RVF的LVAD接受者中CCR3、CCR4、CCR6、CCR7和CCR8表达下调。在该患者队列中，需要右心室机械支持的患者CCR4、CCR7和CCR8进一步下调。此外，即使在调整RVF后，CCR3至CCR8的低表达仍与1年死亡率增加独立相关。在我们的患者队列中，CCR表达不能预测RVF-LT。
LVAD植入前CCR下调与RVF及植入后死亡率增加相关。炎症特征可能在该患者群体的预后中起主要作用。
