吲哚胺2,3双加氧酶(IDO),色氨酸(Trp)降解的犬尿氨酸(Kyn)途径中的限速酶,受炎症调节,被认为是驱动免疫耐受和免疫抑制机制的关键分子。对活动性冠状动脉疾病(CAD)患者的IDO活性知之甚少。
我们前瞻性招募了计划进行冠状动脉造影的患者。IDO的测量,高敏肌钙蛋白T(hs-TnT),和高敏C反应蛋白(hs-CRP)水平在基线进行,并在6个月随访时监测IDO活性.
纳入了三百零五名患者。98例患者(32.1%)出现近期急性冠状动脉综合征(ACS)。IDO的显著差异,犬尿氨酸,和hs-TnT在有和无显著CAD的患者之间观察到。基线IDO活动,犬尿氨酸水平,和hs-TnT水平均显著高于3血管的显著CAD患者,2船,和1血管参与比那些无关紧要的CAD[(0.17、0.13和0.16vs.0.03;p=0.003),(5.89、4.58和5.24vs.2.74µM/g,分别为;p=0.011),和(18.27、12.22和12.86vs.10.89mg/dL,分别;p<0.001)]。一年死亡率为3.9%。当我们比较存活的病人和死亡的病人时,通过冠状动脉造影,我们发现左主干(LM)疾病的患病率显着降低(6.1%vs.33.3%,p=0.007),以及更高基线犬尿氨酸的趋势(5.07vs.0.79µM/g,p=0.082)和更高的IDO(0.15与0.02,p=0.081)在存活的患者中。
CAD患者通过IDO功能介导的免疫代谢反应得到增强,并与疾病的范围和严重程度相关。LM病患者1年死亡率较高。较低级别的IDO,正如IDO反应不足所表明的那样,显示出预测1年死亡率的趋势。试验注册TCTR试验注册编号TCTR20200626001。注册日期2020年6月26日。\"追溯注册\"。
Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in the kynurenine (Kyn) pathway of tryptophan (Trp) degradation, is modulated by inflammation, and is regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. Little is known about IDO activity in patients with active coronary artery disease (CAD).
We prospectively enrolled patients who were scheduled to undergo coronary angiography. Measurement of IDO, high-sensitivity troponin T (hs-TnT), and high-sensitivity C-reactive protein (hs-CRP) levels was performed at baseline, and IDO activity was monitored at the 6-month follow-up.
Three hundred and five patients were enrolled. Ninety-eight patients (32.1%) presented with recent acute coronary syndrome (ACS). Significant difference in IDO, kynurenine, and hs-TnT between patients with and without significant CAD was observed. Baseline IDO activity, kynurenine level, and hs-TnT level were all significantly higher in significant CAD patients with 3-vessel, 2-vessel, and 1-vessel involvement than in those with insignificant CAD [(0.17, 0.13, and 0.16 vs. 0.03, respectively; p = 0.003), (5.89, 4.58, and 5.24 vs. 2.74 µM/g, respectively; p = 0.011), and (18.27, 12.22, and 12.86 vs. 10.89 mg/dL, respectively; p < 0.001)]. One-year mortality was 3.9%. When we compared between patients who survived and patients who died, we found a significantly lower prevalence of left main (LM) disease by coronary angiogram (6.1% vs. 33.3%, p = 0.007), and also a trend toward higher baseline kynurenine (5.07 vs. 0.79 µM/g, p = 0.082) and higher IDO (0.15 vs. 0.02, p = 0.081) in patients who survived.
Immunometabolic response mediated via IDO function was enhanced in patients with CAD, and correlated with the extent and severity of disease. Patients with LM disease had higher 1-year mortality. Lower level of IDO, as suggested by inadequate IDO response, demonstrated a trend toward predicting 1-year mortality. Trial registration TCTR Trial registration number TCTR20200626001. Date of registration 26 June 2020. \"Retrospectively registered\".