Cyclophilin A as a biomarker for the therapeutic effect of balloon angioplasty in chronic thromboembolic pulmonary hypertension.
Cyclophilin A as a biomarker for the therapeutic effect of balloon angioplasty in chronic thromboembolic pulmonary hypertension.
复制标题
亲环蛋白 A 作为球囊血管成形术治疗慢性血栓栓塞性肺动脉高压的生物标志物。
DOI：
10.1016/j.jjcc.2019.09.010
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发表时间：
2020
期刊：
影响因子：
2.5
通讯作者：
Shimokawa H.
中科院分区：
文献类型：
--
作者：
Kozu K;Satoh K;Aoki T;Tatebe S;Miura M;Yamamoto S;Yaoita N;Suzuki H;Shimizu T;Sato H;Konno R;Terui Y;Nochioka K;Kikuchi N;Satoh T;Sugimura K;Miyata S;Shimokawa H.
背景尽管在慢性血栓栓塞性肺动脉高压（CTEPH）患者中，球囊肺血管成形术（BPA）后心脏肌钙蛋白和利钠肽降低，右心室后负荷改善，但评估BPA独立于心力衰竭状态的影响的生物标志物仍有待开发。我们证实CyPA是由肺血管平滑肌细胞在机械牵拉和缺氧时分泌的。结果CTEPH患者CyPA水平升高，（12.7，IQR：7.6-16.0）与8例有静脉血栓栓塞病史的血栓栓塞对照相比（4.9，IQR：2.4-11.2）和18名健康对照者（4.1，IQR：2.4-6.8）（均P < 0.05），与平均肺动脉压（r= 0.50，p = 0.0003）和肺血管阻力（r= 0.32，p = 0.026）呈线性相关。BPA可降低CyPA水平，并有降低脑型利钠肽（BNP）水平的趋势（p< 0.01和p = 0.07）。在基线时BNP升高（≥35 pg/mL）和正常（<35 pg/mL）两个亚组中，BPA前后CyPA的变化比较，BNP升高组和BNP正常组CyPA均降低（均P < 0.05）。相反，BNP仅在BNP较高的患者中降低（p< 0.05）。此外，CyPA在低血糖患者中均降低，（<25公斤/平方米）及以上基线时体重指数（BMI）≥25 kg/m2（两者均< 0.05），而BPA倾向于降低BMI较低患者的BNP（p= 0.12），但BMI较高的人则不然结论CyPA可作为一个有用的生物标志物来评估BPA的影响，即使在正常BNP或高BMI的患者。
BackgroundAlthough cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed.MethodsIn 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia.ResultsCyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (bothp< 0.05) and were linearly correlated with mean pulmonary arterial pressure (r= 0.50,p= 0.0003) and pulmonary vascular resistance (r= 0.32,p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p< 0.01 andp= 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35 pg/mL) and normal (<35 pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (bothp< 0.05). In contrast, BNP decreased only in patients with higher BNP (p< 0.05). Also, CyPA decreased both in patients with lower (<25 kg/m2) and higher (≥25 kg/m2) body mass index (BMI) at baseline (bothp< 0.05), whereas BPA tended to reduce BNP in patients with lower BMI (p= 0.12) but not in those with higher BMI (p= 0.55).ConclusionsCyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.