Khirfan Ghaleb, Li Manshi, Wang Xiaofeng, DiDonato Joseph A, Dweik Raed A, Heresi Gustavo A
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, OH, USA.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
Pulm Circ. 2021 Apr 22;11(2):20458940211010371. doi: 10.1177/20458940211010371. eCollection 2021 Apr-Jun.
Recent studies have shown low high-density lipoprotein cholesterol (HDL-C) and dysregulated lipid metabolism in chronic thromboembolic pulmonary hypertension (CTEPH). Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-C and mediates most of its functions. We hypothesize that ApoA-1 and its oxidative state might be more sensitive biomarkers in CTEPH. Plasma levels of HDL-C, ApoA-I, paraoxonase-1 enzyme activity (PON1), and the oxidized dysfunctional ApoA-I (oxTrp72-ApoA-I) were measured in patients with CTEPH and compared to those in healthy controls. Association with markers of disease severity in CTEPH was assessed. We included a total of 61 patients with CTEPH (age: 61.2 ± 15 years; male 52.5%) and 28 control subjects (age: 60.1 ± 8 years; male 59.3%). When adjusting for age, sex, body mass index, and statin use, ApoA-I was lower in CTEPH compared to controls (CTEPH:125.2 ± 27 mg/dl; control:158.3 ± 29.4 mg/dl; < 0.001), but HDL-C levels were not statistically different. There were no significant differences in PON and oxTrp72-ApoA-I/ApoA-I ratio. In exploratory analyses, ApoA-I was associated with mean right atrial pressure (r = -0.32, = 0.013) and N-terminal pro B-type natriuretic peptide (r = -0.31, = 0.038). There were no significant associations between HDL-C, PON1, or oxTrp72-ApoA-I/ApoA-I ratio and markers of disease severity. We conclude that ApoA-I is a more sensitive biomarker than HDL-C in CTEPH, and may be associated with right heart dysfunction.
近期研究表明，慢性血栓栓塞性肺动脉高压（CTEPH）患者存在高密度脂蛋白胆固醇（HDL-C）水平降低及脂质代谢失调的情况。载脂蛋白A-I（ApoA-I）是HDL-C的主要蛋白质成分，并介导其大部分功能。我们推测，ApoA-1及其氧化状态可能是CTEPH中更敏感的生物标志物。我们检测了CTEPH患者血浆中HDL-C、ApoA-I、对氧磷酶-1（PON1）酶活性以及氧化功能失调的ApoA-I（oxTrp72-ApoA-I）水平，并与健康对照者进行比较。评估了其与CTEPH疾病严重程度标志物的相关性。我们共纳入了61例CTEPH患者（年龄：61.2±15岁；男性占52.5%）和28例对照者（年龄：60.1±8岁；男性占59.3%）。在对年龄、性别、体重指数和他汀类药物使用情况进行校正后，CTEPH患者的ApoA-I水平低于对照组（CTEPH组：125.2±27mg/dl；对照组：158.3±29.4mg/dl；P<0.001），但HDL-C水平无统计学差异。PON和oxTrp72-ApoA-I/ApoA-I比值无显著差异。在探索性分析中，ApoA-I与平均右心房压（r=-0.32，P=0.013）及N端前脑钠肽（r=-0.31，P=0.038）相关。HDL-C、PON1或oxTrp72-ApoA-I/ApoA-I比值与疾病严重程度标志物之间无显著相关性。我们得出结论，在CTEPH中，ApoA-I是比HDL-C更敏感的生物标志物，且可能与右心功能不全有关。
