Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
Clin Transplant. 2021 Jan;35(1):e14133. doi: 10.1111/ctr.14133. Epub 2020 Nov 20.
Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients.
We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and O-H O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death.
We found consistent differences in two proteins involved in cholesterol homeostasis: significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p < .05) and significantly decreased paraoxonase 3 (PON3) (p < .05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p < .05) and borderline significantly increased in patients experiencing major adverse cardiac events (p = .10) and patients with macrovascular CAV (p = .05).
We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.
心脏同种异体移植血管病(CAV)限制了心脏移植(HTx)后的生存,其发病机制尚未完全阐明。我们旨在研究广泛的生物标志物及其与 HTx 患者的微血管和大血管 CAV 以及主要不良心脏事件的相关性。
我们使用新型蛋白质组学面板评估了 48 例 HTx 患者的 91 种心血管疾病相关蛋白。根据冠状动脉造影、光学相干断层扫描和 O-H O 正电子发射断层扫描成像确定的微血管和大血管 CAV 负担,将患者分为两组。主要不良心脏事件包括 CAV 进展、心力衰竭、治疗性排斥反应和心血管死亡。
我们发现两种参与胆固醇稳态的蛋白质存在一致差异:前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9(PCSK9)显著增加(p<0.05),对氧磷酶 3(PON3)显著降低(p<0.05)。微血管 CAV 患者的 N 端脑钠肽前体(NT-proBNP)显著升高(p<0.05),发生主要不良心脏事件的患者和大血管 CAV 患者的 NT-proBNP 略有升高(p=0.10 和 p=0.05)。
我们发现两种参与胆固醇稳态的蛋白质发生了一致变化,这两种蛋白可能是 CAV 发病机制中的重要参与者:PON3 和 PCSK9。NT-proBNP 在所有组中也显示出一致的变化,但仅在微血管 CAV 患者中达到统计学意义。我们的结果需要在未来的研究中进一步验证。