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心脏移植受者中与 91 种心血管生物标志物相关的微血管和大血管心脏移植物血管病:一项探索性研究。

Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients-An exploratory study.

机构信息

Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.

出版信息

Clin Transplant. 2021 Jan;35(1):e14133. doi: 10.1111/ctr.14133. Epub 2020 Nov 20.

DOI:10.1111/ctr.14133
PMID:33128247
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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)。

结论

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。

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