Arvidsson Mattias, Ahmed Abdulla, Säleby Joanna, Hesselstrand Roger, Rådegran Göran
Department of Clinical Sciences Lund, Cardiology, Faculty of Medicine Lund University Lund Sweden.
The Hemodynamic Lab, The Section for Heart Failure and Valvular Disease, VO Heart and Lung Medicine Skåne University Hospital Lund Sweden.
Pulm Circ. 2022 Feb 4;12(1):e12041. doi: 10.1002/pul2.12041. eCollection 2022 Jan.
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and remodeling of the pulmonary vessels. Risk stratification in PAH could potentially be improved by including novel biomarkers related to PAH pathobiology. We aimed to investigate the relationship between extracellular matrix (ECM)-related proteins, survival, and European Society of Cardiology and European Respiratory Society (ESC/ERS) risk stratification scores in patients with PAH. Plasma samples and hemodynamics were collected from PAH patients during right heart catheterizations at diagnosis ( = 48) and early follow-up, after treatment initiation ( = 33). Plasma levels of 14 ECM-related proteins, with altered levels in PAH compared to healthy controls, were analyzed with proximity extension assays, and related to hemodynamics, transplant-free survival time, and ESC/ERS risk score. Glypican-1 levels were higher before versus after treatment initiation ( = 0.048). PAH patients with high plasma levels of matrix metalloproteinase (MMP) -2, MMP-7, MMP-9, MMP-12, perlecan, and tissue inhibitor of metalloproteinase 4 (TIMP-4) at baseline, had worse transplant-free survival ( < 0.03) than patients with low levels. Hazard ratio (95% confidence interval) was for MMP-2 1.126 (1.011-1.255), perlecan 1.0099 (1.0004-1.0196), and TIMP-4 1.037 (1.003-1.071) in age and sex-adjusted Cox-regression model. MMP-2 correlated with ESC/ERS risk scores ( = 0.34, = 0.019), mean right atrial pressure ( = 0.44, = 0.002), NT-proBNP ( = 0.49, ≤ 0.001), and six-minute walking distance ( = -0.34, = 0.02). The present study indicates that high levels of MMP-2, perlecan, and TIMP-4 are associated with poor survival in PAH. High plasma MMP-2, correlated with poor prognosis in PAH. Further validation in larger studies is needed to better determine this association.
肺动脉高压（PAH）是一种危及生命的疾病，其特征为肺血管收缩和重塑。纳入与PAH病理生物学相关的新型生物标志物可能会改善PAH的风险分层。我们旨在研究PAH患者细胞外基质（ECM）相关蛋白、生存率与欧洲心脏病学会和欧洲呼吸学会（ESC/ERS）风险分层评分之间的关系。在诊断时（n = 48）和治疗开始后的早期随访（n = 33）进行右心导管检查期间，收集PAH患者的血浆样本和血流动力学数据。使用邻位延伸分析检测14种与ECM相关的蛋白的血浆水平，这些蛋白在PAH患者中的水平与健康对照相比有所改变，并将其与血流动力学、无移植生存时间和ESC/ERS风险评分相关联。治疗开始前与开始后相比，磷脂酰肌醇蛋白聚糖-1水平更高（P = 0.048）。基线时血浆基质金属蛋白酶（MMP）-2、MMP-7、MMP-9、MMP-12、基底膜聚糖和金属蛋白酶组织抑制剂4（TIMP-4）水平高的PAH患者，其无移植生存率比水平低的患者更差（P < 0.03）。在年龄和性别校正的Cox回归模型中，MMP-2的风险比（95%置信区间）为1.126（1.011 - 1.255），基底膜聚糖为1.0099（1.0004 - 1.0196），TIMP-4为1.037（1.003 - 1.071）。MMP-2与ESC/ERS风险评分相关（r = 0.34，P = 0.019）、平均右心房压相关（r = 0.44，P = 0.002）、N末端脑钠肽前体相关（r = 0.49，P ≤ 0.001）以及与六分钟步行距离相关（r = -0.34，P = 0.02）。本研究表明，MMP-2、基底膜聚糖和TIMP-4的高水平与PAH患者的不良生存相关。血浆MMP-2水平高与PAH患者的不良预后相关。需要在更大规模的研究中进一步验证以更好地确定这种关联。
