Preoperative serum LOXL2 levels are elevated in patients with pulmonary hypertension undergoing mitral valve surgery in a prospective observational cohort study.
Sineád M Nyhan, Mahin Gadkari, Travis Brady, Marta Martinez Yus, Rira Choi, Maria Bauer, Samira Vithani, Joseph Walpole, Allison G Hays, Hamza Aziz, Ahmet Kilic, Michael Robich, James S Gammie, Lakshmi Santhanam, Jochen Steppan
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引用次数: 0
Abstract
Lysyl oxidase-like 2 (LOXL2) is associated with vascular remodeling associated in pulmonary hypertension (PH). This study evaluates the potential of serum LOXL2 levels as a clinical biomarker. We enrolled 158 patients undergoing mitral valve surgery. Using echocardiographic right ventricular systolic pressures (RVSPs), patients were stratified into those with and without PH preoperative, postoperative, and postdischarge. Healthy volunteers served as a nonsurgical control. Serum LOXL2 concentrations preincision were compared with RVSPs using simple regression and their relationship to PH using one-way ANOVA with Tukey's posttest. Serum LOXL2 concentrations were significantly higher in patients with PH compared with patients without PH (2,718 ± 5,187 pg/mL vs. 640 ± 1,367 g/mL; P = 0.0009) and compared with healthy volunteers (283 ± 615 pg/mL; P = 0.04). There was a positive correlation between RVSPs and serum LOXL2 concentrations (P = 0.02, r2 = 0.08). Serum LOXL2 levels positively correlated with intraoperative indices of pulmonary compliance, suggesting that PH in this cohort may primarily represent postcapillary PH. Patients with PH postprocedure (and before discharge) had greater preprocedure serum LOXL2 levels compared with patients without PH (4,348 ± 8,498 pg/mL vs. 1,281 ± 2,329 pg/mL, P = 0.006), as did patients assessed after discharge (1,359 ± 2,693 pg/mL vs. 4,195 ± 6,568 pg/mL, P = 0.009). Patients with persistent PH or new PH had elevated presurgical LOXL2 levels compared with those without PH at both timepoints (4,301 ± 7,717 pg/mL vs. 556.6 ± 835.8 pg/mL, P = 0.02; 2,902 ± 5,255 pg/mL vs. 556.6 ± 835.8 pg/mL, P = 0.03). Serum LOXL2 is elevated in patients with PH. LOXL2 is a potential PH biomarker in patients undergoing mitral valve surgery. This could have implications for follow-up care.NEW & NOTEWORTHY Serum LOXL2 levels are elevated in patients with PH undergoing mitral valve surgery, and they do correlate with disease severity and persistence, suggesting that LOXL2 plays a role in human PH and holds potential as an important biomarker for PH.
目的:赖氨酸氧化酶样-2 (LOXL2)与肺动脉高压(PH)相关的血管重构相关。本研究评估了血清LOXL2水平作为临床生物标志物的潜力。方法:158例接受二尖瓣手术的患者。通过超声心动图右心室收缩压(RVSPs),将患者分为术前、术后和出院后有无PH的患者。健康志愿者作为非51手术对照。采用简单回归法比较切口前血清LOXL2浓度与RVSPs,并采用单因素方差分析与Tukey-posttest比较其与PH的关系。结果:PH患者血清LOXL2浓度明显高于无PH患者(2,718±5187pg/ml vs. 640±1367 g/ml;P=0.0009),与健康志愿者相比(283±615pg/ml;P = 0.04)。RVSPs与血清LOXL2浓度呈正相关(p=0.02, r2=0.08)。血清LOXL2水平与术中肺顺应性指标呈正相关,表明该队列中的PH可能主要代表毛细血管后PH。术后(和出院前)有PH的患者术前血清LOXL2水平高于无PH的患者(4348±8498pg/ml vs 1281±2329pg/ml, P=0.006);出院后评估的患者也是如此(1359±2693pg/ml vs. 4195±6568pg/ml, P=0.009)。在两个时间点,持续性PH或新发PH患者术前LOXL2水平均高于无PH患者(4301±7717pg/ml vs 556.6±835.8pg/ml, P= 0.02;2902±5255pg/ml vs 556.6±835.8pg/ml, P=0.03)。结论:PH患者血清LOXL2升高,LOXL2是二尖瓣手术患者潜在的PH生物标志物。这可能会对后续护理产生影响。
期刊介绍:
The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.