Li Yan, Chen Yunwei, Yang Lingzhi, Li Yan, Bai Jingwen, Feng Panpan, Tang Ping, Xiang Rui, Huang Wei, Li Ailing
Cardiovascular Laboratory, Department of Cardiology The First Affiliated Hospital of Chongqing Medical University Chongqing China.
Institute of Life Science Chongqing Medical University Chongqing China.
Pulm Circ. 2023 Jul 12;13(3):e12267. doi: 10.1002/pul2.12267. eCollection 2023 Jul.
Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup ( < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) ( = 0.305, < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.
特发性肺动脉高压（IPAH）和慢性血栓栓塞性肺动脉高压（CTEPH）可导致右心衰竭。我们旨在评估含血小板反应蛋白基序的解聚素和金属蛋白酶4（ADAMTSL4）的血浆蛋白水平及其与IPAH和CTEPH的关系。采用蛋白质组学分析测定8例IPAH患者和9名健康对照者的血浆ADAMTSL4蛋白水平。使用生物信息学工具评估肺组织中ADAMTSL4水平。通过蛋白质印迹法检测血小板衍生生长因子（PDGF）-BB处理的原代大鼠肺动脉平滑肌细胞（PASMCs）中ADAMTSL4的蛋白表达。采用酶联免疫吸附测定（ELISA）法检测45例患者（15例IPAH患者和30例CTEPH患者）的血浆ADAMTSL4浓度。评估ADAMTSL4水平与临床参数之间的相关性。在IPAH患者中，血浆ADAMTSL4蛋白水平显著高于健康对照者（倍数变化[FC] 1.85，<0.05），且mRNA表达水平显著升高（对数FC 0.66，<0.05）。与对照组相比，PDGF-BB处理的PASMCs中ADAMTSL4的蛋白表达显著增加（<0.05）。IPAH患者（4.71±0.73 ng/mL，<0.01）和CTEPH患者（4.22±0.66 ng/mL，<0.01）的血浆ADAMTSL4蛋白水平高于健康对照者（3.01±0.46 ng/mL）。根据受试者工作特征曲线，血浆ADAMATL4蛋白水平的截断值为3.55 ng/mL，且与平均肺动脉压（mPAP）呈正相关（=0.305，<0.05）。在IPAH和CTEPH患者中，血浆ADAMTSL4水平升高与mPAP呈正相关。
