Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

作者全名："Li, Yan; Chen, Yunwei; Yang, Lingzhi; Bai, Jingwen; Feng, Panpan; Tang, Ping; Xiang, Rui; Huang, Wei; Li, Ailing"

作者地址："[Li, Yan; Chen, Yunwei; Yang, Lingzhi; Bai, Jingwen; Feng, Panpan; Tang, Ping; Xiang, Rui; Huang, Wei; Li, Ailing] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Cardiovasc Lab, Chongqing, Peoples R China; [Li, Yan; Chen, Yunwei; Yang, Lingzhi; Bai, Jingwen; Huang, Wei; Li, Ailing] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Li, Ailing] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Li, AL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：PULMONARY CIRCULATION

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001026901800001

JCR分区：Q2

影响因子：2.2

年份：2023

卷号：13

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：ADAMTSL4; correlation; CTEPH; IPAH; levels

摘要："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, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 & PLUSMN; 0.73 ng/mL, p < 0.01) and CTEPH (4.22 & PLUSMN; 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 & PLUSMN; 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) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP."

基金机构："First Affiliated Hospital of Chongqing Medical University [HLJJ2020-01]; National Natural Science Foundation of China [82270061]; National Key Research and Development Program of China [2022YFC2703902]; Chongqing National Natural Science Foundation [cstc2021jcyj-msxmX0474]; Chongqing Municipal Health and Health Commission; Chongqing science and Technology Bureau [2020FYYX075, 2020FYYX225]"

基金资助正文："First Affiliated Hospital of Chongqing Medical University, Grant/Award Number: HLJJ2020-01; National Natural Science Foundation of China, Grant/Award Number: 82270061; National Key Research and Development Program of China, Grant/Award Number: 2022YFC2703902; Chongqing National Natural Science Foundation, Grant/Award Number: cstc2021jcyj-msxmX0474; Chongqing Municipal Health and Health Commission and Chongqing science and Technology Bureau, Grant/Award Numbers: 2020FYYX075, 2020FYYX225"