TIMP-1: A Circulating Biomarker for Pulmonary Hypertension Diagnosis Among Chronic Obstructive Pulmonary Disease Patients.
TIMP-1: A Circulating Biomarker for Pulmonary Hypertension Diagnosis Among Chronic Obstructive Pulmonary Disease Patients.
复制标题
DOI：
10.3389/fmed.2021.774623
复制
发表时间：
2021
影响因子：
3.9
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
He W;Liu C;Liao J;Liu F;Lei H;Wei D;Ruan H;Kunwar B;Lu W;Wang J;Wang T
肺动脉高压（PH）是慢性阻塞性肺疾病（COPD）的常见并发症，导致COPD患者死亡率增加。然而，没有血液生物标志物来识别COPD中的PH。在这里，我们研究了循环血管生成因子和细胞因子是否可以作为COPD-PH患者的生物标志物。应用血管生成和细胞因子蛋白质组芯片技术，分别检测了4例COPD合并PH（COPD-PH）和4例COPD不伴PH（COPD）患者血浆中36种细胞因子和55种血管生成相关蛋白的水平，其中组织金属蛋白酶抑制因子1（TIMP-1）和血小板反应蛋白1（TSP-1）在两组间差异有统计学意义。采用酶联免疫吸附试验（ELISA）测定验证队列（COPD-PH，n = 28; COPD，n = 18）中的TIMP-1和TSP-1，TIMP-1是COPD-PH与COPD患者之间唯一有显著差异的因素（P < 0.01）。Logistic回归分析显示TIMP-1升高是COPD合并PH的独立危险因素[OR = 1.258，95% CI：1.005-1.574，P < 0.05]。接下来，我们探讨了TIMP-1在暴露于香烟烟雾提取物（CSE，COPD的主要病因）的人肺动脉平滑肌细胞（hPASMCs）中的表达水平和功能。在培养的hPASMCs中，CSE处理增加TIMP-1蛋白水平和细胞增殖，并且外源性TIMP-1（25 ng/mL）处理抑制CSE诱导的hPASMCs增殖。总之，我们的研究结果表明，TIMP-1升高可以作为诊断COPD患者PH的循环生物标志物，并且TIMP-1升高在COPD-PH中可以是适应性的。
Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) and induces increased mortality among COPD patients. However, there are no blood biomarkers to identify PH in COPD. Here, we investigated whether circulating angiogenic factors and cytokines could serve as (a) biomarker (s) for COPD-PH patients. Using Angiogenesis and Cytokine proteome profile array assay, we measured the level of 36 cytokines and 55 angiogenesis-associated proteins in plasma from four COPD patients with PH (COPD-PH) and four COPD patients without PH (COPD), respectively, tissue inhibitor of metalloproteinase 1 (TIMP-1) and thrombospondin 1(TSP-1) were significantly different between the two groups. Enzyme-linked immunosorbent assay (ELISA) was applied to measured TIMP-1 and TSP-1 in a validation cohort (COPD-PH, n = 28; COPD, n = 18), and TIMP-1 was the only factor that was significantly different between COPD-PH and COPD patients (P < 0.01). Logistic regression analysis demonstrated that elevated TIMP-1 was an independent risk factor for COPD-PH [odds ratio (OR) = 1.258, 95% CI: 1.005–1.574, P < 0.05). Next, we explored the expression level and function of TIMP-1 in human pulmonary arterial smooth muscle cells (hPASMCs) exposed to cigarette smoking extract (CSE, a major etiological factor of COPD). In cultured hPASMCs, CSE treatment increased both TIMP-1 protein level and cell proliferation, and exogenous TIMP-1 (25 ng/mL) treatment inhibited CSE-induced hPASMCs proliferation. Overall, our results indicated that TIMP-1 elevation could serve as a circulating biomarker to diagnose PH among COPD patients, and TIMP-1 elevation in COPD-PH could be adaptive.
登录
查看更多内容
DOI：
10.1016/s0140-6736(18)32203-7
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2017 Causes of Death Collaborators
通讯作者：
GBD 2017 Causes of Death Collaborators
DOI：
10.1161/atvbaha.120.314152
发表时间：
2020-09-01
影响因子：
8.7
作者：
Khandagale, Avinash;Aberg, Mikael;Christersson, Christina
通讯作者：
Christersson, Christina
MMP-2和MMP-9有助于肺内皮细胞缺氧/15-HETE产生的血管生成作用
影响因子：
5
作者：
Liu, Ying;Zhang, Hongyue;Zhu, Daling
通讯作者：
Zhu, Daling
影响因子：
6.4
作者：
Knight, Daniel S.;Kotecha, Tushar;Coghlan, J. Gerry
通讯作者：
Coghlan, J. Gerry
影响因子：
3.8
作者：
Nam, Joon Yeul;Choe, A. Reum;Yoo, Kwon
通讯作者：
Yoo, Kwon