Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
Matrix metalloproteinase 7 in diagnosis and differentiation of pulmonary arterial hypertension
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DOI：
10.1177/2045894019895414
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发表时间：
2019-10-01
影响因子：
2.6
通讯作者：
Radegran, Goran
中科院分区：
文献类型：
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作者：
Arvidsson, Mattias;Ahmed, Abdulla;Radegran, Goran
肺动脉高压是一种严重的疾病，其诊断往往被延误。基质金属蛋白酶被认为在血管重塑和肺动脉高压的发生发展中起作用。因此，我们的目的是研究基质金属蛋白酶作为生物标志物在诊断和鉴别与呼吸困难和肺动脉高压的各种原因相关的肺动脉高压中的潜在作用。采用邻近延伸分析方法，对20例正常人、48例肺动脉高压、20例慢性血栓栓塞性肺动脉高压、33例心力衰竭射血分数保留或36例射血分数降低、15例心力衰竭射血分数降低和心力衰竭射血分数保留而不伴有肺动脉高压的患者的静脉血浆中10种基质金属蛋白酶及其相关蛋白进行了分析。与对照组相比，肺动脉高压患者血浆基质金属蛋白酶-2、-7、-9、-12和TIMP-4水平升高(P<0.01)。此外，肺动脉高压患者血浆基质金属蛋白酶-7水平低于所有其他疾病组(p<；0.0081)，但高于对照组(p<；0.0001)。基质金属蛋白酶-7的受试者工作特性分析显示，在其他疾病组中，检测肺动脉高压的敏感性为58.7%，特异性为83.3%。血浆基质金属蛋白酶-7可能提供一种潜在的新的诊断工具，以鉴别肺动脉高压与其他原因的呼吸困难，包括心力衰竭伴或不伴肺高压和健康对照。基质金属蛋白酶-7可能进一步参与了肺动脉高压和肺动脉高压的发生发展。未来的研究将探讨基质金属蛋白酶-7在肺动脉高压的鉴别诊断和早期诊断中的临床应用价值，以及它与肺动脉高压发病机制的关系。
Pulmonary arterial hypertension is a severe disease for which diagnosis often is delayed. Matrix metalloproteinases have been suggested to play a role in vascular remodeling and pulmonary hypertension development. Our aim was therefore to investigate the potential role of matrix metalloproteinases as biomarkers in diagnosis and differentiation of pulmonary arterial hypertension in relation to various causes of dyspnea and pulmonary hypertension. Using proximity extension assays, 10 matrix metalloproteinases and associated proteins were analyzed in venous plasma from healthy controls (n = 20), as well as patients diagnosed with pulmonary arterial hypertension (n = 48), chronic thromboembolic pulmonary hypertension (n = 20), pulmonary hypertension due to heart failure with preserved (n = 33) or reduced (n = 36) ejection fraction, and heart failure with reduced ejection fraction and heart failure with preserved ejection fraction without pulmonary hypertension (n = 15). Plasma levels of matrix metalloproteinase-2, -7, -9, -12 and TIMP-4 were elevated (p < 0.01) in pulmonary arterial hypertension compared to controls. Plasma levels of matrix metalloproteinase-7 were furthermore lower (p < 0.0081) in pulmonary arterial hypertension than in all the other disease groups, but higher compared to controls (p < 0.0001). Receiver operating characteristic analysis of matrix metalloproteinase-7 resulted in sensitivity of 58.7% and a specificity of 83.3% for detecting pulmonary arterial hypertension among the other disease groups. Plasma matrix metalloproteinase-7 may provide a potential new diagnostic tool to differentiate pulmonary arterial hypertension from other causes of dyspnea, including heart failure with or without pulmonary hypertension and healthy controls. Matrix metalloproteinase-7 may furthermore be involved in the development of pulmonary hypertension and pulmonary arterial hypertension. Future studies investigating the clinical usefulness of matrix metalloproteinase-7 in the differentiation and earlier diagnosis of pulmonary arterial hypertension, as well as its relationship to pulmonary arterial hypertension pathogenesis, are encouraged.