Clinic of Internal Medicine II, University of Ulm, Ulm, Germany.
Biomarkers. 2010 Sep;15(6):523-32. doi: 10.3109/1354750X.2010.492431.
Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role.
We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed.
In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy.
Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.
除了持续存在的肺动脉高压和增加的肺血管阻力外，肺组织重塑以及随后的右心是肺动脉高压（PH）的关键病理机制。在这种情况下，细胞外基质的维持起着核心作用。
我们检验了这样一个假设，即血浆基质金属蛋白酶（MMP）-2、基质金属蛋白酶抑制剂（TIMP）-4 和 tenascin C（TNC）的浓度可用作评估 PH 严重程度的生物标志物。因此，我们比较了 36 名 PH 患者和 44 名年龄和性别匹配的健康志愿者的 MMP-2、TIMP-4、TNC 和 N 末端 B 型利钠肽（NT-proBNP）的浓度。此外，还评估了肺功能、6 分钟步行距离和右心功能。
在 PH 患者中，检测到 MMP-2、TIMP-4、TNC 和 NT-proBNP 的血浆水平显著升高。特别是，TIMP-4 在 NYHA 分级较高的患者和严重右心室肥厚的患者中显著增加。
监测 PH 患者的血浆 TIMP-4 以及在较小程度上监测 MMP-2 和 TNC 水平，可能有助于评估 PH 药物治疗对组织重塑的有益效果。
