Clinical outcomes of bosentan in pulmonary arterial hypertension do not correlate with levels of TIMPs
Clinical outcomes of bosentan in pulmonary arterial hypertension do not correlate with levels of TIMPs
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DOI：
10.1111/j.1365-2362.2006.01686.x
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发表时间：
2006-09-01
影响因子：
5.5
通讯作者：
Antonaci, S.
中科院分区：
文献类型：
--
作者：
Giannelli, G.;Iannone, F.;Antonaci, S.
基质金属蛋白酶（MMP）及其抑制剂组织金属蛋白酶抑制剂（TIMP）参与组织炎症和纤维化过程。波生坦治疗已被证明可改善伴有或不伴有系统性硬化症（SSc）的肺动脉高压（PAH）患者的临床结果，并可调节血清基质金属蛋白酶-9的水平。我们测量了长期波生坦治疗伴有和不伴有PAH的SSc患者与健康供者（HD）的血清中TIMP- 1和TIMP-2的含量。材料与方法采用酶联免疫吸附法（elisa）检测HD （n = 16）和SSc （n = 35）患者血清中总timp -1和timp -2的含量，其中SSc合并PAH （n = 23）和PAH合并患者（n = 12）。结果SSc患者与HD患者相比，TIMP-1和TIMP-2的平均水平均显著升高，但SSc合并PAH和不合并PAH的患者之间无差异。在8例波生坦治疗的患者中，TIMP-1和TIMP-2水平在1年治疗期间没有变化，而波生坦在1年后使6分钟步行距离增加了136米，以及临床结果。结论与HD相比，SSc患者的TIMP-1和TIMP-2水平升高，表明抑制蛋白水解使ECM蛋白积累。由于波生坦不刺激timp，它似乎有利于蛋白水解失衡，并增加ECM蛋白的周转。
Background Matrix metalloproteinases (MMP) and their *inhibitors, tissue inhibitors of metalloproteinases (TIMP), are involved in tissue inflammation and fibrotic processes. Treatment with bosentan has been shown to improve the clinical outcome of patients with pulmonary arterial hypertension (PAH) with and without association with systemic sclerosis (SSc), and also to modulate the serum levels of matrix metalloproteases-9. We measured TIMP- 1 and TIMP-2 in the serum of patients with SSc with and without PAH treated with long-term bosentan compared with healthy donors (HD).Materials and methods Serum samples from HD (n = 16) and patients with SSc (n = 35), including patients with SSc without PAH (n = 23) and patients with PAH (n = 12), were analyzed using enzyme-linked immunosorbent assays (ELISAs) for totalTIMP-1 andTIMP-2.Results Both mean TIMP-1 and TIMP-2 levels were significantly increased in patients with SSc compared with HD, but no differences were observed between patients with SSc with and without PAH. In the eight bosentan-treated patients, TIMP-1 and TIMP-2 levels did not change during 1 year of treatment, while bosentan increased the 6-min walking distance by 136 meters after 1 year, as well as clinical outcomes.Conclusions Increased levels of TIMP-1 and TIMP-2 in patients with SSc compared with HD suggest that the inhibition of proteolysis allows the accumulation of ECM proteins. As bosentan does not stimulate TIMPs, it appears to favour proteolytic imbalance and to increase the turnover of ECM proteins.