Martinez-Aguilar Esther, Gomez-Rodriguez Violeta, Orbe Josune, Rodriguez Jose A, Fernández-Alonso Leopoldo, Roncal Carmen, Páramo Jose A
Department of Vascular Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain.
Laboratory of Atherothrombosis, Division of Cardiovascular Sciences, CIMA, University of Navarra, Pamplona, Spain.
J Vasc Surg. 2015 Feb;61(2):428-35. doi: 10.1016/j.jvs.2014.09.002. Epub 2014 Oct 23.
Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years.
MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls.
PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03).
Our results suggest that MMP-10 is associated with severity and poor outcome in PAD.
外周动脉疾病（PAD）在心血管（CV）发病率和死亡率方面预后较差。基质金属蛋白酶（MMPs）通过降解细胞外基质成分促进血管重塑，并在动脉粥样硬化中发挥作用，如MMP-10（基质溶解素-2）所示。本研究根据疾病严重程度和CV危险因素分析了PAD患者的MMP-10水平，并在随访2年后评估了MMP-10对下肢动脉疾病CV事件和死亡率的预后价值。
采用酶联免疫吸附测定法测量了187例PAD患者和200例性别匹配对照者的MMP-10。
与对照组相比，PAD患者的MMP-10水平升高（对照组为702±326 pg/mL，PAD患者为946±473 pg/mL；P<.001），基质金属蛋白酶组织抑制剂1水平降低（对照组为312±117 ng/mL，PAD患者为235±110 ng/mL；P<.001）。在PAD患者中，与间歇性跛行患者（n = 99）相比，严重肢体缺血患者（n = 88）的MMP-10水平更高（1086±478 pg/mL对822±436 pg/mL；P<.001），而MMP-10/基质金属蛋白酶组织抑制剂1比值保持相似。单因素分析显示，PAD患者的MMP-10、年龄（P =.015）、高血压（P =.021）和踝臂指数（P =.006）之间存在关联，在调整其他CV危险因素后，这些因素仍与PAD严重程度显著相关。MMP-10三分位数最高的患者全因死亡率和CV死亡率的发生率增加（P<.03）。
我们的结果表明，MMP-10与PAD的严重程度和不良预后相关。
