基质金属蛋白酶活性在急性心肌梗死中的临床意义

Clinical significance of matrix metalloproteinases activity in acute myocardial infarction.

作者信息

Papadopoulos D P, Moyssakis I, Makris T K, Poulakou M, Stavroulakis G, Perrea D, Votteas V E

机构信息

Department of Cardiology, Laiko Hospital of Athens, 6-8 Glykonos street, 106-75 Athens, Greece.

出版信息

Eur Cytokine Netw. 2005 Jun;16(2):152-60.

PMID:15941687

Abstract

Matrix metalloproteinases (MMP) degrade myocardial fibrillar collagen in acute myocardial infarction (MI) patients. Their activity is tightly controlled in normal myocardium by a family of closely related tissue inhibitors known as TIMP. An imbalance in their activity might contribute to post-MI remodeling. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured, using relevant ELISA kits, in 24 (22 males-2 females), acute MI patients with a mean age 59 +/- 14 years. Blood samples were taken on admission (0 h), and 3 h, 6 h, 9 h, 18 h, 24 h, 36 h, 48 h, 3rd, 4th, 5th, 7th, 15th, 30th days after MI. All patients underwent coronary arteriography with ventriculography for estimation of left ventricular ejection fraction (LVEF) and extent of coronary artery diseases, and echocardiographic study for measuring end-diastolic diameter (EDD). Ten patients with an LVEF < 45%, an EDD > 47.5 mm, and heart failure symptoms were included in group A and compared against 12 patients with an LVEF > 45% an EDD < 47.5 mm in group B. Mean plasma concentrations of MMP-1 were higher by 21% in group A (1.3 +/- 0.2 ng/mL) compared to group B (1 +/- 0.1 ng/mL) over the total study period. TIMP-1 plasma concentrations showed very little difference between the 2 groups, (704 +/- 213 ng/mL versus 691 +/- 165 ng/mL, (6%)). Finally, plasma concentrations of MMP-1/TIMP-1 complex were lower by -36% in group A with a mean value of 2.7 +/- 0.6 ng/mL versus 3.7 +/- 0.5 ng/mL in group B. Mean values for the differences were significant at time points 0, 6, 18, 24 and 48 hours for MMP-1 (p < 0.036), and on 48 h and the 4th day for MMP-1/TIMP-1 complex (p < 0.031). Moreover, a good correlation was found between plasma concentrations of creatine kinase (CK) and MMP-1 at 18 h (r = 0.422, p = 0.041) and on the 4th day (r = 0.67, p = 0.046), and TIMP-1 on the 4th day (r = 0.67, p = 0.047). Additionally, mean values for LVEF were 35.8 +/- 8.8% in group A versus 51.2 +/- 1.8% (p = 0.00014) in group B. Also, the EDD in-group A was 52.1 +/- 6.9 mm versus 42.9 +/- 3.2 mm in group B (p = 0.00013). In acute MI patients, increased MMP-1, with no change in TIMP-1, is associated with left ventricular dysfunction and dilatation, suggesting that increased collagenolytic activity contributes to loss of LV function.

摘要

基质金属蛋白酶（MMP）可降解急性心肌梗死（MI）患者的心肌纤维状胶原。在正常心肌中，它们的活性受到一类名为组织金属蛋白酶抑制剂（TIMP）的密切相关组织抑制剂家族的严格控制。它们活性的失衡可能导致心肌梗死后的重塑。使用相关酶联免疫吸附测定试剂盒，对24例（22例男性 - 2例女性）平均年龄为59±14岁的急性心肌梗死患者的血浆MMP - 1、TIMP - 1和MMP - 1/TIMP - 1复合物水平进行了测量。在入院时（0小时）以及心肌梗死后3小时、6小时、9小时、18小时、24小时、36小时、48小时、第3天、第4天、第5天、第7天、第15天、第30天采集血样。所有患者均接受了冠状动脉造影及心室造影以评估左心室射血分数（LVEF）和冠状动脉疾病的程度，并进行了超声心动图检查以测量舒张末期直径（EDD）。将10例LVEF < 45%、EDD > 47.5 mm且有心力衰竭症状的患者纳入A组，并与12例LVEF > 45%、EDD < 47.5 mm的B组患者进行比较。在整个研究期间，A组MMP - 1的平均血浆浓度（1.3±0.2 ng/mL）比B组（1±0.1 ng/mL）高21%。两组间TIMP - 1血浆浓度差异很小，（704±213 ng/mL对比如691±165 ng/mL，（6%））。最后，A组MMP - 1/TIMP - 1复合物的血浆浓度比B组低 - 36%，平均值分别为2.7±0.6 ng/mL和3.7±0.5 ng/mL。MMP - 1在时间点0、6、18、24和48小时差异的平均值具有统计学意义（p < 0.036），MMP - 1/TIMP - 1复合物在48小时和第4天差异的平均值具有统计学意义（p < 0.031）。此外，在18小时（r = 0.422，p = 0.041）和第4天（r = 0.67，p = 0.046）时，肌酸激酶（CK）与MMP - 1的血浆浓度之间以及在第4天（r = 0.67，p = 0.047）时CK与TIMP - 1的血浆浓度之间发现了良好的相关性。另外，A组LVEF的平均值为35.8±8.8%，而B组为51.2±1.8%（p = 0.00014）。而且，A组的EDD为52.1±6.9 mm对比B组为42.9±3.2 mm（p = 0.00013）。在急性心肌梗死患者中，MMP - 1升高而TIMP - 1无变化与左心室功能障碍和扩张相关，提示胶原olytic活性增加导致左心室功能丧失。