Finkelstein Ariel, Michowitz Yoav, Abashidze Anastasia, Miller Hylton, Keren Gad, George Jacob
The Department of Cardiology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, Israel.
Atherosclerosis. 2005 Apr;179(2):353-9. doi: 10.1016/j.atherosclerosis.2004.10.020. Epub 2004 Dec 22.
The prevalence of coronary ectasia (CE) appears to rise in recent years. However, the pathogenetic mechanisms that underlie this entity are not understood. We hypothesized that dysregulation of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) contributes to ectasia formation. We also evaluated the association of MMP with inflammatory or the neurohormonal markers.
We screened coronary angiographic procedures conducted in our hospital. Thirty-four patients with CEs were identified; 17 with a single ectasia and 17 with generalized ectasias. Two control groups; patients with atherosclerotic coronary disease (n=26) and patients with normal coronary arteries (n=27) were chosen randomly. Serum levels of MMP-2, MMP-3 and TIMP-1 were determined by ELISA. Pro B-type natriuretic peptide (proBNP) and high sensitivity C-reactive protein (hsCRP) serum levels were also measured.
Serum levels of MMP-2, MMP-3, TIMP-1, proBNP and hsCRP did not differ between the three groups of patients. However, subgroup analysis demonstrated that MMP-3 level is significantly lower in patients with generalized CEs compared to those with single vessel ectasia. We also found a statistically significant correlation between proBNP and MMP-2/TIMP-1 (for MMP-2: r(2)=0.3, p=0.003 and for TIMP-1 r(2)=0.42, p<0.000l). By performing subgroup analysis we found that this correlation is only demonstrated in patients with CEs. No correlation was demonstrated between hsCRP and MMPs/TIMP.
These observations suggest that MMP/TIMP imbalance is present in patients with generalized CE and may contribute to ectasia formation. This imbalance could be mediated by BNP.
近年来,冠状动脉扩张(CE)的患病率似乎有所上升。然而,导致这一病症的发病机制尚不清楚。我们推测循环基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)的失调促成了扩张的形成。我们还评估了MMP与炎症或神经激素标志物之间的关联。
我们筛查了在我院进行的冠状动脉造影检查。确定了34例CE患者;17例为单发扩张,17例为广泛性扩张。随机选择两个对照组;患有动脉粥样硬化性冠状动脉疾病的患者(n = 26)和冠状动脉正常的患者(n = 27)。通过酶联免疫吸附测定法测定血清MMP - 2、MMP - 3和TIMP - 1水平。还测量了B型利钠肽原(proBNP)和高敏C反应蛋白(hsCRP)血清水平。
三组患者的血清MMP - 2、MMP - 3、TIMP - 1、proBNP和hsCRP水平无差异。然而,亚组分析表明,与单发血管扩张患者相比,广泛性CE患者的MMP - 3水平显著降低。我们还发现proBNP与MMP - 2/TIMP - 1之间存在统计学显著相关性(对于MMP - 2:r(2)=0.3,p = 0.003;对于TIMP - 1,r(2)=0.42,p<0.0001)。通过进行亚组分析,我们发现这种相关性仅在CE患者中表现出来。hsCRP与MMPs/TIMP之间未显示相关性。
这些观察结果表明,广泛性CE患者存在MMP/TIMP失衡,可能促成扩张的形成。这种失衡可能由BNP介导。