The Department of Surgery, San Francisco Department of Veterans Affairs Medical Center/University of California San Francisco and Northern California Institute for Research and Education, San Francisco, CA 94121, USA.
Int J Exp Pathol. 2011 Feb;92(1):50-6. doi: 10.1111/j.1365-2613.2010.00744.x. Epub 2010 Oct 29.
Coronary artery ectasia (CAE) is generally diagnosed in patients undergoing arteriography for presumptive atherosclerotic coronary artery disease. CAE is commonly considered as a variant of atherosclerotic disease; however, recent studies suggest that CAE is the result of a systemic vascular disorder. There is increasing evidence that aneurysmal vascular disease is a systemic disorder characterized by enhanced expression of pro-inflammatory cytokines and increased synthesis of enzymes capable of degrading elastin and other components of the vascular wall. Matrix metalloproteinase-2 degrades a number of extracellular substrates, including elastin and has been shown to play a critical role in the development of abdominal aortic aneurysms. This study characterizes the development of CAE in a unique murine transgenic model with cardiac-specific expression of active MMP-2. Transgenic mice were engineered to express an active form of MMP-2 under control of the α-myosin heavy chain promoter. Coronary artery diameters were quantified, along with studies of arterial structure, elastin integrity and vascular expression of the MMP-2 transgene. Latex casts quantified total coronary artery volumes and arterial branching. Mid-ventricular coronary luminal areas were increased in the MMP-2 transgenics, coupled with foci of aneurysmal dilation, ectasia and perivascular fibrosis. There was no evidence for atherogenesis. Coronary vascular elastin integrity was compromised and coupled with inflammatory cell infiltration. Latex casts of the coronary arteries displayed ectasia with fusiform dilatation. The MMP-2 transgenic closely replicates human CAE and supports a critical and initiating role for this enzyme in the pathogenesis of this disorder.
冠状动脉扩张症（CAE）通常在因疑似动脉粥样硬化性冠状动脉疾病而行血管造影的患者中诊断。CAE 通常被认为是动脉粥样硬化疾病的一种变体；然而，最近的研究表明 CAE 是全身性血管疾病的结果。越来越多的证据表明，动脉瘤性血管疾病是一种全身性疾病，其特征是促炎细胞因子表达增强，以及能够降解弹性蛋白和血管壁其他成分的酶的合成增加。基质金属蛋白酶-2 降解许多细胞外基质底物，包括弹性蛋白，并已被证明在腹主动脉瘤的发展中起关键作用。本研究在一种具有心脏特异性表达活性 MMP-2 的独特的小鼠转基因模型中描述了 CAE 的发展。通过控制α肌球蛋白重链启动子，将 MMP-2 的活性形式工程化表达在转基因小鼠中。定量了冠状动脉直径，并进行了动脉结构、弹性蛋白完整性和 MMP-2 转基因的血管表达研究。乳胶铸型定量了总冠状动脉体积和动脉分支。MMP-2 转基因小鼠的中层心室冠状动脉腔面积增加，伴有动脉瘤样扩张、扩张和血管周围纤维化的焦点。没有动脉粥样硬化形成的证据。冠状动脉血管弹性蛋白完整性受损，并伴有炎症细胞浸润。冠状动脉乳胶铸型显示出扩张样扩张伴梭形扩张。MMP-2 转基因小鼠非常类似于人类 CAE，并支持这种酶在这种疾病发病机制中的关键和起始作用。
