From the Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Arterioscler Thromb Vasc Biol. 2014 Feb;34(2):270-8. doi: 10.1161/ATVBAHA.113.302610. Epub 2013 Dec 5.
The response-to-tissue-injury theory is currently the favorite paradigm to investigate valve pathology. To the best of our knowledge, there are currently no in vivo valve injury models. There are few calcific aortic valve stenosis (AVS) models that develop hemodynamically significant stenosis. Here, we investigated the effect of direct mechanical injury on aortic valves in vivo and developed a novel mouse model of calcific AVS.
Aortic valve injury was created by inserting and moving a spring guidewire under echocardiographic guidance into the left ventricle of male C57/BL6 mice via right common carotid artery. Serial echocardiographic measurements revealed that aortic velocity was increased 1 week after injury and persistently increased until 16 weeks after injury. AVS mice showed a higher heart weight/body weight ratio and decreased left ventricular fractioning shortening 4 weeks after injury, compared with sham mice. We found remarkable proliferation of valve leaflets 4 weeks after injury. Proliferative valves showed increased production of reactive oxygen species and expression of inflammatory cytokines and osteochondrogenic factors. Alizarin red staining showed valvular calcification 12 weeks after injury.
We report a novel calcific AVS model to support the response-to-tissue-injury theory. This model may be a valuable tool for analyzing the mechanism of AVS and assessing therapeutic options.
目前，组织损伤反应理论是研究瓣膜病理学的首选范例。据我们所知，目前尚无体内瓣膜损伤模型。很少有发展为血流动力学显著狭窄的钙化性主动脉瓣狭窄（AVS）模型。在这里，我们研究了直接机械损伤对体内主动脉瓣的影响，并开发了一种新的钙化性 AVS 小鼠模型。
通过右颈总动脉将弹簧导丝在超声心动图引导下插入并在左心室中移动，从而造成主动脉瓣损伤。连续的超声心动图测量显示，损伤后 1 周主动脉速度增加，并持续增加至损伤后 16 周。与假手术组相比，AVS 小鼠在损伤后 4 周显示出更高的心脏重量/体重比和左心室缩短分数降低。我们发现损伤后 4 周瓣膜小叶有明显的增殖。增殖的瓣膜显示出增加的活性氧产生以及炎症细胞因子和骨软骨形成因子的表达。茜素红染色显示损伤后 12 周出现瓣膜钙化。
我们报告了一种新的钙化性 AVS 模型，以支持组织损伤反应理论。该模型可能是分析 AVS 机制和评估治疗选择的有价值工具。
