Role of Osteoclastogenesis in Calcific Aortic Valve Disease

描述（由申请方提供）：炎症、纤维化和异位钙化是钙化性主动脉瓣疾病（CAVD）中观察到的常见病理。异位钙化对血管系统的机械功能特别有害，是CAVD患者瓣膜失效以及生物瓣膜失效的主要原因。在CAVD中，钙化的主要治疗方法是瓣膜置换术，这与相当高的发病率和死亡率以及显著的再植入率相关。目前没有药物 我们的初步数据表明，单核细胞衍生的炎性细胞具有调节体内异位钙化的潜力，类似于调节和再吸收骨中矿物质的单核细胞衍生的破骨细胞。我们的总体假设是，钙化在CAVD中积累，部分原因是关键炎症细胞功能和介质的缺失和/或缺乏，例如在破骨细胞中发现的那些旨在抑制和/或消退矿物质的细胞。通过工程细胞增强这些功能，我们可以预防甚至消除不必要的钙化。 (End摘要）

DESCRIPTION (provided by applicant): Inflammation, fibrosis and ectopic calcification are common pathologies observed in calcific aortic valve disease (CAVD). Ectopic calcification is particularly detrimental to the mechanical functions of the vasculature, and is the major cause of valve failure in patients with CAVD, as well as bioprosthetic valves. In CAVD, the major treatment for calcification is valve replacement therapy, which is associated with considerable morbidity and mortality, as well as a significant re- implantation rate. There is currently no drug or cell therapeutics that specifically target prevention and/or regression of calcification in CAVD Our preliminary data suggest that monocyte-derived inflammatory cells have the potential to regulate ectopic calcification in vivo similar to monocyte-derived osteoclasts that regulate and resorb mineral in bone. Our overall hypothesis is that calcifications accumulate in CAVD, in part, due to the absence and/or deficiency of key inflammatory cell functions and mediators, such as those found in osteoclasts that are designed to inhibit and/or regress mineral. By engineering cells to enhance these functions, we may prevent and even remove unwanted calcifications. (End of Abstract)