Calcific Aortic Valve Disease: Molecular Mechanisms and Therapeutic Approaches.
Calcific Aortic Valve Disease: Molecular Mechanisms and Therapeutic Approaches.
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DOI：
10.15420/ecr.2015.10.2.108
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Alotti N
中科院分区：
文献类型：
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作者：
Lerman DA;Prasad S;Alotti N
钙化发生在动脉粥样硬化血管病变和主动脉瓣。钙化性主动脉瓣疾病（CAVD）是一种缓慢进行性疾病，范围从轻度瓣膜增厚（无血流阻塞，称为主动脉硬化）到重度钙化伴瓣叶运动受损（称为主动脉瓣狭窄）。在过去，由于瓣叶的时间依赖性磨损和撕裂以及被动钙沉积，该过程被认为是“退行性”的。成骨细胞在动脉粥样硬化血管病变和CAVD中的存在意味着钙化是一个类似于动脉粥样硬化的主动调节过程，伴有脂蛋白沉积和慢性炎症。如果钙化是活跃的，通过促成骨途径，可以预期钙化的发展和进展可以被抑制。与钙化性瓣膜病和动脉粥样硬化相关的临床因素的重叠进一步支持了共同的疾病机制。在我们最近的研究中，我们使用体外猪瓣膜间质细胞模型来研究自发性钙化和潜在的促进剂和抑制剂。使用该模型，我们发现Denosumab（一种靶向核因子-κB配体受体激活剂的人单克隆抗体）在50 μg/mL的工作浓度下可将诱导的钙沉积抑制至基础水平。
Calcification occurs in atherosclerotic vascular lesions and In the aortic valve. Calcific aortic valve disease (CAVD) is a slow, progressive disorder that ranges from mild valve thickening without obstruction of blood flow, termed aortic sclerosis, to severe calcification with impaired leaflet motion, termed aortic stenosis. In the past, this process was thought to be ‘degenerative’ because of time-dependent wear and tear of the leaflets, with passive calcium deposition. The presence of osteoblasts in atherosclerotic vascular lesions and in CAVD implies that calcification is an active, regulated process akin to atherosclerosis, with lipoprotein deposition and chronic inflammation. If calcification is active, via pro-osteogenic pathways, one might expect that development and progression of calcification could be inhibited. The overlap in the clinical factors associated with calcific valve disease and atherosclerosis provides further support for a shared disease mechanism. In our recent research we used an in vitro porcine valve interstitial cell model to study spontaneous calcification and potential promoters and inhibitors. Using this model, we found that denosumab, a human monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand may, at a working concentration of 50 μg/mL, inhibit induced calcium deposition to basal levels.