Nitschke Yvonne, Rutsch Frank
Department of General Pediatrics, Munster University Children's Hospital, Albert-Schweitzer-Campus 1, D-48149 Munster, Germany.
Curr Pharm Des. 2014;20(37):5839-52. doi: 10.2174/1381612820666140212193330.
In recent years, mechanisms of arterial calcifications are beginning to be elucidated. Arterial calcification is now considered as an actively regulated process resembling osteogenesis within the arterial wall orchestrated by a number of systemic or constitutively expressed mediators. Genetic studies of rare monogenic human disorders and studies of naturally occurring or mutant mouse models have identified specific inductors and inhibitors of arterial calcification, which can be classified according to the networks they participate in. These networks include ATP and pyrophosphate metabolism, phosphate homeostasis and vitamin D receptor signaling. Furthermore, intracellular signaling molecules, including SMAD6 and a number of systemic circulatory inhibitors of arterial calcification, including fetuin, tumor necrosis factor receptor superfamily member 11b, matrix GLA protein, adiponectin and family with sequence similarity 20 member A have been identified by human and mouse genetics. Based on the in vivo evidence of their functional relevance, these proteins will serve as excellent targets for the prevention and treatment of arterial calcification. In this review we discuss the functional role of the identified modulators of arterial calcification and describe the networks they belong to.
近年来，动脉钙化的机制开始得到阐明。动脉钙化现在被认为是一个受主动调控的过程，类似于动脉壁内由多种全身或组成性表达的介质精心编排的骨生成过程。对罕见单基因人类疾病的遗传学研究以及对天然存在或突变小鼠模型的研究已经确定了动脉钙化的特定诱导剂和抑制剂，它们可以根据所参与的网络进行分类。这些网络包括ATP和焦磷酸代谢、磷酸盐稳态以及维生素D受体信号传导。此外，通过人类和小鼠遗传学已经鉴定出细胞内信号分子，包括SMAD6以及多种动脉钙化的全身循环抑制剂，包括胎球蛋白、肿瘤坏死因子受体超家族成员11b、基质GLA蛋白、脂联素和序列相似性家族20成员A。基于它们在体内功能相关性的证据，这些蛋白质将成为预防和治疗动脉钙化的理想靶点。在这篇综述中，我们讨论了已确定的动脉钙化调节因子的功能作用，并描述了它们所属的网络。
