Ectopic vascular calcification associated with aging, diabetes mellitus, atherosclerosis, and chronic kidney disease is a considerable risk factor for cardiovascular events and death. Although vascular smooth muscle cells are primarily implicated in calcification, the role of progenitor cells is less known. In this study, we engineered tubular vascular tissues from embryonic multipotent mesenchymal progenitor cells either without differentiating or after differentiating them into smooth muscle cells and studied ectopic calcification through targeted gene analysis. Tissues derived from both differentiated and undifferentiated cells calcified in response to hyperphosphatemic inorganic phosphate (Pi) treatment suggesting that a single cell-type (progenitor cells or differentiated cells) may not be the sole cause of the process. We also demonstrated that Vitamin K, which is the matrix gla protein activator, had a protective role against calcification in engineered vascular tissues. Addition of partially-soluble elastin upregulated osteogenic marker genes suggesting a calcification process. Furthermore, partially-soluble elastin downregulated smooth muscle myosin heavy chain (Myh11) gene which is a late-stage differentiation marker. This latter point, in turn, suggests that SMC may be switching into a synthetic phenotype which is one feature of vascular calcification. Taken together, our approach presents a valuable tool to study ectopic calcification and associated gene expressions relevant to clinical therapeutic targets.

与衰老，糖尿病，动脉粥样硬化和慢性肾脏疾病相关的异位血管钙化是心血管事件和死亡的重要危险因素。尽管血管平滑肌细胞主要与钙化有关，但祖细胞的作用鲜为人知。在这项研究中，我们从胚胎多能间充质祖细胞中改造了管状血管组织，而未分化或将它们分化为平滑肌细胞，并通过靶向基因分析研究了异位钙化。来自分化细胞和未分化细胞的组织都响应高磷酸盐无机磷酸盐（Pi）处理而钙化，表明单一细胞类型（祖细胞或分化细胞）可能不是该过程的唯一原因。我们还证明了维生素K，它是基质gla蛋白激活剂，对工程血管组织中的钙化具有保护作用。添加部分可溶的弹性蛋白上调了成骨标记基因，提示钙化过程。此外，部分可溶的弹性蛋白下调了平滑肌肌球蛋白重链（Myh11）基因是晚期分化标记。反过来，这后一点表明SMC可能正在转变成合成表型，这是血管钙化的特征之一。综上所述，我们的方法为研究异位钙化和与临床治疗靶标相关的相关基因表达提供了一种有价值的工具。