Pathologic Calcification of Adult Vascular Smooth Muscle Cells Differs on Their Crest or Mesodermal Embryonic Origin
Pathologic Calcification of Adult Vascular Smooth Muscle Cells Differs on Their Crest or Mesodermal Embryonic Origin
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DOI：
10.1002/jbmr.382
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发表时间：
2011-07-01
影响因子：
6.2
通讯作者：
Kempf, Herve
中科院分区：
文献类型：
--
作者：
Leroux-Berger, Margot;Queguiner, Isabelle;Kempf, Herve
血管钙化可发生在老年人和患有各种疾病的患者中。有趣的是，根据病理的不同，动脉系统的不同区域会受到影响。胚胎观察清楚地表明，血管平滑肌细胞（VSMC）的起源明显是异质的。例如，在主动脉中，生长在主动脉弓区的VSMCs来自心脏神经嵴细胞，而那些生长在降主动脉的VSMCs来自中胚层。我们在此研究了主动脉VSMCs的胚胎起源是否与它们的矿化能力相关。在高磷血症诱导血管钙化的条件下，我们对野生型小鼠进行了体外主动脉外植体培养和体外VSMC培养。我们的数据表明，VSMC胚胎起源影响其矿化能力。事实上，由神经嵴来源的VSMCs组成的主动脉弓中膜比由中胚层来源的VSMCs组成的降主动脉更早钙化。从两个主动脉区域采集的VSMCs也获得了类似的结果。我们还证明，在缺乏基质Gla蛋白（一种有效的钙化抑制剂）的小鼠模型中，病变在主动脉弓处开始发生广泛和自发的主动脉内侧钙化。随后，钙化在主动脉弓区域外进展，最终遍布整个动脉树，包括降主动脉。总之，我们的结果支持胚胎起源的VSMCs与钙化出现的时间之间的不可思议的相关性。(C) 2011年美国骨与矿物研究学会。
Vascular calcifications can occur in the elderly and in patients suffering from various diseases. Interestingly, depending on the pathology, different regions of the arterial system can be affected. Embryonic observations have clearly indicated that vascular smooth muscle cell (VSMC) origin is notably heterogeneous. For instance, in the aorta, VSMCs colonizing the aortic arch region derive from cardiac neural crest cells, whereas those populating the descending aorta derive from the mesoderm. We examined here whether the embryonic origin of aortic VSMCs would correlate with their ability to mineralize. Under hyperphosphatemic conditions that induce vascular calcifications, we performed ex vivo aortic explant cultures as well as in vitro VSMC cultures from wild-type mice. Our data showed that VSMC embryonic origin affects their ability to mineralize. Indeed, the aortic arch media made up of VSMCs of neural crest origin calcifies significantly earlier than the descending aorta composed of VSMCs, which are mesoderm-derived. Similar results were obtained with cultured VSMCs harvested from both aortic regions. We also demonstrated that in a mouse model deficient in matrix Gla protein, a potent calcification inhibitor, developing extensive and spontaneous medial calcifications of the aorta, lesions initiate in the aortic arch. Subsequently, calcifications progress outside the aortic arch region and ultimately spread all over the entire arterial tree, including the descending aorta. Altogether, our results support an unsuspected correlation between VSMCs of embryonic origin and the timing of appearance of calcifications. (C) 2011 American Society for Bone and Mineral Research.