Inflammation and the osteogenic regulation of vascular calcification: a review and perspective.
Inflammation and the osteogenic regulation of vascular calcification: a review and perspective.
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DOI：
10.1161/hypertensionaha.109.134205
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Towler DA
中科院分区：
文献类型：
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作者：
Shao JS;Cheng SL;Sadhu J;Towler DA
动脉生物矿化过程已经折磨了人类5000年，2003年通过在蒂罗尔阿尔卑斯山发现的有趣的“冰木乃伊”Otzi的计算机断层成像实现了这一点。[1]在这位40岁的早期铜器时代的猎人的尸检中，可以很容易地检测到片状的腹部动脉粥样硬化钙化，这位猎人是2000年前图坦卡蒙国王的前身。1今天，血管钙化的流行病正在我们老龄化和代谢异常的人群中出现。虽然血管钙化曾经被认为只是死亡和垂死细胞的被动过程，但世界各地实验室的工作现在强调动脉生物矿化是钙化组织代谢的一种积极调节形式。4，5此外，在骨骼发育中，独特的生物学控制着膜骨、软骨内骨、牙本质和釉质中的基质矿化，6，7血管钙沉积的病理生物学存在机制多样性。2，4，5，8到目前为止，已经描述了五种常见的血管钙化形式，每种形式都具有独特的组织解剖学特征和临床背景，具有重叠但不同的分子机制4，5，9（表1）。虽然我们触及的主题，读者是指其他当代评论深入考虑致病差异。2，4，5在这篇简短的综述和展望中，我们回顾了最近的数据，强调炎症和氧化应激信号是血管矿物质沉积发病机制的关键因素。10此外，我们强调了低密度脂蛋白受体（LDLR）缺陷和载脂蛋白E（apoE）缺陷小鼠模型之间的差异（表2），这有助于阐明血脂异常、糖尿病和尿毒症对动脉钙沉积的多方面影响。2，4，11最后，我们总结了在制定治疗策略以解决日益困扰我们患者的血管钙化疾病负担时，考虑这些疾病阶段和特定背景对动脉矿化的贡献的重要性。五、十二
Arterial biomineralization processes have been afflicting humans for 5 millennia, as realized in 2003 via the computed tomographic imaging of Otzi, the intriguing “ice mummy” discovered in the Tyrolean Alps. 1 Patchy abdominal atherosclerotic calcification was readily detected in the postmortem of this 40-year–old hunter of the early Copper Age, by 2000 years a predecessor of King Tutankhamen. 1 Today, an epidemic of vascular calcification is emerging within our aging and dysmetabolic populace. 2, 3 Although vascular calcification was once considered only a passive process of dead and dying cells, work from laboratories worldwide has now highlighted that arterial biomineralization is an actively regulated form of calcified tissue metabolism. 4, 5 Moreover, as in skeletal development–where unique biology controls matrix mineralization in membranous bone, endochondral bone, dentin, and enamel, 6, 7 mechanistic diversity exists in the pathobiology of vascular calcium deposition. 2, 4, 5, 8 Five common forms of vascular calcification, each possessing unique histoanatomic characteristics and clinical settings with overlapping yet distinct molecular mechanisms, have been described to date4, 5, 9 (Table 1). Although we touch on the subject, the reader is referred to other contemporary reviews for in-depth consideration of pathogenic differences. 2, 4, 5 In this brief review and perspective, we recount recent data that emphasize inflammation and oxidative stress signaling as key contributors to the pathogenesis of vascular mineral deposition. 10 Furthermore, we highlight differences between the low-density lipoprotein receptor (LDLR)-deficient and apolipoprotein E (apoE)-deficient murine models (Table 2) that help articulate the multifaceted contributions of dyslipidemia, diabetes mellitus, and uremia to arterial calcium deposition. 2, 4, 11 We end by summarizing the importance of considering these disease stage-and context-specific contributions arterial mineralization when crafting therapeutic strategies to address the disease burden of vascular calcification that increasingly afflicts our patients. 5, 12