Inflammatory, metabolic, and genetic mechanisms of vascular calcification.
Inflammatory, metabolic, and genetic mechanisms of vascular calcification.
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DOI：
10.1161/atvbaha.113.302070
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Tintut Y
中科院分区：
文献类型：
--
作者：
Demer LL;Tintut Y
本文就血管钙化的最新研究进展作一综述。这种病理通过对血管顺应性、血管运动以及最有可能的斑块稳定性产生不利的机械影响，导致大量心血管疾病的发病率和死亡率。生物矿化是一个复杂的、受调控的过程，在自然界中广泛存在。几十年前，它在血管系统中的存在被认为是一种纯粹的好奇心，是一种不受监管的、不涉及生物机制的“营养不良”过程。虽然这一过程是否具有适应价值或过去的进化优势仍然存在争议，但在理解推动这一过程的生物学机制方面已经取得了实质性进展。不同类型的钙性血管病变，如炎症性和代谢性，在骨骼钙化中有类似的机制，如膜内和软骨内骨化。最近的工作已经确定了炎症、氧化脂质、弹性蛋白、碱性磷酸酶、骨祖细胞、基质γ-羧谷氨酸蛋白(MGP)、谷氨酰胺转氨酶、破骨调节因子、磷酸调节激素和受体、细胞凋亡、前层蛋白A、自噬以及类似于骨骼基质囊泡的微泡或微粒的重要调节作用。最近的工作揭示了MGP、维生素K、华法林和运输蛋白之间有趣的相互作用。最后，最近在遗传形式的钙化性血管病变方面的突破，已经确定了负责的基因以及意想不到的表型重叠。
This review centers on updating the active research area of vascular calcification. This pathology underlies substantial cardiovascular morbidity and mortality, through adverse mechanical effects on vascular compliance, vasomotion, and, most likely, plaque stability. Biomineralization is a complex, regulated process occurring widely throughout nature. Decades ago, its presence in the vasculature was considered a mere curiosity and an unregulated, “dystrophic” process that does not involve biological mechanisms. While it remains controversial whether the process has any adaptive value or past evolutionary advantage, substantial advances have been made in understanding the biological mechanisms driving the process. Different types of calcific vasculopathy, such as inflammatory vs. metabolic, have parallel mechanisms in skeletal bone calcification, such as intramembranous and endochondral ossification. Recent work has identified important regulatory roles for inflammation, oxidized lipids, elastin, alkaline phosphatase, osteoprogenitor cells, matrix gamma-carboxyglutamic acid protein (MGP), transglutaminase, osteoclastic regulatory factors, phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy, and microvesicles or microparticles similar to the matrix vesicles of skeletal bone. Recent work has uncovered fascinating interactions between MGP, vitamin K, warfarin and transport proteins. And, lastly, recent breakthroughs in inherited forms of calcific vasculopathy, have identified the genes responsible as well as an unexpected overlap of phenotypes.