Diabetes and Vascular Calcification
Diabetes and Vascular Calcification
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DOI：
10.1007/978-981-10-4376-5_5
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
K. Mori;M. Inaba
中科院分区：
文献类型：
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作者：
K. Mori;M. Inaba
血管钙化一直被认为是一种被动的、退行性的过程，但最近的研究结果表明，它像成骨一样受到积极的调控。此外，血管钙化大致分为两种类型：内膜动脉钙化(IAC)和中层动脉钙化(MAC)。IAC通常与动脉粥样硬化有关，而MAC通常与衰老、糖尿病和慢性肾脏疾病有关。虽然MAC不会直接导致狭窄或闭塞病变，但它可能会加剧动脉僵硬，导致显著的血流动力学变化，导致心血管死亡。血管平滑肌细胞(VSMCs)的转分化和细胞外基质(ECM)的改变，主要是由于弹性蛋白的降解，参与了MAC的发生和发展。特别是，矮小相关转录因子2(Runx2)似乎在VSMCs从血管收缩表型向成骨细胞样表型转化过程中起着关键作用。糖尿病的存在通过上调Runx2促进VSMC转分化，并通过金属蛋白酶诱导弹性蛋白降解促进ECM改变。胎球蛋白-A不仅可以作为胰岛素抵抗的诱导剂，还可以通过形成钙蛋白颗粒(CPPs)抑制异位钙化。最近，有假说认为CPPs的过度生产可能会导致血管损伤，包括血管钙化。由于胎球蛋白-A与糖尿病和血管钙化有关，对胎球蛋白的精确研究可能会给这一领域带来新的见解。
Vascular calcification had been accepted as a passive, degenerative process, but recent findings suggested that it is actively regulated like osteogenesis. In addition, vascular calcification is roughly classified into two types: intimal arterial calcification (IAC) and medial arterial calcification (MAC). IAC is usually associated with atherosclerosis, whereas MAC is often associated with aging, diabetes, and chronic kidney disease. Although MAC does not directly cause stenotic or occlusive lesions, it may exacerbate arterial stiffness with significant hemodynamic changes, resulting in cardiovascular mortality. Transdifferentiation of vascular smooth muscle cells (VSMCs) and changes in extracellular matrix (ECM), which are mainly due to elastin degradation, are involved in the onset and progression of MAC. In particular, runt-related transcription factor 2 (Runx2) seems to play a critical role in the transformation of VSMCs from a vascular contractile phenotype into an osteoblast-like phenotype. The presence of diabetes accelerates both VSMC transdifferentiation through the upregulation of Runx2 and ECM changes by metalloproteinase-induced elastin degradation. Fetuin-A can act as not only an inducer of insulin resistance but also as an inhibitor of ectopic calcification through the formation of calciprotein particles (CPPs). Recently, it has been hypothesized that overproduction of CPPs could cause vascular damage, including vascular calcification. Since fetuin-A is involved in both diabetes and vascular calcification, precise investigation of CPPs may give new insights in this field.