Kurabayashi Masahiko
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Japan.
Clin Calcium. 2015 May;25(5):661-9.
Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.
血管钙化常见于衰老、慢性肾脏病（CKD）、糖尿病和动脉粥样硬化，且与心血管疾病的发病率和死亡率密切相关。长期以来，血管钙化一直被视为动脉壁退变和坏死的终末阶段，是一个被动的、不受调控的过程。然而，现在已知它是一个活跃且受到严格调控的过程，涉及类似于骨矿化的血管平滑肌细胞（VSMC）表型转变。简而言之，动脉粥样硬化斑块中的钙沉积物由羟基磷灰石组成，可能与完全形成的板层骨看起来相同。通过使用遗传命运图谱策略，血管中层的VSMC产生了在MGP（- / -）小鼠钙化动脉中层中观察到的大多数成骨软骨前体细胞和软骨样细胞。VSMC的成骨分化以包括骨形态发生蛋白（BMP）-2、Msx2和骨桥蛋白等骨相关分子的表达为特征，这些分子由成骨细胞和软骨细胞产生。我们最近的发现是：（i）Runx2和Notch1诱导成骨分化，以及（ii）晚期糖基化终产物（AGE）/AGE受体（RAGE）和棕榈酸促进VSMC的成骨分化。目前对血管钙化分子机制的理解正处于深入研究阶段。
