背景――血管钙化与V期肾病的发病率和死亡率升高有关，但对其在体内的早期发病机理和始动机制了解尚少。为了阐明这个问题，我们测定了儿童（10例透析前的儿童，24例透析的儿童）动脉的钙负荷，并将钙负荷与临床、生化和血管测定结果关联起来。

方法和结果――血管钙负荷在透析前和透析儿童中明显升高，并与患者的平均血清Caxphosphate产物相关。但是仅透析患者颈动脉内中膜厚度升高，动脉硬度增加，CT所示的钙化仅见于2例钙负荷最高的患者。重要的是，透析前血管的组织学没有发生变化，而透析血管表现出凋亡导致的广泛血管平滑肌细胞（VSMC）减少的证据。透析血管也出现碱性磷酸酶活性升高以及Runx2和osterix表达，提示VSMC的成骨性转变。透析血管中囊泡膜标志物膜联蛋白VI以及囊泡成分矿化抑制剂胎球蛋白-A和基质Gla-蛋白的沉积增加，而且早于von Kossa染色阳性的明显钙化。电镜检查表明受损/死亡的VSMCs释放的囊泡中有羟基磷灰石纳米微晶，提示其在引起钙化中的作用。

结论――总之，本研究表明钙沉积开始于透析前，但透析中VSMC凋亡的诱导是引起VSMC防御机制失效和导致明显钙化的关键事件，最终导致临床上可检测的血管损伤。因此确定导致透析中VSMC死亡的因素对预防血管钙化非常重要。

来源：丁香园

Dialysis Accelerates Medial Vascular Calcification in Part by Triggering Smooth Muscle Cell Apoptosis

Background— Vascular calcification is associated with increased morbidity and mortality in stage V chronic kidney disease, yet its early pathogenesis and initiating mechanisms in vivo remain poorly understood. To address this, we quantified the calcium (Ca) load in arteries from children (10 predialysis, 24 dialysis) and correlated it with clinical, biochemical, and vascular measures.

Methods and Results— Vessel Ca load was significantly elevated in both predialysis and dialysis and was correlated with the patients’ mean serum Caxphosphate product. However, only dialysis patients showed increased carotid intima-media thickness and increased aortic stiffness, and calcification on computed tomography was present in only the 2 patients with the highest Ca loads. Importantly, predialysis vessels appeared histologically intact, whereas dialysis vessels exhibited evidence of extensive vascular smooth muscle cell (VSMC) loss owing to apoptosis.Dialysis vessels also showed increased alkaline phosphatase activity and Runx2 and osterix expression, indicative of VSMC osteogenic transformation. Deposition of the vesicle membrane marker annexin VI and vesicle component mineralization inhibitors fetuin-A and matrix Gla-protein increased in dialysis vessels and preceded von Kossa positive overt calcification. Electron microscopy showed hydroxyapatite nanocrystals within vesicles released from damaged/dead VSMCs, indicative of their role in initiating calcification.

Conclusions— Taken together, this study shows that Ca accumulation begins predialysis, but it is the induction of VSMC apoptosis in dialysis that is the key event in disabling VSMC defense mechanisms and leading to overt calcification, eventually with clinically detectable vascular damage. Thus the identification of factors that lead to VSMC death in dialysis will be of prime importance in preventing vascular calcification.

source：Circulation.com