Division of Nephrology, University Health Network, Toronto,Ontario, Canada.
Nephrol Dial Transplant. 2009 Dec;24(12):3867-71. doi: 10.1093/ndt/gfp495. Epub 2009 Sep 17.
Conventional haemodialysis (CHD) is associated with a reduction in vascular smooth muscle cells (VSMCs) proliferation and an increase in apoptosis.
VSMC proliferation, migration, apoptosis and Runx2 expression were assessed under normal conditions (n = 4) and before and after conversion from CHD to NHD (n = 15).
Compared to normal, CHD is associated with a reduction in VSMC proliferation [0.49 +/- 0.07 (CHD) versus 1.34 +/- 0.02 RFU, P < 0.01], an augmented caspase-3 activity [0.30 +/- 0.02 (CHD) versus 0.22 +/- 0.02 RFU, P = 0.014] and a 1.4 +/- 0.3 fold increase in Runx2 expression. After conversion to NHD, VSMC proliferation was higher than during CHD [from 0.49 +/- 0.07 (CHD) to 0.68 +/- 0.09 RFU, P = 0.006] and approached that of controls (1.34 +/- 0.02, P > 0.05). Caspase-3 activity was restored to similar values as controls [0.26 +/- 0.02 (NHD) versus 0.22 +/- 0.04 (normal), P > 0.05]. Runx2 expression decreased to similar levels as normal controls. NHD enhanced dialysis dose delivery, lowered blood pressure, plasma parathyroid hormone levels and normalized plasma phosphate (from 1.7 +/- 0.1 to 1.2 +/- 0.1 mmol/L, P < 0.01). The reduction in plasma phosphate correlated with the change in VSMC proliferation (r = -0.71, P = 0.007).
We demonstrate that NHD is associated with restoration of abnormal VSMC biology in ESRD. Given the increasing importance of VSMCs in the pathogenesis of atherosclerosis and medial calcification, these data may have important implications for vascular risk in ESRD patients.
常规血液透析(CHD)会导致血管平滑肌细胞(VSMCs)增殖减少和凋亡增加。
在正常情况下(n=4)以及从 CHD 转换为 NHD 之前和之后(n=15),评估 VSMC 增殖、迁移、凋亡和 Runx2 表达。
与正常情况相比,CHD 与 VSMC 增殖减少相关[0.49 +/- 0.07(CHD)与 1.34 +/- 0.02 RFU,P < 0.01],半胱天冬酶-3 活性增加[0.30 +/- 0.02(CHD)与 0.22 +/- 0.02 RFU,P = 0.014],Runx2 表达增加 1.4 +/- 0.3 倍。转换为 NHD 后,VSMC 增殖高于 CHD 时[从 0.49 +/- 0.07(CHD)到 0.68 +/- 0.09 RFU,P = 0.006],并接近对照[1.34 +/- 0.02,P > 0.05]。半胱天冬酶-3 活性恢复到与对照相似的值[0.26 +/- 0.02(NHD)与 0.22 +/- 0.04(正常),P > 0.05]。Runx2 表达降低到与正常对照相似的水平。NHD 增强了透析剂量的输送,降低了血压、甲状旁腺激素水平和使血浆磷酸盐正常化(从 1.7 +/- 0.1 到 1.2 +/- 0.1 mmol/L,P < 0.01)。血浆磷酸盐的减少与 VSMC 增殖的变化相关(r = -0.71,P = 0.007)。
我们证明 NHD 与 ESRD 中异常 VSMC 生物学的恢复有关。鉴于 VSMCs 在动脉粥样硬化和中膜钙化发病机制中的重要性日益增加,这些数据可能对 ESRD 患者的血管风险具有重要意义。