Division of Nephrology, International Medical Center of Japan, Wakayama Medical University, Wakayama, Japan.
Ren Fail. 2010 Jan;32(2):214-23. doi: 10.3109/08860220903367544.
Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown.
We produced a rat model for vascular calcification with hyperphosphatasemia and hyperparathyroidism, performing a 5/6 nephrectomy and providing a high-phosphorus, low-calcium diet for eight weeks. We examined mRNA obtained from the calcified aortae using microarray analysis, and searched for alterations in gene expression specifically in the calcified lesions.
Medial calcification was demonstrated in the abdominal aorta of 12 out of 42 hyperparathyroidism rats. In the aortae of hyperparathyroid rats with vascular calcification, the genes for heparan sulfate proteoglycans, including perlecan, were found to be down-regulated using microarray analysis and real time PCR. Immunohistochemistry also demonstrated reduced production of perlecan in the aortae of hyperparathyroid rats.
Perlecan is a major component of the vascular wall basement membrane and may play a role in protecting vascular smooth muscle cells from inflammatory cells and various toxins. It has also been reported that heparan sulfate chains may inhibit osteogenesis. Our findings indicate that perlecan may protect vascular smooth muscle cells from various factors that promote vascular calcification.
It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification.
血管钙化是一种重要的并发症，会使透析患者的预后恶化，尽管其详细的分子机制尚不清楚。
我们通过高磷血症和甲状旁腺功能亢进症制造了一种血管钙化大鼠模型，进行了 5/6 肾切除术，并提供了高磷、低钙饮食 8 周。我们使用微阵列分析检查了钙化主动脉中的 mRNA，并专门搜索了钙化病变中基因表达的变化。
在 42 只甲状旁腺功能亢进症大鼠中，有 12 只大鼠的腹主动脉出现了中层钙化。在用微阵列分析和实时 PCR 分析时发现，在甲状旁腺功能亢进症大鼠的钙化主动脉中，硫酸乙酰肝素蛋白聚糖的基因，包括核心蛋白聚糖，其表达下调。免疫组织化学也表明甲状旁腺功能亢进症大鼠的主动脉中核心蛋白聚糖的产生减少。
核心蛋白聚糖是血管壁基底膜的主要成分，可能在保护血管平滑肌细胞免受炎症细胞和各种毒素的侵害方面发挥作用。也有报道称，硫酸乙酰肝素链可能抑制成骨作用。我们的研究结果表明，核心蛋白聚糖可能保护血管平滑肌细胞免受促进血管钙化的各种因素的侵害。
甲状旁腺功能亢进症大鼠钙化主动脉中核心蛋白聚糖表达减少可能是血管钙化的一个危险因素。
