BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure
BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure
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DOI：
10.1097/01.asn.0000068404.57780.dd
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发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Hruska, KA
中科院分区：
文献类型：
--
作者：
Davies, MR;Lund, RJ;Hruska, KA
慢性肾衰竭并发心血管疾病死亡率高。造成这种死亡率的一个关键因素是血管钙化，目前尚无治疗方法。骨形态发生蛋白7是维持成人肾小管分化的重要肾形态原，在肾功能衰竭中下调。一些研究已经证明了它在治疗啮齿动物的各种肾脏疾病方面的功效，并且假设它也可以有效地治疗这种情况下的血管钙化。将尿毒症施加于低密度脂蛋白受体缺失的小鼠（动脉粥样硬化模型），然后用骨形态发生蛋白7治疗15周。尿毒症动物的组织学和化学分析显示血管钙化增加。治疗动物的钙化与未尿毒症对照动物相似或更少。血管壁上显示成骨细胞样表型的细胞可能是血管钙化的重要病因。骨钙素的表达被评估为成骨功能的标志物，结果表明，未经治疗的尿毒症动物的骨钙素表达增加，但在治疗后下调至与非尿毒症对照动物相似的水平。这些数据与骨形态发生蛋白7缺乏作为慢性肾衰竭的病理生理因素相一致，并且它们证明了其作为血管钙化的潜在治疗方法的有效性。
Chronic renal failure is complicated by high cardiovascular mortality. One key contributor to this mortality is vascular calcification, for which no therapy currently exists. Bone morphogenetic protein 7 is an essential renal morphogen that maintains renal tubular differentiation in the adult and is downregulated in renal failure. Several studies have demonstrated its efficacy in treating various renal diseases in rodents, and it was hypothesized that it would also be an effective treatment of vascular calcification in this setting. Uremia was imposed on LDL receptor null mice (a model of atherosclerosis), which were then treated with bone morphogenetic protein 7 for 15 wk. Uremic animals had increased vascular calcification by histology and chemical analysis. Calcification in treated animals was similar to or less than non-uremic control animals. Cells exhibiting an osteoblast-like phenotype in the vessel wall may be important in the etiology of vascular calcification. Expression of osteocalcin was assessed as a marker of osteoblastic function, and it is shown that it is increased in untreated uremic animals but downregulated to levels similar to non-uremic control animals with treatment. The data are compatible with bone morphogenetic protein 7 deficiency as a pathophysiologic factor in chronic renal failure, and they demonstrate its efficacy as a potential treatment of vascular calcification.