Arterial calcification in chronic kidney disease: key roles for calcium and phosphate.
Arterial calcification in chronic kidney disease: key roles for calcium and phosphate.
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DOI：
10.1161/circresaha.110.234914
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发表时间：
2011-09-02
影响因子：
20.1
通讯作者：
Giachelli CM
中科院分区：
文献类型：
--
作者：
Shanahan CM;Crouthamel MH;Kapustin A;Giachelli CM
血管钙化是慢性肾脏病(CKD)患者心血管死亡的高危因素。钙(Ca)和磷(P)代谢紊乱在CKD患者中很常见，并导致血管钙化。本文就钙磷稳态的生理调节机制及其在慢性肾脏病中失调的基础作一综述。此外，我们重点介绍了最近的研究结果，这些发现表明，升高的钙和磷对促进血管钙化的血管平滑肌细胞(VSMCs)具有直接影响，包括刺激骨/软骨细胞分化、囊泡释放、细胞凋亡、抑制物丢失和ECM基质降解。这些研究表明，P升高在促进VSMC向骨/软骨分化中起主要作用，而Ca升高在促进VSMC凋亡和囊泡释放中起主要作用。此外，钙和磷升高的影响是协同作用的，为慢性肾脏病的血管钙化提供了主要刺激。揭开钙和磷对VSMCs影响的复杂调控通路，最终将为限制CKD患者血管钙化的破坏性影响提供新的靶点和治疗方法。
Vascular calcification contributes to the high risk of cardiovascular mortality in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and phosphate (P) metabolism is common in CKD patients, and drives vascular calcification. In this article, we review the physiological regulatory mechanisms for Ca and P homeostasis and the basis for their dysregulation in CKD. In addition, we highlight recent findings indicating that elevated Ca and P have direct effects on vascular smooth muscle cells (VSMCs) that promote vascular calcification, including stimulation of osteo/chondrogenic differentiation, vesicle release, apoptosis, loss of inhibitors, and ECM matrix degradation. These studies suggest a major role for elevated P in promoting osteo/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release. Furthermore, the effects of elevated Ca and P are synergistic providing a major stimulus for vascular calcification in CKD. Unravelling the complex regulatory pathways that mediate the effects of both Ca and P on VSMCs will ultimately provide novel targets and therapies to limit the destructive effects of vascular calcification in CKD patients.