Department of Cardiovasology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):261-6. doi: 10.1016/j.bbrc.2009.11.046. Epub 2009 Nov 11.
Chronic renal failure (CRF) markedly accelerates the development of atherosclerosis, but the pathogenesis of uremic atherosclerosis remains to be elucidated. The klotho gene, predominantly expressed in the kidney, plays a key role in regulating aging and the development of age-related diseases in mammals. A loss of klotho results in multiple aging-like phenotypes including atherosclerosis. This study examines the relationship between the klotho expression and the development of accelerated atherosclerosis in uremic state. Eight-week-old apolipoprotein E-deficient (apo-E(-/-)) male mice underwent 5/6 partial kidney ablation to induce CRF or sham-operation. At 6 wk after nephrectomy, CRF mice showed significantly increased aortic plaque area fraction, aortic root plaque area and aortic cholesterol content as compared with non-CRF mice. Serum urea, total cholesterol and triglyceride concentrations were significantly higher in CRF apo-E(-/-) mice compared with non-CRF controls. Moreover, the expression of renal klotho gene and the serum levels of klotho protein were markedly decreased in CRF mice compared with controls. These results suggested that CRF favored atherosclerosis in apo-E(-/-) mice and uremic atherosclerosis was accompanied by down-regulation of klotho expression.
慢性肾衰竭（CRF）显著加速了动脉粥样硬化的发展，但尿毒症性动脉粥样硬化的发病机制仍有待阐明。klotho 基因主要在肾脏中表达，在调节哺乳动物的衰老和与年龄相关疾病的发展中起着关键作用。klotho 的缺失会导致多种类似衰老的表型，包括动脉粥样硬化。本研究探讨了 klotho 表达与尿毒症状态下加速动脉粥样硬化发展之间的关系。8 周龄载脂蛋白 E 缺陷（apo-E（-/-））雄性小鼠接受 5/6 部分肾切除术以诱导 CRF 或假手术。肾切除术 6 周后，与非 CRF 小鼠相比，CRF 小鼠的主动脉斑块面积分数、主动脉根部斑块面积和主动脉胆固醇含量显著增加。与非 CRF 对照组相比，CRF apo-E（-/-）小鼠的血清尿素、总胆固醇和甘油三酯浓度显著升高。此外，与对照组相比，CRF 小鼠的肾脏 klotho 基因表达和血清 klotho 蛋白水平明显降低。这些结果表明，CRF 促进了 apo-E（-/-）小鼠的动脉粥样硬化，尿毒症性动脉粥样硬化伴随着 klotho 表达的下调。
