Early Vascular Ageing and Cellular Senescence in Chronic Kidney Disease

被引:71
作者
Dai, Lu [1 ]
Qureshi, Abdul Rashid [1 ]
Witasp, Anna [1 ]
Lindholm, Bengt [1 ]
Stenvinkel, Peter [1 ]
机构
[1] Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Campus Flemingsberg, Stockholm, Sweden
基金
欧盟地平线“2020”; 瑞典研究理事会;
关键词
Chronic kidney disease; Early vascular ageing; Vascular calcification; Senescence; Senolytic drugs; ARTERIAL MEDIAL CALCIFICATION; SMOOTH-MUSCLE-CELLS; DNA-DAMAGE RESPONSE; FETUIN-A LEVELS; SECRETORY PHENOTYPE; OXIDATIVE STRESS; CALCIPROTEIN PARTICLES; UP-REGULATION; INFLAMMATION; EXPRESSION;
D O I
10.1016/j.csbj.2019.06.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic kidney disease (CKD) is a dinical model of premature ageing characterized by progressive vascular disease, systemic inflammation, muscle wasting and frailty. The predominant early vascular ageing (EVA) process mediated by medial vascular calcification (VC) results in a marked discrepancy between chronological and biological vascular age in CKD. Though the exact underlying mechanisms of VC and EVA are not fully elucidated, accumulating evidence indicates that cellular senescence - and subsequent chronic inflammation through the senescence-associated secretary phenotype (SASP) - plays a fundamental role in its initiation and progression. In this review, we discuss the pathophysiological links between senescence and the EVA process in CKD, with focus on cellular senescence and media VC, and potential anti-ageing therapeutic strategies of senolytic drugs targeting cellular senescence and EVA in CKD. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
引用
收藏
页码:721 / 729
页数:9
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