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Am J Physiol Heart Circ Physiol. 2017 Jul 1;313(1):H1-H13. doi: 10.1152/ajpheart.00787.2016. Epub 2017 Apr 14.

Vasculopathy in the setting of cardiorenal syndrome: roles of protein-bound uremic toxins.

Guo J1,2,3, Lu L1,4, Hua Y1,4, Huang K1, Wang I5, Huang L1, Fu Q2,3, Chen A2,3, Chan P6,7, Fan H6, Liu ZM6, Wang BH5.

Author information

1
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
2
Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
3
Guangdong Provincial Center of Biomedical Engineering for Cardiovascular Diseases, Guangzhou, China.
4
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
5
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; bing.wang@monash.edu.
6
Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai, China; and.
7
Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

Abstract

Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), while CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neurohormonal, mechanical, and biochemical factors, nondialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo, and clinical observations. PBUTs are ineffectively removed by hemodialysis because their complexes with albumins are larger than the pores of the dialysis membranes. PBUTs such as indoxyl sulfate and p-cresyl sulfate are key determinate and predictive factors for the progression of CVD in CKD patients. In CRS, both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) exhibit significant dysfunction that is associated with the progression of CVD. PBUTs influence proliferation, calcification, senescence, migration, inflammation, and oxidative stress in VSMCs and ECs through various mechanisms. These pathological changes lead to arterial remodeling, stiffness, and atherosclerosis and thus reduce heart perfusion and impair left ventricular function, aggravating CRS. There is limited literature about the effect of PBUT on the vascular system and their contribution to CRS. This review summarizes current knowledge on how PBUTs influence vasculature, clarifies the relationship between uremic toxin-related vascular disease and CRS, and highlights the potential therapeutic strategies of uremic vasculopathy in the setting of CRS.

KEYWORDS:

cardiorenal syndrome; endothelial cells; protein-bound uremic toxins; vascular smooth muscle cells; vasculopathy

PMID:
28411233
DOI:
10.1152/ajpheart.00787.2016
[Indexed for MEDLINE]
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