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Review
. 2018 May 29;10(6):218.
doi: 10.3390/toxins10060218.

The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function

Lucie Hénaut  1 , Aurélien Mary  2   3 , Jean-Marc Chillon  4   5 , Saïd Kamel  6   7 , Ziad A Massy  8   9
Affiliations
Review

The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function

Lucie Hénaut et al. Toxins (Basel). .

Abstract

Chronic kidney disease (CKD) is associated with profound vascular remodeling, which accelerates the progression of cardiovascular disease. This remodeling is characterized by intimal hyperplasia, accelerated atherosclerosis, excessive vascular calcification, and vascular stiffness. Vascular smooth muscle cell (VSMC) dysfunction has a key role in the remodeling process. Under uremic conditions, VSMCs can switch from a contractile phenotype to a synthetic phenotype, and undergo abnormal proliferation, migration, senescence, apoptosis, and calcification. A growing body of data from experiments in vitro and animal models suggests that uremic toxins (such as inorganic phosphate, indoxyl sulfate and advanced-glycation end products) may directly impact the VSMCs' physiological functions. Chronic, low-grade inflammation and oxidative stress-hallmarks of CKD-are also strong inducers of VSMC dysfunction. Here, we review current knowledge about the impact of uremic toxins on VSMC function in CKD, and the consequences for pathological vascular remodeling.

Keywords: chronic kidney disease; uremic toxins; vascular smooth muscle cells.

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Conflict of interest statement

Z.A. Massy reports grants for CKD REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp and Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka and the French government, as well as fees and grants to charities from Amgen, Bayer, and Sanofi-Genzyme. These sources of funding are not necessarily related to the content of the present manuscript. L. Hénaut, A. Mary, J.M. Chillon and S. Kamel declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
A schematic view of the impact of uremic toxins on VSMC cell function and then vascular function. VSMC: vascular smooth muscle cell.
See this image and copyright information in PMC

References

    1. Lacolley P., Regnault V., Segers P., Laurent S. Vascular Smooth Muscle Cells and Arterial Stiffening: Relevance in Development, Aging, and Disease. Physiol. Rev. 2017;97:1555–1617. doi: 10.1152/physrev.00003.2017. - DOI - PubMed
    1. Owens G.K. Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 1995;75:487–517. doi: 10.1152/physrev.1995.75.3.487. - DOI - PubMed
    1. Bennett M.R., Sinha S., Owens G.K. Vascular Smooth Muscle Cells in Atherosclerosis. Circ. Res. 2016;118:692–702. doi: 10.1161/CIRCRESAHA.115.306361. - DOI - PMC - PubMed
    1. Go A.S., Chertow G.M., Fan D., McCulloch C.E., Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 2004;351:1296–1305. doi: 10.1056/NEJMoa041031. - DOI - PubMed
    1. Brunet P., Gondouin B., Duval-Sabatier A., Dou L., Cerini C., Dignat-George F., Jourde-Chiche N., Argiles A., Burtey S. Does uremia cause vascular dysfunction? Kidney Blood Press Res. 2011;34:284–290. doi: 10.1159/000327131. - DOI - PubMed

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