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Editorial
. 2019 Jan 2;139(1):97-100.
doi: 10.1161/CIRCULATIONAHA.118.037308.

Uremic Toxins Activate Macrophages

Friedrich F Hoyer  1 , Matthias Nahrendorf  1   2
Affiliations
Editorial

Uremic Toxins Activate Macrophages

Friedrich F Hoyer et al. Circulation. .
No abstract available

Keywords: Editorials; atherosclerosis; chronic kidney disease; inflammation; macrophages; myeloid cells; uremic toxins.

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Conflict of interest statement

Disclosures

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
The uremic toxin indoxyl sulfate accumulates in patients with chronic kidney disease on hemodialysis. Macrophages in atherosclerotic lesions take up indoxyl sulfate via OATP2B1. Indoxyl sulfate increases USP5 which inhibits the ubiquitin proteasome pathway. Dll4 levels increase due to impaired degradation and activate NOTCH receptors on macrophages in proximity. NOTCH-ICD translocates into the nucleus and induces transcription of proinflammatory cytokines, which further aggravate atherosclerotic lesion development. OATP2B1: Organic anion transporting polypeptide P2B1. USP5: Ubiquitin specific peptidase 5. UPP: Ubiquitin proteasome pathway. Dll4: Delta-like ligand 4. ICD: Intracellular domain. IL1β: Interleukin 1-beta. MCP1: Monocyte chemoattractant protein 1.
See this image and copyright information in PMC

Comment on

References

    1. Tonelli M, Karumanchi SA, Thadhani R. Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease. Circulation. 2016;133:518–536. - PubMed
    1. Saran R, Robinson B, Abbott KC, Agodoa LYC, Bhave N, Bragg-Gresham J, Balkrishnan R, Dietrich X, Eckard A, Eggers PW, Gaipov A, Gillen D, Gipson D, Hailpern SM, Hall YN, Han Y, He K, Herman W, Heung M, Hirth RA, Hutton D, Jacobsen SJ, Jin Y, Kalantar-Zadeh K, Kapke A, Kovesdy CP, Lavallee D, Leslie J, McCullough K, Modi Z, Molnar MZ, Montez-Rath M, Moradi H, Morgenstern H, Mukhopadhyay P, Nallamothu B, Nguyen DV, Norris KC, O’Hare AM, Obi Y, Park C, Pearson J, Pisoni R, Potukuchi PK, Rao P, Repeck K, Rhee CM, Schrager J, Schaubel DE, Selewski DT, Shaw SF, Shi JM, Shieu M, Sim JJ, Soohoo M, Steffick D, Streja E, Sumida K, Tamura MK, Tilea A, Tong L, Wang D, Wang M, Woodside KJ, Xin X, Yin M, You AS, Zhou H, Shahinian V. US Renal Data System 2017 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2018;71:A7. - PMC - PubMed
    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305. - PubMed
    1. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, Matsushita K, Wen CP. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–352. - PubMed
    1. Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, Ritz E, German DADSI. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–248. - PubMed