Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding

Jiyeon Ko, Hyun Jung Kang, Dal Ah Kim, Mi Jin Kim, Eun Sun Ryu, Shina Lee, Jung Hwa Ryu, Carlos Roncal, Richard J. Johnson, Duk Hee Kang

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA-induced glycocalyx shedding and EndoMT. Antioxidants including N-acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of α-smooth muscle actin in PTCs. Plasma level of syndecan-1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA-induced endothelial dysfunction and kidney disease.—Ko, J., Kang, H.-J., Kim, D.-A., Kim, M.-J., Ryu, E.-S., Lee, S., Ryu, J.-H., Roncal, C., Johnson, R. J., Kang, D.-H. Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding. FASEB J. 33, 13334–13345 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)13334-13345
Number of pages12
JournalFASEB Journal
Volume33
Issue number12
DOIs
StatePublished - Dec 2019

Keywords

  • EndoMT
  • hyperuricemia
  • reactive oxygen species
  • syndecan-1

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