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Hemodialysis Serum Stimulates the TXNIP-eNOS-STAT3 Inflammatory Pathway In Vitro

Keren Cohen-Hagai1,2, Hadil Kashua3, Sydney Benchetrit1,2

  • 1Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba 44281, Israel.

Antioxidants (Basel, Switzerland)
|May 27, 2023
PubMed

Insights

Sera from hemodialysis patients activate a new inflammatory pathway involving TXNIP, STAT3, and reduced eNOS in endothelial cells. This occurs independently of patient nutritional status, highlighting a key mechanism in kidney disease complications.

Area of Science:

  • Cardiovascular Biology
  • Nephrology
  • Molecular Medicine

Background:

  • Chronic kidney disease (CKD) is associated with endothelial dysfunction, vascular inflammation, and atherosclerosis.
  • Hemodialysis (HD) patients face increased morbidity and mortality due to impaired kidney function, malnutrition, and oxidative stress.
  • TXNIP and STAT3 are implicated in oxidative stress, inflammation, and endothelial dysfunction, contributing to atherosclerosis.

Purpose of the Study:

  • To investigate the impact of sera from HD patients on the TXNIP-eNOS-STAT3 pathway in human umbilical vein endothelial cells (HUVECs).
  • To elucidate the role of HD patient sera in endothelial cell inflammation and dysfunction.

Main Methods:

  • HUVECs were exposed to serum from HD patients or healthy controls for 24 hours.
  • mRNA and protein expression levels of key inflammatory and endothelial markers were analyzed.
  • Patient nutritional status was assessed using malnutrition-inflammation scores.

Main Results:

  • HD patient serum significantly increased TXNIP, IL-8, and STAT3 expression in HUVECs.
  • eNOS, SOCS3, and SIRT1 expression were decreased in HUVECs treated with HD serum.
  • The observed inflammatory changes were independent of the patients' nutritional status.

Conclusions:

  • Sera from hemodialysis patients induce a novel inflammatory pathway in endothelial cells.
  • This pathway involves upregulation of TXNIP and STAT3 and downregulation of eNOS.
  • The inflammatory effects are not influenced by the nutritional status of HD patients.
Abstract

Keywords:
HUVECSTAT3TXNIPeNOShemodialysisinflammatory response

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