Effect of endoplasmic reticulum stress on endothelial ischemia-reperfusion injury in humans

Holden W. Hemingway, Amy M. Moore, Albert H. Olivencia-Yurvati, Steven A. Romero

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Endoplasmic reticulum stress contributes to ischemia-reperfusion (I/R) injury in rodent and cell models. However, the contribution of endoplasmic reticulum stress in the pathogenesis of endothelial I/R injury in humans is unknown. We tested the hypothesis that compared with placebo, inhibition of endoplasmic reticulum stress via ingestion of tauroursodeoxycholic acid would prevent the attenuation of endothelium-dependent vasodilation following I/R injury. Twelve young adults (6 women) were studied following ingestion of a placebo or 1,500 mg tauroursodeoxycholic acid (TUDCA). Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasonography) before and after I/R injury, which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Endothelium-independent vasodilation (glyceryl trinitrate-mediated vasodilation) was also assessed after I/R injury. Compared with placebo, TUDCA ingestion increased circulating plasma concentrations by 145±90 ng/ml and increased concentrations of the taurine unconjugated form, ursodeoxycholic acid, by 560±156 ng/ml (both P < 0.01). Ischemia-reperfusion injury attenuated endothelium-dependent vasodilation, an effect that did not differ between placebo (pre-I/R, 5.0±2.1% vs. post-I/R, 3.5±2.2%) and TUDCA (pre-I/R, 5.6 ± 2.1% vs. post-I/R, 3.9±2.1%; P = 0.8) conditions. Similarly, endothelium-independent vasodilation did not differ between conditions (placebo, 19.6±4.8% vs. TUDCA, 19.7±6.1%; P = 0.9). Taken together, endoplasmic reticulum stress does not appear to contribute to endothelial I/R injury in healthy young adults.

Original languageEnglish
Pages (from-to)R666-R672
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume319
Issue number6
DOIs
StatePublished - 4 Dec 2020

Keywords

  • Endoplasmic reticulum stress
  • Flow-mediated dilation
  • Ischemia-reperfusion
  • Tauroursodeoxycholic acid

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