The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Ilias Attaye, Yvo M Smulders, Monique C de Waard, Heleen M Oudemans-van Straaten, Bob Smit, Michiel H Van Wijhe, Rene J Musters, Pieter Koolwijk, Angelique M E Spoelstra-de Man

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BACKGROUND: Hyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC).

METHODS: hMVEC of the systemic circulation were exposed to graded oxygen fractions of 20, 30, 50, and 95% O2for 8, 24, and 72 h. These fractions correspond to 152, 228, 380, and 722 mmHg, respectively. Cell proliferation and viability was measured via a proliferation assay, peroxynitrite formation via anti-nitrotyrosine levels, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) levels via q-PCR and western blot analysis.

RESULTS: Exposing hMVEC to 50 and 95% O2for more than 24 h impaired cell viability and proliferation. Hyperoxia did not significantly affect nitrotyrosine levels, nor eNOS mRNA and protein levels, regardless of the exposure time or oxygen concentration used. Phosphorylation of eNOS at the serine 1177 (S1177) residue and ET-1 mRNA levels were also not significantly affected.

CONCLUSIONS: Exposure of isolated human microvascular endothelial cells to marked hyperoxia for more than 24 h decreases cell viability and proliferation. Our results do not support a role of eNOS mRNA and protein or ET-1 mRNA in the potential vasoconstrictive effects of hyperoxia on isolated hMVEC.

Original languageEnglish
Article number22
JournalIntensive Care Medicine Experimental
Issue number1
Publication statusPublished - Apr 2017


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