The effect of 7-ketocholesterol and 25-hydroxycholesterol on the integrity of the human aortic endothelial and intestinal epithelial barriersReportar como inadecuado

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Inflammation Research

, Volume 62, Issue 12, pp 1015–1023

First Online: 28 September 2013Received: 19 March 2013Accepted: 16 August 2013


Objective and designThe damage of barrtier tissues, such as the vascular endothelium and intestinal epithelium, may lead to disturbances of local immune homeostasis. The aim of the study was to assess and compare the effect of oxidized cholesterols 7-ketocholesterol and 25-hydroxycholesterol on the barrier properties of human primary aortic endothelium HAEC and intestinal epithelium Caco-2 cells using a real-time cell electric impedance sensing system RTCA-DP.

Materials and methodsHAEC and Caco-2 cells were stimulated with 7-ketocholesterol and 25-hydroxycholesterol by the RTCA-DP system. Apoptosis was assessed by flow cytometry and cell monolayer morphology was assessed under a light microscope.

Results7-ketocholesterol decreased impedance nCI in both the endothelium and epithelium. However, the decrease was more profound in the endothelium. Similarly, although 25-hydroxycholesterol decreased nCI in both the endothelium and epithelium, the effect was weaker than that of 7-ketocholesterol, which caused extensive damage to the endothelial monolayer, while 25-hydroxycholesterol caused partial damage and did not affect the epithelial monolayer. 7-ketocholesterol, but not 25-hydroxycholesterol, increased endothelial cell apoptosis and decreased the viability of endothelial cells. However, 7-ketocholesterol and 25-hydroxycholesterol decreased epithelial cell apoptosis and increased viability.

ConclusionOxidized cholesterols destroy the HAEC, but not the Caco-2 epithelial barrier, via cell apoptosis dependent on the site of oxidation. Damage to the endothelium by oxidized cholesterol may disrupt local homeostasis and provide open access to inner parts of the vascular wall for lipids, other peripheral blood-derived agents, and immune cells, leading to inflammation and atherogenesis.

KeywordsOxidized cholesterols Endothelium Intestinal epithelium Barrier functions Impedance Apoptosis Responsible Editor: Michael J. Parnham.

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Autor: Maciej Chalubinski - Katarzyna Zemanek - Wojciech Skowron - Katarzyna Wojdan - Paulina Gorzelak - Marlena Broncel


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