Effects of Chronic Apolipoprotein E Deficiency on Mouse Ophthalmic Artery Reactivity

Francesco Buonfiglio; Ning Xia; Can Yüksel; Caroline Manicam; Subao Jiang; Jenia Kouchek Zadeh; Aytan Musayeva; Eva Elksne; Norbert Pfeiffer; Andreas Patzak; Huige Li; Adrian Gericke

doi:10.20944/preprints202308.1630.v1

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preprints.org > medicine and pharmacology > ophthalmology > doi: 10.20944/preprints202308.1630.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of Chronic Apolipoprotein E Deficiency on Mouse Ophthalmic Artery Reactivity

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Version 1 : Received: 18 August 2023 / Approved: 22 August 2023 / Online: 23 August 2023 (07:35:16 CEST)

A peer-reviewed article of this Preprint also exists.

Buonfiglio, F.; Xia, N.; Yüksel, C.; Manicam, C.; Jiang, S.; Zadeh, J.K.; Musayeva, A.; Elksne, E.; Pfeiffer, N.; Patzak, A.; Li, H.; Gericke, A. Studies on the Effects of Hypercholesterolemia on Mouse Ophthalmic Artery Reactivity. Diseases 2023, 11, 124. Buonfiglio, F.; Xia, N.; Yüksel, C.; Manicam, C.; Jiang, S.; Zadeh, J.K.; Musayeva, A.; Elksne, E.; Pfeiffer, N.; Patzak, A.; Li, H.; Gericke, A. Studies on the Effects of Hypercholesterolemia on Mouse Ophthalmic Artery Reactivity. Diseases 2023, 11, 124.

Abstract

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, vascular mechanics, lipid content, levels of reactive oxygen species (ROS), expression of pro-oxidant redox enzymes and of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and of LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via involvement of LOX-1, NOX1 and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. Lack of LOX-1 expression/overexpression in response to increased ox-LDL levels may be a possible mechanism of action.

Keywords

aorta; apolipoprotein E; hypercholesterolemia; ophthalmic artery; oxidative stress

Subject

Medicine and Pharmacology, Ophthalmology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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