Low density lipoprotein oxidized under lysosomal conditions decreases arterial vasodilatation

Alboaklah, H. K. M. ORCID: https://orcid.org/0000-0003-0272-5040, McNeish, A. J. ORCID: https://orcid.org/0000-0002-3466-8442 and Leake, D. S. ORCID: https://orcid.org/0000-0002-1742-6134 (2024) Low density lipoprotein oxidized under lysosomal conditions decreases arterial vasodilatation. Free Radical Research. ISSN 1029-2470 doi: 10.1080/10715762.2024.2403038

Abstract/Summary

Endothelial dysfunction is a risk factor for atherosclerosis and includes impaired endothelium-dependent vasodilatation. We have shown previously that low density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Macrophage lysis in atherosclerotic lesions might expose endothelial cells to this oxidized LDL and adversely affect their function. LDL was oxidized by ferrous sulfate (5 µM) for 24 h at pH 4.5 at 37 °C. Aortas from male Wistar rats were cut into rings and subjected to wire myography for isometric tension recording. The rings were incubated with or without oxidized LDL (50 µg protein/ml) for one hour, constricted with 100 nM phenylephrine and relaxation to acetylcholine (1 nM − 3 µM) was measured. There was about 50% less relaxation in the presence of this oxidized LDL. Endothelial-independent vasodilatation induced by sodium nitroprusside was less affected by oxidized LDL. Oxidized LDL increased the formation of reactive oxygen species by the aortic rings and by cultured human aortic and dermal microvascular endothelial cells, which might have inactivated nitric oxide. Acetylcholine increased the activatory phosphorylation of eNOS (ser-1177), but oxidized LDL had little effect on this activation in cultured human aortic endothelial cells. These findings raise the possibility that LDL oxidized in lysosomes and released from lysed macrophages might decrease vasodilatation in atherosclerotic arteries.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/118582
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Taylor and Francis
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