Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake

Helen R. Griffiths*, Sarah Aldred, Chloe Dale, Emi Nakano, George D. Kitas, Melissa G. Grant, Desmond Nugent, Fatai A. Taiwo, Li Li, Hilary J. Powers

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (<50 μM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy. © 2005 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)488-500
Number of pages13
JournalFree Radical Biology and Medicine
Volume40
Issue number3
Early online date11 Nov 2005
DOIs
Publication statusPublished - 1 Feb 2006

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Keywords

  • 3-Nitrotyrosine
  • cardiovascular disease
  • endothelial cell
  • free radicals
  • homocysteine
  • LDL
  • protein oxidation

Cite this

Griffiths, H. R., Aldred, S., Dale, C., Nakano, E., Kitas, G. D., Grant, M. G., Nugent, D., Taiwo, F. A., Li, L., & Powers, H. J. (2006). Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake. Free Radical Biology and Medicine, 40(3), 488-500. https://doi.org/10.1016/j.freeradbiomed.2005.08.039