Relative contribution of individual oxidized components in ox-LDL to inhibition on endothelium-dependent relaxation in rat aorta

Wong, W.T.; Ng, C.H.; Tsang, S.Y.; Huang, Y.; Chen, Z.-Y.

doi:10.1016/j.numecd.2008.12.017

« Previous Next »Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 3 , Pages 157-164, March 2011

Relative contribution of individual oxidized components in ox-LDL to inhibition on endothelium-dependent relaxation in rat aorta☆

W.T. Wong
- Institute of Vascular Medicine and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
C.H. Ng
- Food & Nutritional Sciences Programme of Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
S.Y. Tsang
- Food & Nutritional Sciences Programme of Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
Y. Huang
- Institute of Vascular Medicine and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
Z.-Y. Chen
- Institute of Vascular Medicine and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
- Food & Nutritional Sciences Programme of Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
- Corresponding author. Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. Tel.: +86 (852) 2609 6382; fax: +86 (852) 2603 7246.

Received 24 June 2008; received in revised form 3 October 2008; accepted 2 December 2008. published online 14 December 2009.

Abstract

Background and Aim

Oxidized low-density lipoprotein (ox-LDL) causes atherosclerosis and endothelial dysfunction. No study up to the present date has examined the relative contribution of all the oxidized components in ox-LDL to inhibition on vascular function. Our aim was to investigate the effects of individual oxidized components at concentrations similar to those in ox-LDL on the impairment of endothelium-dependent relaxation in rat aorta.

Methods and Results

Rat thoracic aorta was pre-treated with lysophosphatidylcholine (LPC), cholesterol oxidized products (COPs), oxidized linoleic acid (ox-18:2) and oxidized linolenic acid (ox-18:3) at concentrations similar to those in human ox-LDL. Ox-LDL as a whole caused 61% inhibition while LPC, COPs and ox-18:2 at concentrations similar to those in ox-LDL caused 12%, 24% and 19% inhibition, respectively, on endothelium-dependent relaxation, suggesting that COPs produced the most adverse effect followed by ox-18:2 and LPC in an additional way. Three COPs including 7-ketocholesterol, 7α-hydroxycholesterol and 7β-hydroxycholesterol showed inhibition on endothelium-dependent relaxation with E_max being reduced to 79–87% compared with the control E_max (95%). At Western blot analysis phosphorylation of eNOS at Ser1177 site and total eNOS were not altered by ox-LDL treatment, indicating that ox-LDL did not affect nitric oxide (NO) synthesis capacity. Ox-LDL might react directly with NO and lower NO bioavailability.

Conclusion

The present study demonstrated the relative contribution of individual oxidized components in ox-LDL in the inhibition of endothelium-dependent relaxation in rat aorta. This inhibitory effect could be caused by the reduction of NO bioactivity.

Keywords: Aorta, Cholesterol oxides, Lysophosphatidylcholine, Contraction, Ox-LDL