Relative contribution of individual oxidized components in ox-LDL to inhibition on endothelium-dependent relaxation in rat aorta☆
Received 24 June 2008; received in revised form 3 October 2008; accepted 2 December 2008. published online 14 December 2009. Corrected Proof
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 Emax being reduced to 79–87% compared with the control Emax (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.
aInstitute of Vascular Medicine and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
bFood & 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.
☆ This project is supported by a grant (4586/06M) from the Hong Kong Research Grant Council and CUHK Focused Investment Scheme.
ABSTRACT