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


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.


CONCLUSIONS
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.
Wong
W T
WT
Institute of Vascular Medicine and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Ng
C H
CH
Tsang
S Y
SY
Huang
Y
Y
Chen
Z-Y
ZY
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis / Q000494:pharmacology; D066298:In Vitro Techniques; D007536:Isomerism; D007653:Ketocholesterols / Q000032:analysis / Q000494:pharmacology; D019787:Linoleic Acid / Q000737:chemistry / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000378:metabolism
D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein; D017962:alpha-Linolenic Acid; C011724:cholest-5-en-3 beta,7 alpha-diol; D002784:Cholesterol; D019787:Linoleic Acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C003001:7-ketocholesterol