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Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 1995 Sep;77(3):510-8

Date

09/01/1995

Pubmed ID

7543827

DOI

10.1161/01.res.77.3.510

Scopus ID

2-s2.0-0029133481   436 Citations

Abstract

To examine mechanisms by which native low-density lipoprotein (n-LDL) perturbs endothelial cell (EC) release of superoxide anion (O2-) and nitric oxide (NO), ECs were incubated with n-LDL at 240 mg cholesterol per deciliter for 4 days with media changes every 24 hours. n-LDL increases EC release of O2- by more than fourfold and increases nitrite production by 57%. In the conditioned media from day-4 incubations, n-LDL increases total nitrogen oxides 20 times control EC (C-EC) levels. However, n-LDL did not alter EC NO synthase (eNOS) enzyme activity as measured by the [3H]citrulline assay. N omega-Nitro-L-arginine methyl ester, a specific inhibitor of eNOS activity, increases C-EC release of O2- by > 300% but decreases LDL-treated EC (LDL-EC) release by > 95%. L-Arginine inhibits the release of O2- from LDL-ECs by > 95% but did not effect C-EC release of O2-. Indomethacin and SKF 525A partially attenuate LDL-induced increases in O2- production by approximately 50% and 30%, respectively. Thus, n-LDL increases O2- and NO production, which increases the likelihood of the formation of peroxynitrite (ONOO-), a potent oxidant. n-LDL increases the levels of nitrotyrosine, a stable oxidation product of ONOO-, and tyrosine by approximately 50%. In spite of this increase in oxidative metabolism, analysis of thiobarbituric acid substances reveals that no significant changes in the oxidation of n-LDL occur during the 24-hour incubations with ECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Pritchard KA Jr, Groszek L, Smalley DM, Sessa WC, Wu M, Villalon P, Wolin MS, Stemerman MB

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Oxidoreductases
Arginine
Cells, Cultured
Endothelium, Vascular
Humans
Lipoproteins, LDL
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Superoxides
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a