This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Volf, I. Articles by Koller, E. Search for Related Content PubMed PubMed Citation Articles by Volf, I. Articles by Koller, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 2,6-DI-T-BUTYL-P-CRESOL CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Oxidant stress Platelets Pathophysiology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2011.)
© 2000 American Heart Association, Inc.

Thrombosis

Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist

Presented in part at the 17th International Congress of Biochemistry and Molecular Biology, San Francisco, Calif, 1997, and at the XIII Symposium on Platelets, Schloss Seggau, Austria, 1998.

Ivo Volf; Edith Bielek; Thomas Moeslinger; Franz Koller; Elisabeth Koller

From the Institute of Physiology (I.V., T.M., E.K.), the Institute of Histology and Embryology (E.B.), and the Institute of Biochemistry and Cell Biology (F.K.), University of Vienna, Vienna, Austria.

Correspondence to Dr Elisabeth Koller, Institute of Medical Physiology, University of Vienna, Schwarzspanierstr. 17, A-1090 Vienna, Austria. E-mail elisabeth.koller{at}univie.ac.at

Abstract—Conflicting reports exist about the effects of mildly or extensively oxidized low density lipoproteins (LDLs) on the reactivity of human platelets. This platelet response is mainly caused by modification of the protein and lipid moiety, giving rise to very differently modified species with hardly predictable properties. The aim of this study was to prepare oxidized LDL with modifications essentially restricted to the protein moiety and to determine the eventual platelet responses. We treated LDL at 0°C for 10 minutes with a 60- to 1000-fold molar excess of sodium hypochlorite in borate buffer in the presence of the radical scavenger butylated hydroxytoluene. Under these conditions, neither fragmentation of apolipoprotein B-100 nor formation of LDL aggregates was observed, and lipid oxidation products did not exceed the amount present in untreated LDLs. The degree of modification and the respective effects on platelet function were highly reproducible. Hypochlorite-modified LDLs act as strong platelet agonists, inducing morphological changes, dense granule release, and irreversible platelet aggregation. The evoked platelet effects are completely suppressed by inhibitors of the phosphoinositide cycle but not by EDTA or acetylsalicylic acid. Most likely, these effects are transmitted via high-affinity binding to a single class of sites, which does not recognize native or acetylated LDL. Obviously, modified lysines, and the secondary lipid modifications derived from them, are not essential for this interaction. We conclude that bioactive oxidized lipids are not directly involved in the stimulation of platelets by hypochlorite-modified LDLs.

Key Words: atherosclerosis • oxidized LDL • apoB-100 • human platelets • platelet aggregation

This article has been cited by other articles:

				L. G. Coleman Jr, R. K. Polanowska-Grabowska, M. Marcinkiewicz, and A. R. L. Gear LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22) Blood, July 15, 2004; 104(2): 380 - 389. [Abstract] [Full Text] [PDF]