2-Chlorohexadecanal Derived From Hypochlorite-Modified High-Density Lipoprotein–Associated Plasmalogen Is a Natural Inhibitor of Endothelial Nitric Oxide Biosynthesis

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 12; pp. 2302 - 2306
• Main Authors: Marsche, Gunther, Heller, Regine, Fauler, Günter, Kovacevic, Alenka, Nuszkowski, Alexander, Graier, Wolfgang, Sattler, Wolfgang, Malle, Ernst
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2004; Hagerstown, MD Lippincott
• Subjects: Aldehydes - metabolism; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Line; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - enzymology; Endothelial Cells - metabolism; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Enzyme Activation - drug effects; Enzyme Activation - physiology; Heart; Humans; Hypochlorous Acid - metabolism; Lipoproteins, HDL - metabolism; Medical sciences; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type III; Plasmalogens - metabolism; Umbilical Veins - cytology; Umbilical Veins - enzymology; Umbilical Veins - metabolism; glomerulosclerosis; Enzyme; Cardiovascular disease; Biosynthesis; myeloperoxidase; 2-chlorinated fatty aldehyde; Aldehyde; Lipoprotein a; Vascular disease; Peroxidases; Nitric oxide; Atherosclerosis; modified lipids; Peroxidase; Oxidoreductases; Neutrophil; neutrophils
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000148703.43429.25

OBJECTIVE—Myeloperoxidase, a heme enzyme that is present and active in human atherosclerotic lesions, provides a source for the generation of proinflammatory chlorinated reactants contributing to endothelial dysfunction. Modification of high-density lipoprotein (HDL) by hypochlorous acid/hypochlorite (HOCl/Oce)—generated in vivo by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes—forms a proatherogenic lipoprotein particle that binds to and is internalized by endothelial cells. METHODS AND RESULTS—Here we show that HDL, modified with physiologically relevant HOCl concentrations, attenuates the expression and activity of vasculoprotective endothelial nitric oxide synthase. HOCl-HDL promotes dislocalization of endothelial nitric oxide synthase from the plasma membrane and perinuclear location of human umbilical venous endothelial cells. We could identify 2-chlorohexadecanal as the active component mediating this inhibitory activity. This chlorinated fatty aldehyde is formed during HOCl-mediated oxidative cleavage of HDL-associated plasmalogen. CONCLUSION—2-Chlorohexadecanal, produced by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes may act as a mediator of vascular injury associated with ischemia-reperfusion injury, glomerulosclerosis, and atherosclerosis.