Myeloperoxidase‐induced lipid peroxidation of LDL in the presence of nitrite. Protection by cocoa flavanols

Abstract

Lipid peroxidation (LPO) of low-density lipoprotein (LDL) is believed to be a pivotal process rendering this plasma lipoprotein atherogenic. Several endogenous factors have been proposed to mediate LPO of LDL, among them myeloperoxidase (MPO), which is active in atherosclerotic lesions, and the plasma level of which has been proposed to be a prognostic parameter for cardiac events. Nitrite, a major oxidation product of nitric oxide, is substrate of MPO and a cofactor of MPO-mediated LPO under physiological conditions. Dietary flavonoids including (-)-epicatechin, a major flavan-3-ol in cocoa products, grapes and wine, are substrates of MPO as well as potent inhibitors of LPO in LDL at micromolar concentrations. Moreover, they strongly suppress protein tyrosine nitration of LDL by MPO/nitrite or peroxynitrite. By blunting undesirable MPO-mediated actions of nitrite, presumably via scavenging of the strong prooxidant and nitrating *NO2 radical, dietary flavonoids modulate NO metabolism in a favorable direction and thus counteract endothelial dysfunction. This article gives a survey on recent progress in this field with special reference to own recently published work.

Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet

“…MPO and oxLDL are molecules involved in the development of oxidative stress and consequently in atherosclerosis (22)(23). Particles of oxLDL are generated during lipid peroxidation, and are able to damage endothelial cells.…”

Myeloperoxidase-mediated LDL oxidation and endothelial cell toxicity of oxidized LDL: attenuation by (−)-epicatechin

“…We have demonstrated that (2 )-epicatechin and other flavonoids protect LDL against oxidation by either MPO/H 2 O 2 /nitrite reaction system or Cu 2 þ catalysis [23,27,28]. Moreover, (2 )-epicatechin protects endothelial cells against both cytotoxicity of oxLDL and oxLDL-mediated proteasomal degradation of endothelial z NO synthase protein [29].…”

“…In a recent review, we have treated the enzymatic properties of myeloperoxidase (MPO) with emphasis on its reactions with nitrite, flavonoids and LDL and their putative biological role in atherogenesis [23]. Main focus of present review is recent work from this laboratory on the cytotoxic action of oxLDL, generated by the MPO/H 2 O 2 /nitrite reaction system, on vascular endothelial cells and its possible role in endothelial dysfunction as well as protective actions of various vasoprotective agents.…”

Nitrite, a naturally occurring precursor of nitric oxide that acts like a ‘prodrug’

“…In the inflamed subendothelial space, myeloperoxidase is released from activated neutrophils and is capable of inducing lipid peroxidation of low-density lipoprotein at moderate nitrite concentrations (5-50 mM), which may be an initial step in atherogenesis (for a review, see Schewe and Sies, 2005 …”