Presence of hypochlorite-modified proteins in human atherosclerotic lesions.

Abstract

Oxidation of LDL may contribute to atherogenesis, though the nature of the in vivo oxidant(s) remains obscure. Myeloperoxidase, the enzyme responsible for hypochlorous acid/hypochlorite (HOCl) production in vivo, is present in active form in human atherosclerotic lesions, and HOCl aggregates and transforms LDL into a high-uptake form for macrophages in vitro. Here we demonstrate HOCl-modified proteins in human lesions using an mAb raised against HOCl-modified LDL that recognizes HOCl-oxidized proteins but does not cross-react with Cu

Biochemistry and pathology of radical-mediated protein oxidation

“…[261]). Studies on hypochlorite-oxidized protein, in which antisera specificities have been carefully validated, suggest not only that hypochlorite-oxidized proteins are present in plaques, but also that apoB peptides are among them [262]. HOCl appears to attack the protein selectively [97,263].…”

Chlorotyrosine promotes human aortic smooth muscle cell migration through increasing superoxide anion production and ERK1/2 activation

“…It catalyzes the two-electron peroxidation of chloride to generate hypochlorous acid (HOCl) [2], a potent chlorinating oxidant, capable of chlorinating tyrosine into chlorotyrosine. Levels of chlorotyrosine are increased in atherosclerotic tissues [3] and the blood of in patients with inflammatory conditions including atherosclerosis [4,25,26]. The chlorination of apolipoprotein A-I was found to impair its cardioprotective ability to remove excess cellular cholesterol from lipid-laden macrophages in the artery wall [5].…”

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

“…Evidence has been obtained for the modification of ECM components by MPO-derived oxidants in human atherosclerotic lesions by use of a monoclonal antibody (HOP-1) raised against HOCldamaged LDLs. This antibody does not recognize proteins oxidized by a wide variety of other oxidants in itro [39]. Application of this antibody resulted in significant staining of both intra-and extra-cellular locations, particularly in the intimal area and at cholesterol clefts, with little staining detected in normal human artery samples [39].…”

“…This antibody does not recognize proteins oxidized by a wide variety of other oxidants in itro [39]. Application of this antibody resulted in significant staining of both intra-and extra-cellular locations, particularly in the intimal area and at cholesterol clefts, with little staining detected in normal human artery samples [39]. Recent studies have demonstrated that the intensity of staining induced by this antibody correlates with intimal thickening in lesions of differing severity, suggesting that the MPO-induced damage plays a role in lesion development [40].…”