Hypochlorite induces the formation of LDL⁻, a potentially atherogenic low density lipoprotein subspecies

Abstract

Oxidation of low density lipoprotein (LDL) induced by hypochlorous acid (HOCl) leading to LDL 3 , a minimally oxidized subspecies of LDL, was investigated. LDL 3 is characterized by its greater electronegativity and oxidative status, and is found in plasma in vivo. Its concentration was found to be elevated under conditions that predispose humans to atherosclerosis. We found that HOCl also converts LDL rapidly to an even more oxidized state, identified as LDL 23 , which is more electronegative than LDL 3 . After milder oxidation for short durations, formation of LDL 3 takes place while less LDL 23 is formed. Under these conditions, addition of methionine not only suppressed further oxidation of LDL but also favored the formation of LDL 3 over LDL 23 , possibly by removing chloramines at lysyl residues of LDL. The presence of lipoprotein-deficient plasma did not prevent HOCl-mediated conversion of LDL to more electronegative species. It is concluded that the HOCl-mediated conversion of LDL into more electronegative species might be physiologically relevant. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Potential to inhibit growth of atherosclerotic plaque development through modulation of macrophage neopterin/7,8‐dihydroneopterin synthesis

“…Hypochlorite is released from activated neutrophils and possibly macrophages during inflammation ( Chisolm et al , 1999 ). This highly reactive oxidant has been implicated in the modification of LDL within plaques and killing cells ( Daugherty et al , 1994 ; Fabjan et al , 2001 ; Whiteman et al , 2005 ). 7,8‐Dihydroneopterin protects cells from hypochlorite by rapidly reacting with it ( Gieseg et al , 2001a , 2001b ).…”

Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression

“…9,10 However, LDL 2Ϫ , which harbors a more electronegative charge than LDL Ϫ , constitutes 0.1% to 1% of total LDL and seems to be a more oxidized subfraction of LDL. 11 A recent report has elaborated the characteristics of modified LDL species based on electronegative charge and their oxidation characteristics. 12 Three possible sources proposed for LDL Ϫ are the following: (1) oxidation of LDL entrapped in the arterial wall, 13 (2) ingestion of oxidants or generation from postprandial lipoprotein remnants, 14 and (3) oxidation in plasma.…”

LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein

“…There are several mechanisms described for LDL Ϫ formation, each yielding a particle resembling circulating LDL Ϫ . Particles similar to LDL Ϫ can be produced in vitro by transition metals or hemoproteins (6,10), enzymatically by myeloperoxidase (12), lipoxygenase, and lipase (13,14), and by incubating LDL in the presence of vascular cells (15), particularly under shear stress (16). All of these reactions occur with concomitant lipid peroxidation in LDL particles with levels at times greatly exceeding those found in plasma LDL Ϫ .…”