High-Density Lipoprotein from Hypercholesterolemic Animals Has Peroxidized Lipids and Oligomeric Apolipoprotein A-I: Its Putative Role in Atherogenesis

Artola, Rodolfo L.; Conde, Cecı́lia; Bagatolli, Luís A.; Pécora, Rolando Pascual; Fidelio, Gerardo D.; Kivatinitz, Silvia C.

doi:10.1006/bbrc.1997.7496

Cited by 19 publications

(16 citation statements)

References 24 publications

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“…Thus, apoA-I represents a selective target for chlorination and nitration in human atheromatous tissue catalyzed by myeloperoxidase. In vivo oxidation of apoA-I is equally consistent with the observation that HDL from hypercholesterolemic chickens contain higher amounts of oligomeric apoA-I and are more susceptible to in vitro oxidation than HDL from control animals (Artola et al, 1997).…”

Section: A Altered High-density Lipoprotein Composition and Enzymatisupporting

confidence: 83%

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Kontush¹,

Chapman²

2006

Pharmacol Rev

654

594

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Section: A Altered High-density Lipoprotein Composition and Enzymatisupporting

confidence: 83%

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Kontush¹,

Chapman²

2006

Pharmacol Rev

654

594

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“…Though we cannot explain the mechanism why the absence of HO-1 resulted in the compositional change of HDL and produced oxidized HDL, it may be possible to understand HO-1 functions to prevent HDL particle and apolipoproteins from oxidative stress. It is reported that apolipoprotein AI starts denaturation and is easy to make oligomers in oxidized HDL [30]. However, in this study, we did not find oligomeric bands.…”

Section: Resultscontrasting

confidence: 88%

Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice

Ishikawa

Navab

Lusis

2012

International Journal of Hypertension

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To elucidate roles of heme oxygenase-1 (HO-1) in cardiovascular system, we have analyzed one-year-old HO-1-knockout mice. Homozygous HO-1-knockout mice had severe aortitis and coronary arteritis with mononuclear cellular infiltration and fatty streak formation even on a standard chow diet. Levels of plasma total cholesterol and HDL were similar among the three genotypes. However, homozygous HO-1-knockout mice had lower body weight and plasma triglyceride. HO-1-deficiency resulted in alteration of the composition of HDL. The ratio of apolipoprotein AI to AII in HO-1-knockout mice was reduced about 10-fold as compared to wild-type mice. In addition, paraoxonase, an enzyme against oxidative stress, was reduced less than 50% in HO-1-knockout mice. The knockout mice also exhibited significant elevation of plasma lipid hydroperoxides. This study using aged HO-1-knockout mice strengthened the idea that HO-1 functions to suppress systemic inflammation in artery wall and prevents plasma lipid peroxidation.

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“…In fact, cross-linking of lipid-bound apoA-I reduces its helical content (Fig. 4) and reportedly increases solvent exposure of specific protein α-helices (16,33,34), which may weaken protein-lipid interactions and promote protein dissociation and lipoprotein remodeling and fusion.…”

Section: Discussionmentioning

confidence: 99%

Effects of Protein Oxidation on the Structure and Stability of Model Discoidal High-Density Lipoproteins

2008

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High-density lipoproteins (HDLs) prevent atherosclerosis by removing cholesterol from macrophages and by providing anti-oxidants for low-density lipoproteins. Oxidation of HDLs affects their functions via the complex mechanisms that involve multiple protein and lipid modifications. To differentiate between the roles of oxidative modifications in HDL proteins and lipids, we analyzed the effects of selective protein oxidation by hypochlorite (HOCl) on the structure, stability and remodeling of discoidal HDLs reconstituted from human apolipoproteins (A-I, A-II or C-I) and phosphatidylcholines. Gel electrophoresis and electron microscopy revealed that, at ambient temperatures, protein oxidation in discoidal complexes promotes their remodeling into larger and smaller particles. Thermal denaturation monitored by far-UV circular dichroism and light scattering in melting and kinetic experiments shows that protein oxidation destabilizes discoidal lipoproteins and accelerates protein unfolding, dissociation and lipoprotein fusion. This is likely due to reduced protein affinity for lipid resulting from oxidation of Met and aromatic residues in the lipid-binding faces of amphipathic α-helices and to apolipoprotein cross-linking into dimers and trimers on the particle surface. We conclude that protein oxidation destabilizes HDL disk assembly and accelerates its remodeling and fusion. This result, which is not limited to model discoidal but also extends to plasma spherical HDL, helps explain the complex effects of oxidation on plasma lipoproteins. KeywordsThermal stability; lipoprotein remodeling and fusion; apolipoprotein A-I; reverse cholesterol transport; atherosclerosis High-density lipoproteins (HDLs) remove excess cholesterol from the body and thereby prevent atherosclerosis. Plasma HDLs form a heterogeneous population of particles differing in their protein and lipid composition, shape, size, and functional properties. Nascent discoidal HDLs are comprised of a cholesterol-containing phospholipid bilayer and apolipoproteins wrapped around the particle perimeter in a beltlike amphipathic α-helical conformation (1). Mature spherical HDLs contain proteins, phospholipids and free (unesterified) cholesterol (FC) in their surface and apolar lipids (mainly cholesterol esters) in the core (2).Apolipoprotein A-I (apoA-I, 28 kDa) is a key structural and functional component of HDL that comprises ∼70 % of the total HDL protein content. Plasma levels of HDL and apoA-I are inversely related to the risk of atherosclerosis (3). HDLs protect against atherosclerosis by removing excess cholesterol from arterial macrophages and other peripheral cells via the reverse cholesterol transport (RCT) pathway (2). Other cardioprotective mechanisms have been proposed to involve the antioxidant and antiinflammatory properties of HDL and its NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript constituent proteins, including apoA-I (4-10). ApoA-I also plays key roles at various stages of RCT. It promotes efflux of cell ...

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High-Density Lipoprotein from Hypercholesterolemic Animals Has Peroxidized Lipids and Oligomeric Apolipoprotein A-I: Its Putative Role in Atherogenesis

Cited by 19 publications

References 24 publications

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice

Effects of Protein Oxidation on the Structure and Stability of Model Discoidal High-Density Lipoproteins

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