Regression of atherosclerosis in rabbits

Vesselinovitch, Dragoslava; Wissler, Robert W.; Fisher-Dzoga, Katti; Hughes, Randolph; DuBien, L.H.

doi:10.1016/0021-9150(74)90061-6

Cited by 88 publications

(1 citation statement)

References 26 publications

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“…In addition, diverse treatments that are expected to increase the potential for oxidation in blood decrease cholesterol levels in serum. Thus, the pro-oxidant effect of increased dietary polyunsaturated fats (37)(38)(39), intramuscular injection of peroxidase (40), increased oxygen respiration (41)(42)(43), and whole-body ultraviolet irradiation (44,45) decreased serum cholesterol levels. In contrast, the expected anti-oxidant effect of increased dietary saturated fats (38,39,46), decreased oxygen respiration (47,48), cigarette smoking (49), increased carbon monoxide respiration (50,51), dietary vitamin E (52-54), and dietary butylated hydroxytoluene (55) resulted in increased levels of serum cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Schuh¹,

Fairclough²,

Haschemeyer³

1978

Proc. Natl. Acad. Sci. U.S.A.

245

121

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Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower mo ecular weight polypeptide components, as characterized by sodium dodecyl sulfate/ polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions. Structural and functional characterization of serum lipoproteins has received attention because molecular or metabolic abnormalities associated with this class of molecules might be significant in the development of atherosclerosis (1). The lowdensity lipoprotein fraction (LDL) has been of particular interest because of its apparent role in atherogenesis. Such a role is indicated by a correlation between high serum levels of LDL and clinical atherosclerosis (2), as well as the accelerated atherosclerosis in patients who have an inherited abnormality in LDL catabolism (familial hypercholesterolemia) (3). LDL is catabolized after it is bound through its protein moiety (apo-B or apo-LDL) to a cell-surface receptor (4).Although characterization of the apoprotein of LDL has been difficult (5), studies on the lipid moiety appear to be less controversial. LDL contains a large proportion of unsaturated lipids (somewhat variable on diet) (6) and is unique among the serum lipoproteins in its susceptibility for undergoing auto-oxidation in vitro (7-9). This finding has led some authors to speculate that such auto-oxidation plays a role in atherogenesis (7,10,11). Although structural (7-13), spectrophotometric (9,13,14), and lipid compositional (8, 11) changes in LDL have been observed upon oxidation, its polypeptide chain has not been characterized. Model studies with lipid-protein mixtures have shown that oxidized lipid can lead to major modification of protein components; such modifications include crosslinking (15), polypeptide scission (16), and loss of amino acids (17, 18). It thus seems possible that some of the difficulties encountered in characterizing apo-B are associated with partial oxidation of LDL during purification and/or storage. The observation that plasma lipids from human subjects contain significant diene conjugation (an early manifestation of lipid auto-oxidation) suggests that oxidation of LDL can be initiated in vivo (19).We show here that mild oxidation of LDL in vitro results in altering the sodium dodecyl sulfate (NaDodSO4)-apoprotein electrophoretic pattern from a single major band of low mobility into nume...

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