Mechanisms of Atherosclerosis: Role of LDL Oxidation

Author(s):  
Peter D. Reaven
Keyword(s):  
2000 ◽  
pp. 79-83 ◽  
Author(s):  
W Abplanalp ◽  
MD Scheiber ◽  
K Moon ◽  
B Kessel ◽  
JH Liu ◽  
...  

Estrogens possess strong antioxidant effects in vitro, but in vivo studies in humans have yielded conflicting results. Little is known regarding factors that mediate the antioxidant effect of estrogens in vivo. In this study the potential role of high density lipoprotein (HDL) was examined. The antioxidant effect of estradiol-17beta (E2) added to low density lipoprotein (LDL) was lost after dialysis. In contrast, the antioxidant effect of E2 added to HDL was conserved after dialysis, suggesting that E2 was bound to HDL. Binding of E2 to LDL increased after esterification (especially to long chain fatty acids). In the presence of HDL, an increased amount of E2 was transferred to LDL. E2-17 ester was as potent as E2 in preventing LDL oxidation in vitro, but 3,17-diesters were not as effective (E2=E2-17 ester>E2-3 ester>E2-3,17 diester). This was also supported by experiments which showed that estrogens with masked 3-OH groups were not effective as antioxidants. These studies provide evidence that HDL could facilitate the antioxidant effect of E2 through initial association, esterification and eventual transfer of E2 esters to LDL. Therefore it is critical that HDL peroxidation parameters be evaluated in subjects receiving estrogen replacement therapy.


2003 ◽  
Vol 4 (2) ◽  
pp. 120
Author(s):  
E. Nakano ◽  
D. Nugent ◽  
F. Taiwo ◽  
H. Powers

2009 ◽  
Vol 102 (6) ◽  
pp. 793-796 ◽  
Author(s):  
Corinna E. Rüfer ◽  
Sabine E. Kulling ◽  
Jutta Möseneder ◽  
Peter Winterhalter ◽  
Achim Bub

Isoflavone intake is associated with various properties beneficial to human health which are related to their antioxidant activity, for example, to their ability to increase LDL oxidation resistance. However, the distribution of isoflavones among plasma lipoproteins has not yet been elucidated in vivo. Therefore, the objective of the present study was to investigate the association between daidzein (DAI) and lipoproteins in human plasma upon administration of the aglycone and glucoside form. Five men aged 22–30 years participated in a randomised, double-blind study in cross-over design. After ingestion of DAI and daidzein-7-O-β-d-glucoside (DG) (1 mg DAI aglycone equivalents/kg body weight) blood samples were drawn before isoflavone administration as well as 1, 2, 3, 4·5, 6, 8, 10, 12, 24 and 48 h post-dose. Concentrations of DAI in the different lipoprotein fractions (chylomicrons, VLDL, LDL, HDL) and in the non-lipoprotein fraction were analysed using isotope dilution capillary GC/MS. The lipoprotein fraction profiles were similar for all subjects and resembled those obtained for plasma in our previously published study. The lipoprotein distribution based on the area under the concentration–time profiles from 0 h to infinity in the different fractions were irrespective of the administered form: non-lipoprotein fraction (53 %) > LDL (20 %) > HDL (14 %) > VLDL (9·5 %) > chylomicrons (2·5 %). Of DAI present in plasma, 47 % was associated to lipoproteins. Concentrations in the different lipoprotein fractions as well as in the non-lipoprotein fraction were always higher after the ingestion of DG than of DAI. Taken together, these results demonstrate an association between isoflavones and plasma lipoproteins in vivo.


2007 ◽  
Vol 53 (8) ◽  
pp. 1397-1400 ◽  
Author(s):  
Joris R Delanghe ◽  
Michel R Langlois ◽  
Marc L De Buyzere ◽  
Mathieu A Torck

Abstract Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype–related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.


2009 ◽  
Vol 5 (2) ◽  
pp. 86
Author(s):  
Andrew Carson ◽  

Atherosclerotic disease has been a feature of more affluent societies since ancient times. Currently, cardiovascular disease accounts for almost half of all mortality across Europe, causing over two million deaths within the EU and costing EU health economies €192 billion per year. The pathogenesis of atherosclerosis is complex, and our understanding of it has come a long way over the last 50 years. The public and many health professionals have an image of cholesterol that is probably over-simplistic. The oxidation of lowdensity lipoprotein (LDL) cholesterol to form oxLDL is the first molecular step in atherosclerosis pathogenesis, and it appears that oxLDL levels may act as a useful biomarker in identifying individuals at greatest risk of cardiovascular events. Inhibition of oxLDL or its active removal may represent a useful new therapeutic strategy. Antioxidants such as lycopene may offer another approach to prevention or treatment, and emerging evidence around the role of anti-Chlamydia pneumoniae antibodies in LDL oxidation could open up another avenue of preventative and therapeutic options.


2011 ◽  
pp. P1-664-P1-664
Author(s):  
Roberto Vicinanza ◽  
Giuseppe Coppotelli ◽  
Carolina Malacrino ◽  
Tiziana Nardo ◽  
Barbara Buchetti ◽  
...  

1999 ◽  
Vol 40 (7) ◽  
pp. 1347-1356
Author(s):  
Chavali Balagopalakrishna ◽  
Latha Paka ◽  
Sivaram Pillarisetti ◽  
Ira J. Goldberg

2005 ◽  
Vol 35 (3) ◽  
pp. 531-545 ◽  
Author(s):  
B Löhrke ◽  
T Viergutz ◽  
B Krüger

The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5–11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3β-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17β-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.


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