Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis

1991 ◽  
Vol 89 (2-3) ◽  
pp. 117-126 ◽  
Author(s):  
Howard N. Hodis ◽  
Donald W. Crawford ◽  
Alex Sevanian
1979 ◽  
Vol 57 (11) ◽  
pp. 1273-1280 ◽  
Author(s):  
F. W. Keeley

The synthesis of soluble elastin, newly synthesized insoluble elastin and total accumulated insoluble elastin was measured in aortic tissue of chickens ranging in age from the 11-day embryo to the adult chicken. Synthesis of soluble elastin reached a maximum in the 1st week after hatching, then decreased rapidly with a second transient increase between 4 and 6 weeks and thereafter decreased continuously until synthesis could no longer be detected in the 35-week-old adult. A portion of this newly synthesized soluble elastin was insolubilized even during 1 h of incubation by a β-aminopropionitrile-inhibited mechanism. Total insoluble elastin accumulated rapidly in aortic tissue in the late embryonic stages and reached a plateau about 1 week after hatching, after which time the proportion of the protein in the tissue remained constant. Synthesis of soluble elastin and total insoluble elastin was also determined in aortic tissue of chickens raised on a diet containing 2% cholesterol for 14 weeks after hatching. This cholesterol-rich diet had an early, but transient effect on the synthesis of soluble elastin, shifting the age of maximal synthesis to 1 to 2 weeks after hatching. However, by 6 to 8 weeks on the diet there was no difference in soluble elastin synthesis between normal and cholesterol-fed groups. Although prolonged cholesterol feeding resulted in serum cholesterol levels 10 times normal, aortic tissue cholesterol levels 3 times normal and grossly visible atherosclerotic lesions, no reinitiation of soluble elastin synthesis or alteration in the quantity and character of insoluble aortic elastin could be detected.


2014 ◽  
Vol 38 (1) ◽  
pp. 62-70
Author(s):  
Baraa Najim Al-Okaily

This experiment was aimed to investigate the role of pomegranate seed oil (PSO) in ameliorating the deleterious effects of methionine overload on some histopathological structure of heart and aorta in adult female rabbits. Thirty-Two female rabbits divided into four groups eight animals each, and treated for 42 days daily as follows: the first groups were drenched drinking corn oil, serving as control (group C), second group (group T1) were intubated orally with methionine 100mg/kg. B.W, while the third group (groupT2) were intubated orally with methionine 100mg/kg. B.W and pomegranate seed oil (PSO) 30 mg /Kg. B.W, and the animals in group T3 were intubated orally with pomegranate seed oil 30 mg /Kg. B.W. At the end of the experiment rabbits were sacrificed. Serial sections from the heart and aorta were prepared and examined microscopically. Histological examination of heart and aorta of methionine overload treated group (T1) showed edema ,RBCs and few neutrophils infiltration ,with vacuolar degeneration of cardiac muscle cells , fragment of muscle fiber, congested blood vessels between muscle fibers. An increase in thickness of intima, erosion and mononuclear cells infiltration in sub intima of aorta were also observed. Histological sections of heart and aorta in T2 and T3 groups showed the absence of histopathological lesions in aortic tissue with moderate edema between muscle fiber of T2 group as comparing to group T1. In conclusion, the results confirm the cardioprotective role of pomegranate seed oil by ameliorating the effect of methionine overload on cardiac muscle and aorta.


2020 ◽  
Vol 40 (9) ◽  
pp. 2070-2083
Author(s):  
Lin-Lin Wei ◽  
Ning Ma ◽  
Kun-Yi Wu ◽  
Jia-Xing Wang ◽  
Teng-Yue Diao ◽  
...  

Objective: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar −/− /Apoe −/− mice were generated by cross-breeding of atherosclerosis-prone Apoe −/− mice and C3ar −/− mice. C3ar −/− /Apoe −/− mice and Apoe −/− mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b + leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe −/− mice, C3ar −/− /Apoe −/− mice developed more severe atherosclerosis. In addition, C3ar −/− /Apoe −/− mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. Conclusions: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis–mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.


2008 ◽  
Vol 80 (8) ◽  
pp. 1849-1858 ◽  
Author(s):  
Paul Wentworth ◽  
Daniel P. Witter

The intrinsic ability of all antibodies to generate hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) via the antibody-catalyzed water-oxidation pathway (ACWOP) has triggered a rethink of the potential role of antibodies both in immune defense, inflammation, and disease. It has been shown that photochemical activation of this pathway is highly bactericidal. More recently, cholesterol oxidation by-products that may arise from the ACWOP have been discovered in vivo and are receiving a great deal of attention as possible key players in atherosclerosis and diseases of protein misfolding, such as Alzheimer's disease and Parkinson's disease.


2002 ◽  
Vol 162 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Kaixun Huang ◽  
Hongmei Liu ◽  
Zexian Chen ◽  
Huibi Xu

2003 ◽  
Vol 36 (3-4) ◽  
Author(s):  
ALFONSO VALENZUELA ◽  
JULIO SANHUEZA ◽  
SUSANA NIETO

1998 ◽  
Vol 80 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Yvonne V. Yuan ◽  
David D. Kitts ◽  
David V. Godin

Increasing the energy value of diets with dietary fat, particularly fats rich in saturated fatty acids, can result in the elevation of plasma total and lipoprotein cholesterol. In the present study, experimental diets were designed to examine the effects of increasing the energy content of diets with a saturated fat source and cholesterol in a non-purified diet on hyperlipoproteinaemia and aortic plaque composition in the atherosclerosis-susceptible Japanese quail (Coturnix japonica) model of human atherosclerosis. Commercial poultry diets containing two levels (i.e. 60 or 120 g/kg) of beef tallow as the primary source of saturated fat were balanced for endogenous cholesterol or supplemented with cholesterol (i.e. 0·5 or 5·0 g/kg) and fed to quail for 9 weeks to examine the effects on whole plasma, lipoprotein and aortic plaque lipid composition in relation to aortic plaque formation. Hypercholesterolaemia (P<0·001) was confirmed in birds fed on high-cholesterol (HC) diets only. An interaction (P=0·05) between dietary cholesterol and fat intake level was observed for plasma triacylglycerols (TG) and was specific to changes observed in VLDL composition. Diet-induced changes in lipoprotein total cholesterol, TG and phospholipid composition were greatest in the portomicron and VLDL fractions in birds fed on atherogenic diets. Hyperlipoproteinaemia induced by the 60 g/kg added beef tallow–HC diet resulted in significant (P<0·001) aortic plaque deposition, which was further enhanced in birds fed on the 120 g/kg beef tallow–HC diet. Quail fed on 120 g/kg beef tallow-HC diets exhibited the most severe aortic plaque formation, with marked increases in aortic tissue cholesterol content and quantifiable amounts of several cholesterol oxides (5,6α-epoxy-5α-cholesterol, 7β-hydroxycholesterol, cholestanetriol, 7-ketocholesterol and 25-hydroxycholesterol). In summary, hyperlipoproteinaemia associated with HC diets with a greater proportion of energy from saturated fat produced a combined effect in altering plasma and lipoprotein lipid composition as well as aortic tissue cholesterol and cholesterol oxide content in the Japanese quail.


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