Endothelial dysfunction, lipid peroxidation and cholesterol level in rabbit arteries: relationship to progressive hypercholesterolemia (original) (raw)
Related papers
Atherosclerosis, 2006
Endothelial dysfunction is characterized by impaired vasodilation, increase of oxidative stress and inflammation. The current study was designed to test the hypothesis that reversal of hypercholesterolemic diet alone does not normalize all the parameters of endothelial dysfunction. After 10 weeks on a high-cholesterol diet, female juvenile pigs were randomized to normal diet (n = 5, "Reversals") or continued on the same diet (n = 6, "HC") for another 6 weeks. A control group of 11 pigs received a normal diet ("C"). Coronary epicardial and arteriolar endothelial function was tested in vitro. NFB and p47phox expression was analyzed in epicardial arteries and myocardium, respectively. P47phox localization in coronary arteries was demonstrated with immunohistochemistry. Lipid levels normalized in Reversal pigs. Epicardial arteries of Reversals showed a normalized relaxation and NFB expression compared to HC (p < 0.05). Small vessel relaxation remained attenuated, and expression of p47phox in myocardial tissue was elevated in Reversals compared to C (p < 0.05). Dietary lowering of serum cholesterol and LDL improves vascular function of epicardial arteries but neither of small vessels nor vascular oxidative stress within this time frame. Hence, dietary normalization of serum lipid levels alone may not be synonymous to normalization of the components of endothelial dysfunction.
Experimental and Toxicologic Pathology, 2013
Background and objectives: The aim of this study is to verify the evolution and involution of experimental atherosclerosis in rabbits through the study of endothelial function, lipids and tissue lipid peroxidation, macro and microscopic quantification of aortic atherosclerosis. Methods: Thirty male New Zealand white rabbits were divided into six groups (n = 5): G1 normal diet; G2: hypercholesterolemic receiving 0.5% of cholesterol diet for 4 months; G3: hypercholesterolemic diet for 4 months after normal diet for more 4 months; G4: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 1 month, G5: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 2 months, G6: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 4 months. Rosuvastatin was administered at a dosage of 5 mg dissolved in 150 ml of water daily. At the end of the experiment were measured: total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), tissue cholesterol (CAO), lipid peroxidation tissue (MDA). Endothelial function (RMAX) was studied in a segment of thoracic aorta, through curve-effect of acetylcholine and sodium nitroprusside. The amount of atherosclerosis was determined by measurement of the arterial lesion, through software, after staining with Sudan IV and histological staining. Results: In relation the water the rabbits drank 60-70 ml all day. It was seen significantly increase in all parameters at G2 both biochemical and tissue. In the group G3 it was seen significantly decrease in plasma lipids levels and tissue cholesterol. Treated groups G4, G5 and G6 all showed a decreased plasma lipid levels, only at G6 group it was noted a tissue cholesterol, tissue peroxidation and quantification of atherosclerosis, which showed a significant decrease. In relation the endothelial function only G6 improve significantly. Interpretation and conclusions: Our findings indicated that the treatment with rosuvastatin for 4 months is more efficient because improve the endothelial function significantly.
Correction of enhanced endothelial permeability by cessation of cholesterol feeding
Journal of Vascular Surgery, 1987
Changes in endothelial permeability and the transport of macromolecules may be important in the initiation and/or progression of atherosclerosis. We have previously shown, with a carotid artery preparation isolated in situ with intact adventitia, that long-term cholesterol feeding in rabbits will result in a seven-to tenfold increase in '2~I albumin transport across the artery into the systemic circulation. The current studies were undertaken to determine whether this abnormality of enhanced permeability could be reversed by cessation of cholesterol feeding and correction of the hyperlipidemia. Two groups of rabbits were fed either a standard Rabbit Chow or a diet containing 1.5% cholesterol and 5.2% corn oil for 12 to 15 weeks. Another group of rabbits was given cholesterol for 12 to 15 weeks with change to standard rabbit chow for an additional 22 to 24 weeks after which albumin transport studies were then performed. Mean plasma cholesterol level after 12 to 15 weeks of cholesterol feeding was 2052 --395 mg/dl. After the animals were withdrawn from the cholesterol diet for 22 to 24 weeks, the mean plasma cholesterol level decreased to 80 -21 mg/dl. The mean plasma cholesterol value in chow-fed animals was 39 -6 mg/dl. Perfusion studies were done with 125I-labeled albumin and plasma radioactivity served as a measure of transport across the carotid artery. The average level of albumin transport across the artery into venous blood in the cholesterol-fed animals (13,911 dpm/ml of plasma) was significantly greater than that of control animals (2049 dpm/ml of plasma). The sevenfold increase in albumin transport induced by hypercholesterolemia was significantly reduced to near control levels by cessation of cholesterol feeding (3 750 dpm/ml of plasma). This occurred despite the absence of complete regression of intimal plaques by tissue lipid analysis or microscopic examination of the carotid arteries. These findings suggest that the enhanced permeability to albumin in the carotid artery induced by cholesterol feeding is reversed by cessation of a high cholesterol diet despite the persistence of intimal lesions. We can only speculate what role this correction of enhanced permeability plays in regression of atherosclerotic lesions. The results provide further evidence that cholesterol feeding induces functional changes in the arterial endothelium, which increases vascular permeability to albumin. (J Vasc SURG 1987;5:336-41.) Changes in arterial permeabilit T may be important in the initiation and development of atherosclerosis. Previous studies have shown that arterial endothelium provides a relative barrier to the uptake or transport of albumin. 14 We have previously From the Divisions 336 shown, with a carotid artery preparation isolated in situ with intact adventitia, that 3 to 6 months of cholesterol feeding in rabbits results in a seven-to tenfold increase in 125I-labeled albumin transport across the artery into the systemic circulation. 5 This increase in albumin transport was comparable to levels present in chow-fed animals in which the endothelium was mechanically denuded by an embolectomy catheter. Recent studies by us have demonstrated that this enhanced permeability to albumin can occur after cholesterol feeding for as short a period as 1 week. 6 This enchanced permeability occurred despite minimal morphologic changes, as seen by electron microscopy. We believe this to be a fu~:
Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits
Proceedings of the …, 1993
Recent evidence suggests that dietary therapy with lipid-soluble antioxidants may be beneficial for patients with atherosclerotic vascular disease but the potential mechanism(s) for these observations remain obscure. Abnormalities in endothelium-dependent control of vascular tone develop early in the course of atherosclerosis and may result from oxidative modification of low density lipoproteins. We examined the role of dietary antioxidants in preserving normal endothelial cell vasodilator function in cholesterol-fed rabbits with particular attention to possible effects on serum lipoproteins, low density lipoprotein oxidation, and atherogenesis. Male New Zealand White rabbits were fed diets containing no additive (controls), 1% cholesterol (cholesterol group), or 1% cholesterol chow supplemented with either g3-carotene (0.6 g/kg of chow) or a-tocopherol (1000 international units/kg of chow) for a 28-day period. After dietary therapy, thoracic aortae were harvested for assay of vascular function and for pathologic examination and tissue antioxidant levels. Compared to controls, acetylcholineand A23187-mediated endothelium-dependent relaxations were significantiy impaired in vessels from the cholesterol group (P < 0.001), whereas vessels from animals treated with-carotene or a-tocopherol demonstrated normal endothelium-dependent arterial relaxation. Preservation of endothelial function was associated with vascular incorporation of a-tocopherol and 3-carotene but was unrelated to plasma lipoprotein levels, smooth muscle cell function, or the extent of atherosclerosis. Increased low density lipoprotein resistance to ex vivo copper-mediated oxidation was observed only in the a-tocopherol group. Our results suggest that dietary antioxidants may benefit patients with atherosclerosis by preserving endothelial vasodilator function through a mechanism related to vascular tissue antioxidant content and not reflected by assay of low density lipoprotein resistance to ex vivo oxidation. The vascular endothelium is important in a number of homeostatic functions including the regulation of blood flow, vascular tone, and local platelet function (1, 2). Abnormalities of endothelium-derived relaxing factor (EDRF) action have been described in atherosclerosis (3) and hypercholesterolemia (4) and may contribute to the development of acute vascular syndromes. The oxidative modification of low density lipoprotein (LDL) has been implicated in both atherogenesis and the development of abnormal endotheliumdependent control of vascular tone (5, 6). Dietary antioxidants protect LDL against oxidation (7, 8) and limit experimental atherosclerosis (9), and epidemiologic evidence suggests that dietary antioxidants may prevent the clinical manifestations of coronary artery disease (10, 11). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Comparative atherogenic effects of cholesterol and cholesterol oxides
Atherosclerosis, 1986
Previous findings indicating that the oxidation products of cholesterol are associated with atherogenicity have led to a comparative study of the subchronic effects of feeding rabbits purified cholesterol, oxidized cholesterols free of cholesterol and cholesterol esters, or a mixture of cholesterol and oxidized cholesterols. Macroscopically, the cholesterol-fed animals exhibited 6-fold more arterial lesions than the animals fed cholesterol-free oxidized cholesterols. Microscopically, there was no statistically significant difference from the control in the number of histochemically-defined lesions in any of the groups. However, the lesions in the cholesterol-fed group were more severe, as indicated by a statistically significant increase in the magnitude of the lesions. This increased severity was also characterized by greater frequency and intensity of Azure A/Thionin, VonKossa, and Horseradish Peroxidase-Wheat Germ Agglutinin staining. Electronmicroscopic studies of normal appearing arterial tissues showed an increased density of viable smooth muscle cells and an increase in vacuolar extracellular debris in the cholesterol-fed group. Oxidized cholesterols in the concentrations and relative compositions administered here are markedly less atherogenie to rabbits than highly purified cholesterol.
Atherosclerosis, 1999
Oxidizability of isolated low density lipoprotein (LDL) and total antioxidative capacity of plasma were measured in rabbits fed for 6 weeks a cholesterol-rich diet and for further 34 weeks a normal diet. Whereas the time to induce copper ion-mediated lipid peroxidation in LDL was prolonged during hypercholesterolemia, total antioxidative capacity as determined by a radical-trapping assay was increased at 6 weeks, but decreased during the time when the plasma cholesterol levels declined slowly to normal. Since aortic plaque progression was continued also during the first 15 weeks of normal diet, increased atherogenicity of hypercholesterolemia might be better reflected by the antioxidant capacity of plasma rather than by oxidation of isolated LDL. : S 0 0 2 1 -9 1 5 0 ( 9 9 ) 0 0 0 4 7 -7