Cholesterol feeding enhances vasoconstrictor effects of products from rabbit polymorphonuclear leukocytes

1995 ◽  
Vol 269 (1) ◽  
pp. H1-H6
Author(s):  
J. L. Hart ◽  
C. G. Sobey ◽  
O. L. Woodman

We have studied the vasoactive properties of products released from rabbit polymorphonuclear leukocytes (PMNs) before and after short-term (4 and 8 wk) dietary supplementation with 1% cholesterol. Plasma cholesterol levels were similar after 4 and 8 wk of cholesterol diet, whereas gross atherosclerotic lesions were present at 4 wk but significantly more extensive after 8 wk. PMN products from all rabbits caused endothelium-dependent contraction of isolated, control (nonatherosclerotic) rabbit aorta submaximally contracted with phenylephrine. However, both 4 and 8 wk of cholesterol feeding resulted in equivalent contractions by PMN products, which were significantly greater than contractions by control PMNs. Endothelium-dependent contraction (by PMN products) and relaxation (by acetylcholine) were attenuated by 8 wk of cholesterol feeding. PMN products attenuated acetylcholine-induced relaxation of aorta from cholesterol-fed rabbits and of control aorta treated with phenoxybenzamine to reduce muscarinic receptor reserve. We conclude that elevation of plasma cholesterol results in increased release of a PMN product(s) that causes endothelium-dependent constriction.

1985 ◽  
Vol 63 (9) ◽  
pp. 1206-1209 ◽  
Author(s):  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda

Experiments were designed to assess the effect of cholesterol feeding on the endothelium-mediated relaxation of the rabbit aorta to acetylcholine. Age-matched male New Zealand white rabbits were fed either a 2% cholesterol diet or standard rabbit chow. The animals were anaesthetized with sodium pentobarbitone and sacrificed after 4 and 8 weeks on these diets. Rings were prepared from the proximal thoracic aorta and examined in tissue baths. These rings were contracted first with norepinephrine (−6 log mol/L) and acetylcholine was added to demonstrate the endothelium-mediated relaxation. The endothelium-dependent relaxation was significantly less in aortas from rabbits fed the 2% cholesterol diet than in aortas from animals fed the conventional diet. This impairment of relaxation was apparent after both 4 and 8 weeks of cholesterol feeding. In both groups of animals no relaxation was seen in rings from which the endothelium was removed. These results show that cholesterol feeding leads to an impairment of endothelium-mediated relaxation of the rabbit aorta to acetylcholine.


2006 ◽  
Vol 291 (6) ◽  
pp. H2987-H2996 ◽  
Author(s):  
C. M. C. Dupasquier ◽  
A.-M. Weber ◽  
B. P. Ander ◽  
P. P. Rampersad ◽  
S. Steigerwald ◽  
...  

Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol- and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the anti-atherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions.


2012 ◽  
Vol 8 (3) ◽  
pp. 106
Author(s):  
Krisnansari Diah ◽  
Ariadne Tiara Hapsari ◽  
Evy Sulistyoningrum ◽  
Agus Prastowo

Background: Nowadays, cardiovascular disease caused by hypercholesterolemia has become the main cause of death. Propolis has been used widely to reduce plasma cholesterol levels.Objective: The aims of this research was to study the effect of propolis on lipid profile of hypercholesterolemic Sprague Dawley rats.Method: This was an experimental study with pre-post test. Twenty four (24) male Sprague Dawley rats aged 12-16 week old, weighing 125-200 g were allocated into 4 groups. Group I received standard meal + aquadest-gavage; group II received high cholesterol meal + PTU 0,01 + aquadest gavage; group III received high cholesterol meal + PTU 0,01 + 0,027 g propolis gavage; group IV received high cholesterol meal + PTU 0,01 + 0,054 g propolis gavage. Total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol levels before and after treatment were measured. The data were then analyzed with One Way Anova.Results: The study showed that there were no significant differences in changes of body weight. There were significant differences in total cholesterol levels between all groups of treatment. Triglyceride levels were significantly different among all groups, except between group I and IV. Furthermore, the HDL cholesterol levels of group I vs III and group I vs IV were significantly different. However, there were no differences found in LDL cholesterol levels among all groups of treatment.Conclusion: Provision of 0,027 g and 0,054 g propolis improve lipid profile (total cholesterol, triglyceride and HDL cholesterol levels) of hypercholesterolemic rats.


1989 ◽  
Vol 61 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Susan L. Godfried ◽  
Gerald F. COMBS ◽  
James M. Saroka ◽  
Lloyd A. Dillingham

1. Two experiments were conducted to determine whether or not high dietary levels of vitamin E affect the development of atherosclerotic lesions in aortas of cholesterol-fed (5 g/kg diet) rabbits that were mechanically deendothelialized by balloon catheterization.2. In the first experiment, the aortas of rabbits fed 2000 mg vitamin E/kg diet (i.e. 50-fold their nutritional requirement) for 8 weeks showed no gross morphological differences, either within or outside experimentally damaged areas, from those of rabbits fed the nutritionally adequate control level (40 mg/kg) of the vitamin.3. In the second experiment, rabbits fed 10000 mg vitamin E/kg diet (i.e. 250-fold requirement) for 14–15 weeks showed significantly greater endothelial loss and plaque formation at aortic sites outside of the mechanically damaged area than did controls. Plasma cholesterol levels were very high (9000–14000 mg/1) and were not affected by dietary vitamin E level until 10–12 weeks when they were reduced moderately (18%).4. It is concluded that very high levels of vitamin E can potentiate spontaneous atherosclerotic lesions, and it is suggested that this effect may depend on high cholesterol status.


2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Jean-Marc Lavoie

Objective Metabolic disorders are often associated with liver steatosis and increased plasma cholesterol levels. However, the link between excessive lipid accumulation and impairments in cholesterol metabolism remains uninvestigated in the liver. Hence, a short treatment with a high-fat diet (HFD) was previously shown to promote excessive lipid accumulation in liver prior to the development of metabolic disorders. The present study intended to characterize how increases in liver fat alter the expression of several key regulators of hepatic cholesterol metabolism in response to a short-term HFD. Methods Young Wistar rats were randomly submitted either to HFD (n = 8) or a regular chow diet (RCD; n = 8) for 14 days.Liver tissue and blood were sampled . Results Increases in triglycerides were highly significant (P< 0.01) in liver but marginal in plasma of HFD rats. In contrast, the HFD resulted in higher (P< 0.01) cholesterol levels in plasma but not in liver samples. Gene expression of key markers involved in cholesterol uptake (LDL particles) including low density lipoprotein receptor-related protein-1 (LRP-1) and protein convertase subtilisin/kexin type 9 (PCSK9) along with ATP-binding cassette, superfamily G, member 5 (ABCG5) involved in cholesterol exportation viabile ducts were found to be higher (P< 0.05) in response to the HFD. In contrast, expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), involved in cholesterol synthesis was down-regulated in liver Conclusions The data support the concept that excessive accumulation of lipids promptly alters the expression of key genes regulating cholesterol metabolism in liver. On a clinical point of view, this indicates that increases in plasma cholesterol occur after a short-term high fat diet.


2019 ◽  
Vol 20 (14) ◽  
pp. 3515 ◽  
Author(s):  
Jinjie Wang ◽  
Kunxiang He ◽  
Chun Yang ◽  
Xiao Lin ◽  
Xin Zhang ◽  
...  

Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.


2020 ◽  
Vol 78 (1) ◽  
pp. 97-115
Author(s):  
Jade de Oliveira ◽  
Daiane F. Engel ◽  
Gabriela C. de Paula ◽  
Danúbia B. dos Santos ◽  
Jadna B. Lopes ◽  
...  

Background: Evidence has revealed an association between familial hypercholesterolemia and cognitive impairment. In this regard, a connection between cognitive deficits and hippocampal blood-brain barrier (BBB) breakdown was found in low-density lipoprotein receptor knockout mice (LDLr–/–), a mouse model of familial hypercholesterolemia. Objective: Herein we investigated the impact of a hypercholesterolemic diet on cognition and BBB function in C57BL/6 wild-type and LDLr–/–mice. Methods: Animals were fed with normal or high cholesterol diets for 30 days. Thus, wild-type and LDLr–/–mice were submitted to memory paradigms. Additionally, BBB integrity was evaluated in the mice’s prefrontal cortices and hippocampi. Results: A tenfold elevation in plasma cholesterol levels of LDLr–/–mice was observed after a hypercholesterolemic diet, while in wild-type mice, the hypercholesterolemic diet exposure increased plasma cholesterol levels only moderately and did not induce cognitive impairment. LDLr–/–mice presented memory impairment regardless of the diet. We observed BBB disruption as an increased permeability to sodium fluorescein in the prefrontal cortices and hippocampi and a decrease on hippocampal claudin-5 and occludin mRNA levels in both wild-type and LDLr–/–mice treated with a hypercholesterolemic diet. The LDLr–/–mice fed with a regular diet already presented BBB dysfunction. The BBB-increased leakage in the hippocampi of LDLr–/–mice was related to high microvessel content and intense astrogliosis, which did not occur in the control mice. Conclusion: Therefore, LDLr–/–mice seem to be more susceptible to cognitive impairments and BBB damage induced by exposure to a high cholesterol diet. Finally, BBB disruption appears to be a relevant event in hypercholesterolemia-induced brain alterations.


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.


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