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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
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PMID:The role of free radicals in disease. 761 52

Oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of coronary artery disease (CAD). Macrophages take up oxidized LDL via scavenger receptors, which is not regulated by cellular cholesterol contents, and oxidized LDL stimulates cholesterol esterification and this results in cellular cholesterol accumulation and foam cell formation. Several papers have reported a positive correlation between the severity of coronary atherosclerosis and the oxidative susceptibility of LDL. Small, dense LDL, LDL rich in polyunsaturated fatty acids (PUFA) or LDL poor in antioxidants (vitamin E, beta-carotene, CoQ10) should be more susceptible to lipid peroxidation and possibly more atherogenic. Therefore, to prevent CAD, it is important not only to reduce LDL cholesterol levels but also to suppress the oxidative modification of LDL.
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PMID:[Modified low-density lipoprotein]. 785 94

It has been postulated that lipid peroxidation plays a crucial role in the pathogenesis of atherosclerosis. As CoQ10H2 (reduced form of coenzyme Q10) is easily oxidized to CoQ10 (oxidized form of coenzyme Q10), it has been proposed that the CoQ10H2/CoQ10 ratio may be used as a possible marker of in vivo oxidative stress. However, sample preparation has an important effect on the redox status of coenzyme Q10 due to the extreme sensitivity of CoQ10H2 towards oxidation. We now report a rapid, simple isocratic HPLC procedure for the determination of CoQ10H2 and CoQ10 in plasma isopropanol extracts, and we used this method to investigate conditions by which the CoQ10H2/CoQ10 ratio can be reliably measured. Our results indicate that CoQ10H2 is unstable in whole blood, plasma, and isopropanol extracts; subsequently the CoQ10H2/CoQ10 ratio changes considerably soon after a blood sample has been obtained. The time period since blood sampling and HPLC analysis, as well as the sample pretreatment procedure, are two factors that have a profound effect on the pre-analytical variation in the determination of the CoQ10H2/CoQ10 ratio. If these two factors are properly controlled, the CoQ10H2/CoQ10 ratio may be a sensitive and practical way to measure in vivo oxidative stress. Furthermore, this indicator is independent from plasma total cholesterol concentrations, implying that groups who differ with respect to cholesterol levels may be compared directly.
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PMID:Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress. 882 Jan 3

Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10), is a potent lipophilic antioxidant present in nearly all human tissues. The exceptional oxidative lability of ubiquinol-10 implies that it may represent a sensitive index of oxidative stress. The present study was undertaken to assess the hypothesis that the level of ubiquinol-10 in human plasma can discriminate between healthy subjects and patients who are expected to be subjected to an increased oxidative stress in vivo. Using a newly developed method, we measured plasma ubiquinol-10 in 38 hyperlipidaemic patients with and without further complications, such as coronary heart disease, hypertension, or liver disease, and in 30 healthy subjects. The oxidizability of plasma samples obtained from hyperlipidaemic patients was found to be increased in comparison with control subjects, suggesting that the patients were subjected to a higher oxidative stress in vivo than the controls. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10 or normalized to plasma lipids, was lower in the patients than in controls (P = 0.001 and 0.008, respectively). The proportion of ubiquinol-10 decreased in the order young controls > aged controls > hyperlipidaemic patients without complications > hyperlipidaemic patients with complications (P = 0.003). A negative correlation was found between the proportion of ubiquinol-10 and plasma triglycerides. The hyperlipidaemic patients with hypertension had a lower proportion of ubiquinol-10 than subjects without. When the study population was divided into smokers and non-smokers, plasma ubiquinol-10 was found to be reduced amongst smokers, independently of whether it was expressed as a percentage of total ubiquinol-10 + ubiquinone-10 (P = 0.006) or normalized to plasma lipids (P = 0.009). These data suggest that the level of ubiquinol-10 in human plasma may represent a sensitive index of oxidative stress in vivo especially indicative of early oxidative damage. Measuring plasma ubiquinol-10 can be proposed as a practical approach to assess oxidative stress in humans.
Atherosclerosis 1997 Feb 28
PMID:Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia. 906 26

Evidence is rapidly accumulating that oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. In this study we measured the total peroxyl radical trapping capacity of human plasma LDL phospholipids (TRAPLDL) with a luminescent method. The study was carried out with 70 healthy volunteers, aged 28-77. In males an age-related decrease in TRAPLDL was observed. In the age group under 50 years the mean TRAPLDL was 31.36 +/- 1.45 pmol peroxyl radicals/nmol Pi; among those over 50 years it was significantly lower at 26.67 0.94 pmol/nmol Pi. As regards the components of TRAPLDL, the concentration of LDL-ubiquinol did not change and a non-significant decrease in the LDL-tocopherol concentration was detected with age. In females, the mean TRAPLDL, LDL-ubiquinol-10 and tocopherol concentrations did not differ between the age groups. When 17 of the participants were given coenzyme Q10 (Q10) supplementation, 100 mg/day, a highly significant increase in LDL-ubiquinol concentration was detected. Our results indicate that LDL antioxidant defenses tend to decrease with age in the Finnish male population. The decline is most significant in males under 50 years; in older age groups the values remain stable at a low level. Q10 supplementation doubles the number of ubiquinol-10-containing LDL molecules and may therefore have an inhibitory effect on LDL oxidation.
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PMID:Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins during aging: the effects of Q-10 supplementation. 926 12

Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol, has been suggested as an important anti-risk factor for the development of atherosclerosis as explained by the oxidative theory. Forty-five hypercholesterolemic patients were randomized in a double-blind trial in order to be treated with increasing dosages of either lovastatin (20-80 mg/day) or pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme Q10 were measured parallel to the levels of cholesterol at baseline on placebo and diet and during active treatment. A dose-related significant decline of the total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/- 0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/- S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001. Although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term therapy.
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PMID:Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. 926 15

The development of the atherosclerosis is mediated by the accumulation of oxidized lipids in the arterial wall. There is a relationship between average intake of dietary fat, its quality, and incidence of atherosclerosis. The goal of this work was to study the effect of different dietary fats on the coenzyme Q10 and hydroperoxide content of liver mitochondria in rabbits affected by an induced atherosclerosis. The results show that the induction of experimental atherosclerosis leads to a significant increase in hydroperoxides of rabbit liver membrane mitochondria and to a significant drop in the content of CoQ10. Furthermore, treatment of atherosclerotic rabbits with different diets resulted in an increase of membrane hydroperoxides in the group fed sunflower oil whereas the increase was significantly lower for animals fed virgin olive oil and fish oil stabilized with vitamin E (1 g/kg). CoQ10 levels only recovered partially in all groups; however, values in the sunflower oil were significantly lower as compared to corresponding values of the other groups. The use of either virgin olive oil or vitamin E stabilized fish oil in the dietary treatment of atherosclerosis appears to be a valid alternative for maintaining adequate levels of CoQ10 and hydroperoxides in liver mitochondria.
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PMID:Rabbit liver mitochondria coenzyme Q10 and hydroperoxide levels: an experimental model of atherosclerosis. 926 27

Treatment with oral coenzyme Q10 (CoQ10, 10 mg/kg per day for 6 days) was compared with no treatment in a previously described rabbit model of symptomatic cerebral vasospasm [Endo et al. (1988) Stroke 19: 1420-1425]. The treatment was initiated within 1-2 h after injection of autologous blood into the subarachnoid space. In CoQ10-untreated rabbits, moderate to severe neurological deficits developed, and multiple focal ischemic lesions were found in the brain regions with compromised blood supply, i.e., in the regions normally supplied by common carotid arteries which are subject to ligation in this model. CoQ10 treatment prevented the development of both the neurological deficits and histologically detectable brain tissue damage. In both CoQ10-treated and -untreated rabbits, infiltration of mononuclear cells was evident in the brain stem, although this region did not show signs of ischemic damage. The findings indicate that the histological and neurological correlates of brain tissue damage in this rabbit model of symptomatic cerebral vasospasm develop via mechanism(s) involving free radical-mediated oxidation of plasma lipoproteins. Similar mechanisms may play a role in the development of brain damage attributed to cerebral atherosclerosis.
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PMID:Oral coenzyme Q10 administration prevents the development of ischemic brain lesions in a rabbit model of symptomatic vasospasm. 934 38

Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.
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PMID:Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis. 1041 35

Greenlanders (Eskimos) have low prevalence of ischaemic heart disease, partly explained by a lower extent of atherosclerosis and a low n-6/n-3 ratio of polyunsaturated fatty acids. As atherosclerosis is also a result of oxidative stress, the total antioxidative readiness could have a substantial impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S-CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p < 0.001) compared to a Danish population. In a linear multiple regression model the S-CoQ10 level is significantly positively associated with age and S-selenium in males, and S-total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place, and it could probably be a substantial part of the antioxidative defense.
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PMID:High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study. 1041 47


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