Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1 versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 = .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were reduced compared with group 1 (P < .05). The K-value a measure of the LDL density, correlated with the the redox status (r = .37, P < .05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.
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PMID:The redox status of coenzyme Q10 in total LDL as an indicator of in vivo oxidative modification. Studies on subjects with familial combined hyperlipidemia. 901 47

The effects of marine omega-3 polyunsaturated fatty acids (FAs) and antioxidants on the oxidative modification of LDL were studied in a randomized, double-blind, placebo-controlled trial. Male smokers (n = 41) with combined hyperlipidemia were allocated to one of four groups receiving supplementation with omega-3 FAs (5 g eicosapentaenoic acid and docosahexaenoic acid per day), antioxidants (75 mg vitamin E, 150 mg vitamin C, 15 mg beta-carotene, and 30 mg coenzyme Q10 per day), both omega-3 FAs and antioxidants, or control oils. LDL and human mononuclear cells were isolated from the patients at baseline and after 6 weeks of supplementation. LDL was subjected to cell-mediated oxidation by the patients' own mononuclear cells, as well as to Cu(2+)-catalyzed and 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH)-initiated oxidation. Extent of LDL modification was measured as lag time, the formation rate of conjugated dienes (CDs), the maximum amount of CDs formed, formation of lipid peroxides, and the relative electrophoretic mobility of LDL on agarose gels. Dietary supplementation with omega-3 FAs increased the concentration of total omega-3 FAs in LDL and reduced the concentration of vitamin E in serum. The omega-3 FA-enriched LDL particles were not more susceptible to Cu(2+)-catalyzed, AAPH-initiated, or autologous cell-mediated oxidation than control LDL. In fact, enrichment with omega-3 FAs significantly reduced the formation rate of CDs when LDL was subjected to AAPH-induced oxidation. Supplementation with moderate amounts of antioxidants significantly increased the concentration of vitamin E in serum and increased the resistance of LDL to undergo Cu(2+)-catalyzed oxidation, measured as increased lag time, reduced formation of lipid peroxides, and reduced relative electrophoretic mobility compared with control LDL. Supplementation with omega-3 FAs/antioxidants showed oxidizability of LDL similar to that of control LDL and omega-3 FA-enriched LDL. In conclusion, omega-3 FAs neither rendered the LDL particles more susceptible to undergo in vitro oxidation nor influenced mononuclear cells' ability to oxidize autologous LDL, whereas moderate amounts of antioxidants protected LDL against oxidative modification.
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PMID:Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with omega-3 fatty acids and antioxidants. 940 30

There are findings indicating that a decreased ratio of plasma coenzyme Q10 (Q10) to LDL cholesterol could be associated with an increased risk of atherosclerosis. Furthermore, the proportion of plasma Q10H2 (reduced Q10, ubiquinol) of total Q10 has been shown to be attenuated in major diseases, such as hyperlipidemia and coronary artery disease. These observations suggest that measurement of plasma total Q10 and the proportion of plasma Q10H2 of total Q10 would be of clinical significance. However, epidemiological studies addressing this issue require large numbers of subjects, and measurements from unfrozen samples are unfeasible. For this reason, we evaluated the stability of Q10 samples during sample storage and processing. We also compared solid phase and hexane pre-treatments prior to high-performance liquid chromatographic determination of Q10. Our results indicate that samples for plasma total Q10 measurement can be pre-treated in normal laboratory lighting conditions, thawed and frozen several times, and stored deep frozen for a couple of years without changes in measured Q10 values. If purification of the samples by silica and C18 is needed, the best reproducibility tends to be achieved with powder treatment (not with cartridges). However, to measure successfully the proportion of plasma ubiquinol of total Q10, samples must be thawed, extracted, and analysed one at a time and quickly to ensure minimal ubiquinol oxidation during the measurement process.
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PMID:Measurement and stability of plasma reduced, oxidized and total coenzyme Q10 in humans. 1061 57

There is evidence that coronary artery disease (CAD), hypertension, diabetes mellitus (DM) and hyperlipidemia develop due to interaction of genetic and environmental factors during transition from poverty to affluence. Rapid transition in diet and lifestyle factors may influence heritability of the variant phenotypes that are dependent on the nutrient environment for their expression. We are beginning to recognize the interaction of specific nutrients with the genetic code possessed by all nucleated cells. In the next millennium, the physician may be able to make nutrient intake recommendations not on physical characteristics but on the basis of the individual's phenotypic expression for health while suppressing his phenotypic expression for disease. We have demonstrated an increased susceptibility to CAD, diabetes, central obesity, hyperinsulinemia and lipoprotein(a) excess in Indians in younger age groups indicating a genetic predisposition to these problems due to interaction of gene and environment. Lipoprotein(a) is a genetic risk factor for CAD, diabetes and stroke and it is higher in South Indians than North Indians. Antioxidant vitamins, coenzyme Q10 and n-3 fatty acids may have a beneficial influence whereas linoleic acid, saturated fat and sugars may have adverse effects on phenotypic expression. There is significant evidence that genes are involved in determining enzymes, receptors, cofactors, structural components involved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining an individual's risk. Majority of these genes are polymorphic. While some genes respond to nutritional modulation, others may not indicate any response.
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PMID:Genetic variation and nutrition in relation to coronary artery disease. 1122 22

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20). We measured the total radical-trapping antioxidant parameter (TRAP), single antioxidants (sulfhydryl groups, uric acid, vitamin C, alpha-tocopherol, coenzyme Q10), malondialdehyde, oxidized low density lipoprotein (LDL) antibodies, lipid profile [cholesterol, triglyceride, lipoprotein (a)], homocysteine, and hemoglobin (Hb)A(1C). TRAP levels were elevated in the GSD Ia group (p <.01) and correlated with elevated uric acid levels (r = 0.72, p =.001). None of the other plasma antioxidants correlated with TRAP levels. DMI patients showed decreased sulfhydryl groups (p <.01) and a reduced ubiquinol-10 fraction (p <.01). Malondialdehyde (p <.001) and oxidized LDL autoantibodies (p <.05) were increased in the diabetic group. In FH patients, parameters of oxidative stress and TRAP did not differ from controls. We conclude that in GSD Ia an increased antioxidative defense in plasma may protect against lipid peroxidation and thus against premature atherosclerosis. Furthermore, we demonstrated that in DMI increased oxidative mechanisms are already present in childhood.
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PMID:Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia. 1208 88

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.
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PMID:Coenzyme Q10 and cardiovascular disease: a review. 1259 59

Autonomic functions, such as increased sympathetic and parasympathetic activity and the brain's suprachiasmatic nucleus, higher nervous centres, depression, hostility and aggression appear to be important determinants of heart rate variability (HRV), which is, itself, an important risk factor of myocardial infarction, arrhythmias, sudden death, heart failure and atherosclerosis. The circadian rhythm of these complications with an increased occurrence in the second quarter of the day may be due to autonomic dysfunction as well as to the presence of excitatory brain and heart tissues. While increased sympathetic activity is associated with increased levels of cortisol, catecholamines, serotonin, renin, aldosterone, angiotensin and free radicals; increased parasympathetic activity may be associated with greater levels of acetylecholine, dopamine, nitric oxide, endorphins, coenzyme Q10, antioxidants and other protective factors. Recent studies indicate that hyperglycemia, diabetes, hyperlipidemia, ambient pollution, insulin resistance and mental stress can increase the risk of low HRV. These risk factors, which are known to favour cardiovascular disease, seem to act by decreasing HRV. There is evidence that regular fasting may modulate HRV and other risk factors of heart attack. While exercise is known to decrease HRV, exercise training may not have any adverse effect on HRV. In a recent study among 202 patients with acute myocardial infarction (AMI), the incidence of onset of chest pain was highest in the second quarter of the day (41.0%), mainly between 4.0-8.0 AM, followed by the fourth quarter, usually after large meals (28.2%). Emotion was the second most common trigger (43.5%). Cold weather was a predisposing factor in 29.2% and hot temperature (> 40 degrees celsius) was common in 24.7% of the patients. Dietary n-3 fatty acids and coenzyme Q10 have been found to prevent the increased circadian occurrence of cardiac events in our randomized controlled trials, possibly by increasing HRV. We have also found that n-3 fatty acids plus CoQ can decrease TNF-alpha and IL-6 in AMI which are pro-inflammatory agents. There is evidence that dietary n-3 fatty acids canenhance hippocampal acetylecholine levels, which may be protective. Similarly, the stimulation of the vagus nerve may inhibit TNF synthesis in the liver and acetylecholine, the principal vagal neurotransmitter, significantly attenuates the release of pro-inflammatory cytokines TNF-alpha, interleukin 1,6 and 18, but not the anti-inflammatory cytokine IL-10 in experiments. Therefore, any agent which can enhance brain acetylecholine levels, may be used as a therapeutic agent in protecting the suprachiasmatic nucleus, higher nervous centres, vagal activity and sympathetic nerve activity which are known to regulate the body clock and HRV and the risk of SCD and heart attack.
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PMID:Brain-heart connection and the risk of heart attack. 1265 78

Conditionally essential nutrients (CENs) are organic compounds that are ordinarily produced by the body in amounts sufficient to meet its physiological requirements. However, in disorders, such as cardiovascular disease (CVD), and in other physiologically stressful conditions, their biosynthesis may be inadequate. Under these circumstances, CENs become essential nutrients, comparable to vitamins. The CENs of primary importance in CVD, based on the quantity and quality of human clinical studies, are l-arginine, l-carnitine, propionyl-l-carnitine, and coenzyme Q10. Controlled studies of these CENs are reviewed in depth. Taurine is a CEN of secondary importance caused by a limited human database. Other putative CENs include alpha-lipoic acid, betaine, chondroitin sulfate, glutamine, and d-ribose, each of which is mentioned in passing. Collectively, CENs have demonstrated favorable clinical effects in CVDs, including chronic heart failure, myocardial infarction, angina pectoris, and in CVD risk factors, such as hypertension, hyperlipidemia, and lipoprotein(a). Limited research has pointed to possible benefits in CVD therapy accruing from supplementation with several CENs in combination. Additional controlled clinical studies of CENs in CVD are urgently needed. In view of the efficacy and safety of appropriate supplementation with CENs, it is strongly suggested that healthcare professionals become knowledgeable of these potentially important additions to the CVD therapeutic armamentarium.
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PMID:Supplemental conditionally essential nutrients in cardiovascular disease therapy. 1640 31

HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and cardiovascular morbidity in patients with hyperlipidaemia and those with coronary artery disease. However, evidence for statin treatment in patients with chronic heart failure (CHF) remains a subject of debate. Patients with heart failure were generally excluded in the existing trials and a different patient population with a distinct pattern of morbidity and treatment was studied. In addition, no safety data are available for statins in patients with heart failure, where there are potential concerns about coenzyme Q10 depletion and excessive low-density lipoprotein reduction. This review summarises the clinical and preclinical evidence for potential beneficial effects of statins in CHF. In experimental systems, statins have been shown to improve cardiac function through antioxidative and anti-inflammatory action. Statins improve endothelial function, may reduce neurohormonal activation, and stimulate endothelial progenitor cells. Some of these effects occur independently of cholesterol lowering and can be explained by inhibition of isoprenylation of signal transducing proteins of the family of Rho guanosine triphosphatases. Two ongoing controlled randomised trials (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure] and GISSI-HF [Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico--Heart Failure]) will help us to assess whether the described beneficial effects of statins in heart failure outweigh the potential negative effects and translate into the reduction of clinical endpoints.
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PMID:HMG-CoA reductase inhibitors in chronic heart failure: potential mechanisms of benefit and risk. 1645 Oct 90

Obesity is the major cause of type 2 diabetes with hyperlipidemia as one of its complications and antioxidants were found to be beneficial in such disease conditions. The present investigation is geared towards reduction of the dose required/improve the bioavailability of the combination of antioxidants, ellagic acid and coenzyme Q10 by co-encapsulating them into nanoparticles and study the possible synergism in ameliorating hyperlipidemia in high fat diet fed rats. The co-encapsulated particles at 10% (w/w of polymer) loading of ellagic acid and coenzyme Q10 have particle size of 260 nm. Male Sprague-Dawley (SD) rats on feeding high fat diet for over 4 weeks developed hyperlipidemia. The hyperlipidemic rats on 2 weeks post treatment with antioxidant combination administered as oral suspension or nanoparticles found to ameliorate the hyperlipidemic conditions and nanoparticles were found to be equally/more effective at 3 times lower dose in sustaining cholesterol lowering effect for extended periods, lowering glucose and triglycerides and in improving endothelial functioning, indicating the ability of the nanoparticles in improving efficacy of the duo. The results promise the potential of nanoparticles in improving the efficacy of ellagic acid and coenzyme Q10 in treating high fat diet induced hyperlipidemia in rats.
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PMID:The co-encapsulated antioxidant nanoparticles of ellagic acid and coenzyme Q10 ameliorates hyperlipidemia in high fat diet fed rats. 1990 93


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