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

Although hypertension, hyperlipidemia, diabetes and smoking are known risk factors of atherosclerosis in Caucasians, their relative contributions to early atherosclerosis among Japanese are unknown. Decrease in flow-mediated dilation (FMD) of the brachial artery is a useful marker of endothelial dysfunction and early atherosclerosis. To evaluate the relative contribution of hypertension to early atherogenesis, we determined FMD, as well as plasma levels of tissue-type plasminogen activator (t-PA; a sensitive index of endothelial damage) and tumor necrosis factor (TNF)-a and interleukin (IL)-6 (established markers of inflammation) in normotensive and hypertensive patients under treatment. FMD was significantly reduced as the number of risk factors increased, suggesting that accumulations of risk factors were related to endothelial dysfunction. FMD was reduced in hypertensives (9.9 +/- 5.8 (SD) %) compared to normotensives (14.6 +/- 7.6, p<0.01) despite good blood pressure control (139 +/- 20/80 +/- 14 mmHg in hypertensives). Nitroglycerine-induced endothelium-independent vasodilation was not altered in hypertensives (16.0 +/- 6.3%) as compared to normotensives (16.7 +/- 5.8). Plasma t-PA, TNF-alpha, and IL-6 levels were increased in hypertensives despite good blood pressure control. Thus, hypertension alone is a high risk for early atherosclerosis. Persistent endothelial damage and moderate inflammation may increase the risk of early atherosclerosis synergistically under the presence of hypertension in Japanese.
 ...
PMID:Association of cardiovascular risk factors and endothelial dysfunction in japanese hypertensive patients: implications for early atherosclerosis. 1213 29

A series of novel phenolic compounds has been discovered as potent inhibitors of TNF-alpha-inducible expression of vascular cell adhesion molecule-1 (VCAM-1) with concurrent antioxidant and lipid-modulating properties. Optimization of these multifunctional agents led to the identification of 3a (AGI-1067) as a clinical candidate with demonstrated efficacies in animal models of atherosclerosis and hyperlipidemia.
 ...
PMID:Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. 1218 56

Increased concentrations and activity of plasma cytokines produced by monocytes, macrophages, and hepatocytes in patients with alcoholic liver diseases, correlate with the clinical course of liver diseases and are of prognostic value. Especially, high levels of circulating tumor necrosis factor (TNF)-alpha have been found to correlate with increased mortality in alcoholic hepatitis. Moreover, hepatic RANTES was increased in patients with alcoholic hepatitis. Thus, TNF-alpha-induced RANTES expression may have a critical role in cell-mediated liver injury associated with alcoholic hepatitis. Fibrates are widely used in the treatment of hyperlipidemia and lower triglyceride levels in patients with hyperlipidemia. Recently, several groups reported that bezafibrate, one of fibrates, is effective in primary biliary cirrhosis treatment. Additionally, it is reported that bezafibrate is effective in the treatment not only of primary biliary cirrhosis but also of chronic hepatitis C and tamoxifen-induced non-alcoholic steatohepatitis. We, here, presented that bezafibrate and fenofibrate repressed TNF-alpha-induced protein production and mRNA expression of RANTES in human hepatocyte-derived cells. Luciferase assay showed that bezafibrate and fenofibrate inhibited RANTES gene expression in response to TNF-alpha. Moreover, bezafibrate repressed TNF-alpha-induced DNA-binding activity of NF-kappaB. Thus, fibrates reduced TNF-alpha-induced NF-kappaB activation and RANTES expression, possibly suggesting that fibrates might be inhibitory agents of migration of inflammatory cells by RANTES to the liver in patients with alcoholic liver diseases. In line of these results, it might be possible that fibrates are therapeutic agents in alcoholic liver diseases.
 ...
PMID:Inhibition of TNF-alpha-induced RANTES expression in human hepatocyte-derived cells by fibrates, the hypolipidemic drugs. 1258 3

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.
 ...
PMID:Brain-heart connection and the risk of heart attack. 1265 78

More and more recent studies demonstrate the pleiotropic effects of fibrates. Except lowering plasma lipid levels they can influence blood coagulation abnormalities and stabilise atherosclerotic lesions--a frequent result of the activation of inflammatory cells within the vascular wall. The anti-inflammatory action of fibrates includes inhibiting the release of many cytokines, such as Tumor Necrosis Factor e (TNF-alpha) by these cells. The aim of this study was to evaluate the effect of fenofibrate on the plasma levels of Plasminogen Activator Inhibitor type 1 (PAI-1) and fibrinogen in patients with combined dyslipidemia. Moreover, we assessed the amount of TNF-alpha released by peripheral blood isolated monocytes before and after therapy. Fourteen patients (8 women and 6 men) with hyperlipidemia IIb were treated with micronized fenofibrate (Lipanthyl 200 m, Fournier) in a daily dose of 200 mg for one month. The control group consisted of 12 individuals matched for age with biochemical confirmation of normolipemia. Plasma PAI-1 and TNF-alpha levels were measured by the ELISA method. Fibrinogen levels were measured according to the commonly used Clauss method. Before treatment the haemostatic compounds and TNF-alpha studied were significantly higher in the group with hyperlipidaemia IIb compared to the control group. One-month therapy with fenofibrate resulted in significant decrease of triglycerides and total cholesterol. After treatment, PAI-1 and fibrinogen levels also decreased significantly: PAI-1 from 101.18 +/- 9.74 ng/mL to 81.22 +/- 6.68 ng/mL, p < 0.01 and fibrinogen from 364.5 +/- 29.6 mg/dL to 294.7 +/- 19.3 mg/dL, p < 0.01. The study also revealed that the level of produced TNF-alpha decreased significantly from 2136.0 +/- 250.8 pg/mL to 1336.8 +/- 132.0 pg/mL, p < 0.05. These results may confirm new pathways of fibrates action.
 ...
PMID:[Pleiotropic effects of micronized fenofibrate in patients with combined hyperlipidemia]. 1266 42

Ethanol toxicity on liver is a function of duration of alcoholism, amount of daily intake of alcohol and patient's nutrition. The threshold of alcohol toxicity on the liver is about 40 g of ethanol daily in men and 20-30 g in women, however liver cirrhosis develops in no more than 8-20% of patients exceeding this values. Ethanol is oxidized in the liver to acetaldehyde--a compound considerably more toxic than ethanol itself. Despite small amount of alcohol dehydrogenase (ADH) found in gastric mucosa, the metabolism of ethanol in this site may have an important hepatoprotective effect. The oxidation of ethanol is associated with a change of hepatocyte redox homeostasis, which leads to a number of metabolic disorders such as lactic acidosis, hyperlipidaemia and hyperuricaemia. Chronic ethanol consumption does not influence ADH activity, but has a profound stimulatory effect on microsomal enzymes, in particular cytochrome CYP2E1. This fact is responsible for development in alcoholic liver associated with rise of oxygen consumption, excessive production of free radicals and increased metabolism of ethanol, vitamin A and testosterone. Ethanol and acetaldehyde have a deleterious effect, both the direct and indirect, on hepatocytes e.g., generating radical oxygen species and damaging intestinal mucosal barrier. Cellular oxidative stress that is caused by both an excess of free radicals and the antioxidatives' deficiency (glutathion, vitamin E, phosphatidylcholine), may be the principal factor responsible for progression of alcoholic liver disease. Among other factors accelerating alcohol-related liver lesion there are certain drugs, high fat diet, infection with HCV and genetic factors (female sex, enzymatic polymorphic forms of ADH and ALDH, hemochromatosis). Great importance in pathogenesis of necrotic and inflammatory hepatic events is being attributed to portal endotoxaemia and cytokines induced within the liver, in particular TNF-alpha and interleukin 8. These cytokines play a key role in development of alcoholic hepatitis, which clinical severity ranges from subclinical to fatal forms. Apart from abstinence, the treatment of alcohol liver disease is based on hyperalimentation, since alcoholism is generally associated with protein malnutrition. In severe forms of alcohol hepatitis corticosteroids are recommended.
 ...
PMID:[Alcoholic liver disease]. 1290 Dec 71

The association of elevated lipoprotein (a) (Lp(a)) with an increased risk for coronary events is clearly established. This increased risk may in part be due to the activation of monocytes as major cells involved in atherogenesis. High concentrations of plasma Lp(a) were shown to influence the gene expression of human blood monocytes and in the present study we demonstrate a reduced abundance of the lysosomal acid lipase (LAL) mRNA in monocytes of patients with coronary disease and selective Lp(a) hyperlipidemia. This is also supported by in vitro studies where purified Lp(a) but not low-density lipoprotein (LDL) was shown to downregulate mRNA levels of the LAL in control monocytes. A correlation of Lp(a) serum levels and the proinflammatory cytokine IL-6 was recently also described. Therefore, we investigated whether Lp(a) is capable to enhance the release of this acute phase cytokine from human blood monocytes. Purified Lp(a) led to an increased secretion of IL-6, but not TNF-alpha arguing against a general activation of these cells. The association of reduced LAL activity with the premature development of coronary artery disease has been demonstrated in patients with hypercholesterolemia, and in the present study we show for the first time that LAL expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a). In addition, increased levels of IL-6 also predict future cardiovascular events and IL-6 secretion was also induced by purified Lp(a).
 ...
PMID:Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes. 1297 90

Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolic alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.
 ...
PMID:[Adverse effects of antiretroviral therapy. Aspects of pathogenesis]. 1456 6

Recent progress in adipocyte-biology shows that adipocytes are not merely fat-storing cells but that they secrete a variety of hormones, cytekines, growth factors and other bioactive substabces, conceptualized as adipocytokines. These include plasminogen activator inhibitor 1(PAI-1), tumor necrosis factor(TNF-alpha), leptin and adiponectin. Dysregulated productions of these adipocytekines participate in the pathogenesis of obesity-associated metabolic syndrome such as insulin resistance, type 2 diabetes, hyperlipidemia, and vascular diseases. Increased productions of PAI-1 and TNF-alpha from accumulated fat contribute to the formation of thrombosis and insulin resistance in obesity, respectively. Lack of leptin causes metabolic syndrome. Adiponectin exerts insulin-sensitizing and anti-atherogenic effects, hence decrease of plasma adiponectin is causative for insulin resistance and atherosclerosis in obesity.
 ...
PMID:[Adipocytokines and metabolic syndrome--molecular mechanism and clinical implication]. 1520 45

To find out whether the expressions of these adipocyte markers are influenced by oriental medicine, obesity rats induced by high fat diet (HFD) for 8 weeks were injected with 50 mg/100 g body weight adlay seed crude extract (ACE), daily for 4 weeks. The results are summarized as follows: HFD + ACE group significantly reduced food intakes and body weights. Weights of epididymal and peritoneal fat were dramatically increased in HFD groups compared with those of normal diet (ND) group but significantly decreased more in HFD + ACE group than those of HFD + saline group (sham). Those of brown adipocytes were increased in HFD + ACE group compared to ND and sham groups but there was no significant difference. The sizes in white adipose tissue (WAT) by microscope were markedly larger in HFD groups than ND group but considerably reduced in HFD + ACE group compared with sham group. The levels of triglyceride, total-cholesterol and leptin in blood serum were significantly decreased in HFD + ACE group compared to those of sham group. Leptin and TNF-alpha mRNA expressions in WAT of rats were remarkably increased more in sham group than in those of ND group. Those of HFD + ACE group were significantly decreased compared with those of sham group, especially. TNF-alpha mRNA expression in HFD + ACE group was declined more than that of ND group. In conclusion, treatments of ACE modulated expressions of leptin and TNF-alpha and reduced body weights, food intake, fat size, adipose tissue mass and serum hyperlipidemia in obesity rat fed HFD. Accordingly, the oriental medicine extract, adlay seed crude extract, can be considered for obesity therapies controlling.
 ...
PMID:Hypolipidemic effects of crude extract of adlay seed (Coix lachrymajobi var. mayuen) in obesity rat fed high fat diet: relations of TNF-alpha and leptin mRNA expressions and serum lipid levels. 1523 96


<< Previous 1 2 3 4 5 Next >>