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)

Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.
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PMID:Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia. 1200 95

VLDL overproduction by enhanced hepatic FFA flux is a major characteristic of familial combined hyperlipidemia (FCHL). The postprandial complement component 3 (C3) response has been associated with impaired postprandial FFA metabolism in FCHL. We investigated the effects of 16 weeks of treatment with atorvastatin on postprandial C3 and lipid changes in 12 FCHL patients. Atorvastatin significantly lowered fasting plasma C3 and triglyceride (TG) in FCHL. Fasting TG and insulin sensitivity were the best predictors of fasting and postprandial C3. Postprandial triglyceridemia and C3 response, estimated as area under the curve (AUC), were significantly lowered by atorvastatin by 19% and 12%, respectively, albeit still elevated, compared with 10 matched controls. Postprandial FFA-AUC and postheparin plasma lipolytic activities remained unchanged after atorvastatin, suggesting no major effect on lipolysis. After atorvastatin, postprandial hydroxybutyric acid-AUC, which was elevated in untreated FCHL patients, was decreased, reaching values similar to those in controls. The present data show reduction of postprandial hepatic FFA flux in FCHL by atorvastatin, providing an additional mechanistic explanation for the reduction of VLDL secretion reported previously for atorvastatin. This was accompanied by a decrease in fasting plasma C3 concentrations and a blunted postprandial C3 response to an acute oral fat load.
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PMID:Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia. 1292 26

Atherosclerosis is the major cause of death in the world. Fasting and postprandial hyperlipidaemia are important risk factors for coronary heart disease (CHD). Recent developments have undoubtedly indicated that inflammation is pathophysiologically closely linked to atherogenesis and its clinical consequences. Inflammatory markers such as C-reactive protein (CRP), leucocyte count and complement component 3 (C3) have been linked to CHD and to hyperlipidaemia and several other CHD risk factors. Increases in these markers may result from activation of endothelial cells (CRP, leucocytes, C3), disturbances in adipose tissue fatty acid metabolism (CRP, C3), or from direct effects of CHD risk factors (leucocytes). It has been shown that lipoproteins, triglycerides, fatty acids and glucose can activate endothelial cells, most probably as a result of the production of reactive oxygen species. Similar mechanisms may also lead to leucocyte activation. Increases in triglycerides, fatty acids and glucose are common disturbances in the metabolic syndrome and are most prominent in the postprandial phase. People are in a postprandial state most of the day, and this phase is proatherogenic. Inhibition of the activation of leucocytes, endothelial cells, or both, is an interesting target for intervention, as activation is obligatory for adherence of leucocytes to the endothelium, thereby initiating atherogenesis. Potential interventions include the use of unsaturated long-chain fatty acids, polyphenols, antioxidants, angiotensin converting enzyme inhibitors and high-dose aspirin, which have direct anti-inflammatory and antiatherogenic effects. Furthermore, peroxisome proliferator activating receptor gamma (PPARgamma) agonists and statins have similar properties, which are in part independent of their lipid-lowering effects.
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PMID:Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis. 1576 89

We investigated the relationship between complement component 3 (C3), fasting and postprandial lipemia and the metabolic syndrome (MetabS). Herefore fasting and postprandial samples after an acute oral fat load were obtained in 40 MetabS+ (50+/-8 years) and 70 MetabS- (48+/-7 years) subjects. Fasting C3 was higher in MetabS+ (1.21+/-0.33g/L versus 0.91+/-0.14g/L, P<0.001). Postprandially, MetabS+ had a higher total and incremental triglyceride response (TG-AUC: +77%; P<0.001 and TG-dAUC: +48%; P<0.05, respectively) and a higher total free fatty acid (FFA-AUC: +13%, P<0.05) and C3 response (C3-AUC: +26%, P<0.001) when compared to MetabS-. In both groups, fasting C3 was strongly associated with fasting TG, TG-AUC, TG-dAUC and insulin sensitivity (HOMA) (R=0.68, 0.67, 0.41 and 0.67, respectively, for the whole group; P<0.001 for each). Fasting C3 showed a dose-dependent relation with the number of MetabS components and, following exclusion of these components, it was after TG-AUC, the second best determinant of the MetabS (adjusted R(2)=0.47, P<0.001). In conclusion, C3 and postprandial lipema are closely associated with the metabolic syndrome and with several metabolic variables linked to insulin resistance. C3 may be a useful marker to identify subjects with the metabolic syndrome.
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PMID:The metabolic syndrome in relation to complement component 3 and postprandial lipemia in patients from an outpatient lipid clinic and healthy volunteers. 1648 21

Hyperlipidemia has been well recognized as a striking feature of nephrotic syndrome and other renal diseases. However, the underlying pathophysiological mechanisms still have not yet been elucidated. In this study, we evaluated acylation-stimulating protein (ASP) and complement component 3 (C3) in children (n=48) with various forms of proteinuric renal disease [nephrotic syndrome, acute poststreptococcal infection glomerulonephritis (APSGN), and lupus nephritis (LN)] in comparison with age- and gender-matched controls (n=279). In children with proteinuric renal disease, various aberrations in plasma lipids were noted, including increased triglyceride, cholesterol, and low-density lipoprotein cholesterol (LDL-C) (all p<0.0001). Whereas C3 was not altered in children with nephrotic syndrome (1.05+/-0.05 g/L vs. 1.29+/-0.04 controls), the decrease was pronounced in children with LN and APSGN (0.42+/-0.11, p<0.05 and 0.30+/-0.06, p<0.001, respectively). Plasma C3 correlated positively with lipid parameters [triglyceride, cholesterol, LDL-C, apolipoprotein B (apoB), high-density lipoprotein cholesterol (HDL-C) and apoA1] and inversely with total protein, blood urea nitrogen, and creatinine. By contrast, plasma ASP was significantly elevated in all proteinuric renal diseases (101.4+/-7.1 nmol/L nephrotic syndrome, 90.9+/-14.1 LN, and 81.8+/-7.2 APSGN vs. 44.3+/-1.5 controls, p<0.05 to p<0.001), and this increase was correlated with changes in lipid parameters (triglycerides and apoA1). In summary, these results demonstrate alterations in C3 and ASP that may contribute to or compensate for dyslipidemia.
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PMID:Increased plasma acylation-stimulating protein in pediatric proteinuric renal disease. 1825 59

Postprandial hyperlipidemia is considered to be a substantial risk factor for atherosclerosis. Interestingly, this concept has never been supported by randomized clinical trials. The difficulty lies in the fact that most interventions aimed to reduce postprandial lipemia, will also affect LDL-C levels. The atherogenic mechanisms of postprandial lipids and lipoproteins can be divided into direct lipoprotein-mediated and indirect effects; the latter, in part, by inducing an inflammatory state. Elevations in postprandial triglycerides (TG) have been related to the increased expression of postprandial leukocyte activation markers, up-regulation of pro-inflammatory genes in endothelial cells and involvement of the complement system. This set of events is part of the postprandial inflammatory response, which is one of the recently identified potential pro-atherogenic mechanisms of postprandial lipemia. Especially, complement component 3 levels show a close correlation with postprandial lipemia and are also important determinants of the metabolic syndrome. In clinical practice, fasting TG are frequently used as reflections of postprandial lipemia due to the close correlation between the two. The use of serial capillary measurements in an out-of-hospital situation is an alternative for oral fat loading tests. Daylong TG profiles reflect postprandial lipemia and are increased in conditions like the metabolic syndrome, type 2 diabetes and atherosclerosis. Studies are needed to elucidate the role of postprandial inflammation in atherogenesis and to find new methods in order to reduce selectively the postprandial inflammatory response. Future studies are needed to find new methods in order to reduce selectively the postprandial inflammatory response.
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PMID:Novel aspects of postprandial lipemia in relation to atherosclerosis. 1859 82

Mannose binding lectin (MBL) is one of the three initiators of complement activation and is therefore closely linked to inflammation. MBL deficiency has been associated with the generation of atherosclerosis. Since atherosclerosis, the complement system and postprandial lipemia are linked to inflammation, we studied postprandial lipoprotein metabolism in MBL deficiency. An observational study was carried out in 107 volunteers (21% MBL deficient). Classical cardiovascular risk factors were not different between subjects with and without MBL deficiency. Oral fat loading tests in 8 MBL deficient and 14 MBL sufficient subjects showed similar postprandial triglyceride, free fatty acid, hydroxybutyric acid and complement component 3 concentrations. MBL deficient subjects had 2.4 times lower postprandial Sf>400 (chylomicron)-apoB48 concentrations, but in contrast a 2-3.5 times increased Sf 60-400 (VLDL1-TG) and Sf 60-400-apoB100 response. MBL activity was inversely related to the postprandial Sf 60-400-TG increase. Despite lower postprandial Sf>400-apoB48 concentrations, MBL deficient subjects show an accumulation of Sf 60-400 lipoproteins.
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PMID:Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects. 1938 Jan 35