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)

A simple and high resolution procedure of apoprotein E (apo E) phenotyping by isoelectric focusing with immobilized pH gradients and silver staining is described. This method needs delipidated very low density lipoproteins (isolated from 1 mL of serum) but obviates immunoblotting as well as neuraminidase treatment in routine applications because the sialylated forms are clearly separated. Immunoblotting (with polyclonal and monoclonal anti-apo E antiserum), cysteamine and neuraminidase treatment, and pI markers allowed the localization of three main alleles, xi 2, xi 3, xi 4 and the detection of variants or rare alleles (6/450 determinations). The serum amyloid A (SAA) apolipoproteins (SAA1,SAA2) could be characterized unequivocally (especially with E3 and E4). Silver staining proved more sensitive than Coomassie Brilliant Blue and needs only 5 micrograms of protein in the sample. The results of 403 normo-or hyperlipidemic patients are shown. In the group of 191 normolipidemic patients (cholesterol less than 6.40 mmol/L triglycerides less than 2 mmol/L), the relative frequency of the xi 3 allele (0.83) is higher than in other reports on Caucasians (about 0.77) whereas the xi 4 allele is lower. As previously described, we find a high frequency of the 4/3 phenotype in hypercholesterolemia and 3/2 in hypertriglyceridemia. The high frequency of the E2/E2 phenotype, usually associated with hyperlipidemia, and variants in complex hypertriglyceridemia makes the apo E phenotyping necessary in many cases of dyslipidemias.
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PMID:Apolipoprotein E phenotyping by isoelectric focusing in immobilized pH gradients and silver staining. 162 6

MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.
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PMID:Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice. 849 14

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
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PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.
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PMID:Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients. 1239 59

Low serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical, atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.
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PMID:Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis - interrelation with traditional cardiovascular risk factors. 1498 39

C-reactive protein (CRP) and serum amyloid A (SAA) are sensitive acute phase reactants. Both, but predominantly CRP in Japan, have long been used for monitoring inflammatory diseases. During the recent wave of measuring both at low concentration ranges and utilizing these values to clarity certain disorders involving low grade inflammation, we need to remain aware of factors other than apparent inflammation that can influence these values. These include age, obesity, hyperlipidemia, glucose intolerance, silent atherosclerosis, and therapeutic use of hypolipidemic agents or glucocorticoid. Genetic polymorphism may also be an influence; especially an allelic variant of SAA1 has been proposed to have a positive effect on SAA concentrations. Understanding this, these values should not be evaluated at a single sampling point but used kinetically in the individual.
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PMID:[Inflammatory markers; C-reactive protein (CRP) and serum amyloid A (SAA)]. 1602 85

The objective of the present study was to determine the effects that hemolysis, lipemia, bilirubinemia, and anticoagulants might have on the most commonly used assays for C-reactive protein and serum amyloid A, and determination of ceruloplasmin values in dogs. Solutions of hemoglobin, lipid, and bilirubin were added to serum aliquots. Additionally, serum and plasma samples with different anticoagulants (heparin, EDTA, and citrate) were obtained from healthy dogs. Hemolysis, lipemia, and hyperbilirubinemia interfered significantly with the C-reactive protein and ceruloplasmin results, but not with those for the serum amyloid A assay. The use of anticoagulants produced significant changes in the results for the assays tested. However, the magnitude of the differences caused by the interfering substances does not appear to have an important impact on the clinical interpretation of the tests.
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PMID:Effects of hemolysis, lipemia, hyperbilirrubinemia, and anticoagulants in canine C-reactive protein, serum amyloid A, and ceruloplasmin assays. 1615 18

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which cannot be explained by traditional risk factors alone. This study aims to investigate novel cardiovascular risk factors and cardiac event predictors in inactive SLE female patients who do not have any major cardiovascular risk factors. Twenty-five inactive (SLE disease activity index score <4) SLE female patients and 22 healthy control women were studied. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) were excluded. Venous blood samples were analyzed for lipid subfractions and novel cardiovascular risk factors such as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed by flow-mediated dilatation (FMD) from the brachial artery at baseline and during reactive hyperemia. SLE patients and controls were similar in terms of age (40+/-10 years vs 38+/-10 years, p = NS). No significant difference was found between the groups regarding family history of premature CAD, blood pressure, body mass index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B levels. Compared with the controls, SLE patients had higher levels of hs-CRP [median (range): 1.82 (0.02-0.98) vs 0.68 (0.02-0.35), p=0.04]. FMD was lower in SLE patients than controls (7.1+/-2.1 vs 11.4+/-1.2%, p<0.001). Increased levels of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP levels may reflect ongoing low-grade inflammation that could be a cause of impaired FMD in SLE patients. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of cardiovascular disease and future cardiac events.
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PMID:Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients. 1690 27

We developed a simple separative method for measuring serum amyloid A (SAA) in both high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) fractions. It was devised using the SAA agglutination method and phosphotungstic acid-Mg2+ precipitation procedure for evaluating HDL-cholesterol (HDL-C). The new method is also able to detect amyloid A (AA) in each fraction with precision. The results of both the present method and the method using SAA agglutination and the dextran sulfate-Mg2+ precipitation procedure showed a strong correlation when used to measure the level of SAA in the LDL fraction of patients (r = 0.997; p < 0.0001). Reference intervals in normal healthy subjects (n=75) ranged from 0.5 to 4.7 microg/ml in the HDL fraction and from 0.1 to 1.9 microg/ml in the LDL fraction. SAA in the LDL fraction of subjects with hyperlipidemia was significantly higher than in normal subjects and subjects with normal lipidemia. SAA in the HDL fraction and total sera of subjects with hyperlipidemia was significantly higher than in normal subjects; however, it was not higher than in patients with normal lipidemia. The present methods for detecting SAA, especially in the LDL fraction, might benefit from analyzing patho-physiological events in various lipid disorders.
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PMID:[A simple separative method for measuring serum amyloid A in high-density-lipoprotein and low-density-lipoprotein fractions using the phosphotungstic acid-Mg2+ precipitation procedure]. 1751 Dec 61

Adipose tissue secretes proteins like serum amyloid A (SAA), which plays important roles in local and systemic inflammation. Circulating SAA levels increase in obese humans, but the roles of adipose-derived SAA and hyperlipidemia in this process are unclear. We took advantage of the difference in the inducible isoforms of SAA secreted by adipose tissue (SAA3) and liver (SAA1 and 2) of mice to evaluate whether adipose tissue contributes to the circulating pool of SAA in obesity and hyperlipidemia. Genetically obese (ob/ob) mice, but not hyperlipidemic mice deficient in apolipoprotein E (Apoe(-/-)), had significantly higher circulating levels of SAA than their littermate controls. SAA1/2 mRNA expression in the liver and SAA3 mRNA expression in intra-abdominal fat were significantly higher in obese than thin mice, but they were not affected by hyperlipidemia in Apoe(-/-) mice. However, only SAA1/2 and the constitutive form of SAA (SAA4) could be detected in the circulation by mass spectrometric analysis of HDL, the major carrier of circulating SAA. In contrast, SAA3 could be detected in medium from cultured adipocytes. Our findings indicate that the expression of SAA3 in adipose tissue is upregulated by obesity, but it does not contribute to the circulating pool of SAA in mice.
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PMID:Serum amyloid A3 does not contribute to circulating SAA levels. 1928 46


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