Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.
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PMID:Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? 156 27

Plasma lipoprotein concentration and composition were studied in 7 female patients with primary biliary cirrhosis and compared with 6 normal, age-matched controls. The effect of the lipoproteins derived from these patients on the function of normal platelets was also tested. High levels of plasma cholesterol and phospholipids and a raised free/esterified cholesterol ratio were found. In 4 of the patients, both HDL cholesterol and HDL protein were increased, and high levels of plasma apoprotein A-I and A-II were evident. This abnormal HDL did not contain excess apolipoprotein E. The VLDL and LDL fractions were also abnormal, as evidenced by a high cholesterol/protein ratio. Little correlation between lipoprotein disorders and clinical condition was found. Platelet function was reduced in all patients. LDL from the patients reduced aggregation of normal platelets, whereas HDL had a minimal effect. The abnormal lipoproteins in these patients may contribute to their abnormal in vitro platelet aggregation.
Atherosclerosis 1984 Nov
PMID:Increased concentration of high density lipoprotein in plasma and decreased platelet aggregation in primary biliary cirrhosis. 651 71

Lipoprotein(a) (Lp(a)) is a unique lipoprotein, elevated serum levels of which are independently associated with an increased risk of coronary heart disease (CHD). Primary biliary cirrhosis (PBC) is often associated with high serum cholesterol, itself a risk factor for CHD. Despite this, patients with PBC are thought to have a lower than expected incidence of CHD. We hypothesised that this may be related to low serum levels of Lp(a) in PBC patients. This was investigated by collecting fasting blood samples from 42 patients with PBC, 39 age- and sex-matched subjects with non-PBC liver disease and 432 community control subjects. Serum was analysed for total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and apolipoproteins A1 and B (apo A1 and apo B). Lp(a) was measured by an enzyme-linked immunosorbent assay (ELISA) technique. There was a significant reduction of Lp(a) concentrations in the PBC group compared with the healthy controls (median value 28.5 mg/l vs. 75.0 mg/l, P < 0.005) and between the non-PBC liver disease group (median value 52.0 mg/l) and control group (P = 0.001). Within both the liver disease and PBC patient groups there were significant negative correlations between Lp(a) levels and bilirubin (R = -0.564, P < 0.001 and R = -0.395, P = 0.010 respectively). This preliminary study has demonstrated reduced Lp(a) levels in PBC patients which may be a contributory factor to explain a possible cardioprotective effect in such patients, despite elevated LDL cholesterol levels.
Atherosclerosis 1994 Jan
PMID:Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis. 815 87

We studied a selected group of 39 female patients suffering from primary biliary cirrhosis (PBC). This disease is characterized by typical lipoprotein alterations and elevated concentrations of serum cholesterol. Despite the increased concentration of atherogenic lipoproteins, enhanced atherogenesis is not characteristic of PBC. Serum total cholesterol, triglycerides, HDL2 and HDL3-cholesterol concentrations were measured by enzymatic methods or in combination with precipitation procedures. Apolipoproteins were determined by using immunonephelometric methods. ELISA sandwich method was used for lipoprotein(a) determinations. Apoprotein(a) phenotyping (isoforms) was performed by Western blotting with specific antibodies. The concentrations of serum lipids, lipoproteins and apoproteins (AI, AII and B) were found in the range of earlier investigations. The serum lipoprotein(a) concentration did not differ between the PBC patients and control subjects (10.0/0.1-54/, median 2.55 vs. 11.5/0-75/, median 5.2 mg/dl). In the advanced stages of PBC we found a higher number of patients with low lipoprotein concentration (lower than 1 mg/dl). In patients with shorter durations and milder histological alterations high HDL2 cholesterol subfractions has been detected (stage I = 0.42 +/- 0.18, stage II = 0.53 +/- 0.29 and stage III = 0.62 +/- 0.41 vs. stage IV = 0.26 +/- 0.15 mmol/l, P < 0.05). Despite the elevation of atherogenic lipoproteins, high HDL2-cholesterol and normal lipoprotein(a) concentrations may be one of the reasons why patients with advanced PBC are not placed at increased risk for atherosclerosis.
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PMID:Lipoprotein(a) concentration and phenotypes in primary biliary cirrhosis. 893 59

Patients with primary biliary cirrhosis (PBC) do not appear to have an increased risk of cardiovascular disease despite elevations in serum cholesterol. Recent evidence has pointed to LpA1 (an apo A1 containing particle which contains apo A1 but not apo A2) in protecting against atherosclerosis. The aim of this study was to investigate apo Al containing particles in the serum of patients with PBC. Lipids and apolipoproteins were measured in 31 patients with PBC (30 females) and 27 control subjects (26 females). Patients were divided into 3 groups: group 1 with bilirubin < 18 micromol/l (n = 17); group 2 with bilirubin > 18 micromol/l (n = 11); and group 3 with end stage liver disease (ESLD, n = 3). As expected group 1 and 2 patients had higher total cholesterol, HDL cholesterol and phospholipids than control subjects. Apo B and apo A1 concentrations were similar to control subjects. However, LpA1 was greatly increased: 0.96 g/l (0.60-1.50), median (range) in group 1 and 1.09 g/l (0.75-1.33) in group 2 versus 0.62 g/l (0.45-0.93) for controls both P < 0.005 and the percentage of total apo A1 in the LpA1 fraction was increased: 54.8% (37.9-63.4) in group 1 and 55.7% (47.8-73.7) in group 2 versus 36.8% (25.1-49.1) for controls, both P < 0.005. Apo A2 concentration was reduced in group 1 0.38 g/l (0.30-0.51) and group 2 0.31 g/l (0.14-0.58) versus controls 0.43 g/l (0.36-0.57), P < 0.05 and P < 0.005 respectively. Patients with ESLD had reduced HDL cholesterol, apo A1, LpA1 and apo A2 compared to controls. These results suggest that PBC is associated with an altered distribution of apo A1 favouring an increased concentration of the protective LpA-I particles. Increased LpA1 concentration may be one of the factors contributing to the paradoxically low incidence of atherosclerosis in PBC patients.
Atherosclerosis 1997 Jun
PMID:Abnormalities of serum apo A1 containing lipoprotein particles in patients with primary biliary cirrhosis. 919 73

Administration of ursodeoxycholic acid (UDCA) has been shown to decrease serum total and low density lipoprotein (LDL) cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that the cholesterol-lowering effect of UDCA may be due, at least in part, to a direct increment in hepatic LDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al., Lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellular LDL receptor recruitment, as determined by its effect in vivo on LDL uptake, and its effect in vitro on LDL binding, under conditions of moderately elevated serum cholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chow diet (control), a 0.15% cholesterol-containing diet, or a 0.15% cholesterol-containing diet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA). Cholesterol feeding increased (P<0.01) total serum cholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamster LDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed a cholesterol-containing diet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated human LDL, a marker of LDL receptor-independent LDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamster LDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by either cholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed a cholesterol-supplemented diet. In conclusion, in dietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepatic LDL binding and uptake to levels observed in control hamsters.
Atherosclerosis 2000 Nov
PMID:Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters. 1105

IL-18 is a pleiotropic cytokine and is produced by various types of cells including activated macrophages, particularly Kupffer cells. IL-18 has potential to activate inflammatory responses through induction of IFN-gamma production in collaboration with IL-12. Somewhat paradoxically, IL-18 also has the capacity to induce allergic responses via induction of IL-4 production by T helper cells and to activate mast cells and basophils to release atopic effector molecules such as histamine. Indeed, IL-18 is involved in inflammatory tissue injuries, such as Crohn's disease and atherosclerosis, and also in hyper IgE and atopic dermatitis. IL-18 is particularly important for induction of experimental liver diseases. Endotoxin-induced liver injury or Fas ligand-induced hepatitis is caused by endogenous IL-18 in mice. Moreover, patients with liver diseases such as fulminant hepatitis, liver cirrhosis due to hepatitis virus infection and primary biliary cirrhosis show elevation of serum levels of IL-18, that correlates with the corresponding disease severity. Therefore, endogenous IL-18 plays a major role in induction of some types of liver injuries in mice and human. NKT cells that express both T cell receptor and NK cell marker are abundant in the liver of mice and human. Recent studies have revealed that NKT cells participate in some types of liver injuries, such as concanavalin A-induced T cell-mediated hepatitis and malaria hepatitis. In this review article, we focus on IL-18-involving liver damages and NKT-cell-mediated liver injuries.
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PMID:Cytokine-induced inflammatory liver injuries. 1452 86

Hypercholesterolemic human LDL contains oxidized subfractions that have atherogenic properties. Paradoxically, atherosclerosis incidence is low in patients with primary biliary cirrhosis (PBC), a disease characterized by marked increases in plasma LDL, including the LDL subfraction lipoprotein-X (Lp-X). To investigate the mechanisms underlying this paradox, we first examined the propensity to oxidation of unfractionated LDL isolated from PBC patients. After prolonged incubation with copper, PBC-LDL failed to increase the oxidation index or electrophoretic mobility noted in control LDL. An admixture of PBC-LDL or Lp-X with control LDL prevented oxidation of the latter in a dose-dependent manner. PBC-LDL was also noncompetitive against copper-oxidized LDL (oxLDL) for binding with a murine monoclonal anti-oxLDL antibody in a competitive ELISA. OxLDL exerts its proapoptotic and antiangiogenic effects in part by inhibiting fibroblast growth factor 2 (FGF2) expression. Preincubation of oxLDL with PBC-LDL, but not control LDL, attenuated the inhibitory effects of oxLDL on FGF2 expression in cultured bovine aortic endothelial cells (ECs). The antioxidant and prosurvival properties of PBC-LDL diminished after the patients underwent orthotopic liver transplantation. These results suggest that Lp-X reduces LDL atherogenicity by preventing LDL oxidation to protect EC integrity in the presence of hypercholesterolemia. They also suggest that altering LDL composition may be as important as reducing LDL concentration in preventing or treating atherosclerosis.
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PMID:Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation. 1531 1

Primary Biliary Cirrhosis (PBC) is a chronic, progressive liver disease associated with markedly elevated serum lipids, but it is not clear if PBC is associated with accelerated atherosclerosis. The present systematic review examined the relationship of PBC to atherosclerotic risk. The lipid abnormalities in PBC are complex, depend on the stage of hepatic dysfunction and affect most lipoprotein classes. Increased cholesterol levels in PBC are primarily due to LP-X, an abnormal LDL particle. LP-X has anti-atherogenic properties and may reduce the atherosclerotic risk. Few studies have examined coronary artery disease (CAD) events in PBC, and none have sufficient sample size of follow-up to determine CAD risk in PBC patients. Nevertheless, one study suggested that 12% of PBC patients died from circulatory system diseases suggesting that lipid treatment is appropriate in some patients. Additional larger scale, prospective studies are required to determine the necessity of lipid treatment in this patient group. In the interim, decisions on the use of lipid lowering agents depend largely on the prognosis of the PBC and physician and patient preference for treatment.
Atherosclerosis 2007 Oct
PMID:Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. 1724 Mar 80

Increased concentration of lipid peroxidation products in patients with primary biliary cirrhosis is related to elevation of serum lipid content, but not to activation of lipid peroxidation. Hyperbilirubinemia in patients with primary biliary cirrhosis is accompanied by a decrease in the concentration of lipid peroxidation products and increase in antioxidant activity of blood serum. Antioxidants play a major role in the prevention of atherosclerosis. We hypothesized that the absence of increased risk of atherosclerosis in patients with primary biliary cirrhosis is due to inhibition of lipid peroxidation in blood serum by antioxidant compound bilirubin.
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PMID:Primary biliary cirrhosis and coronary atherosclerosis: protective antioxidant effect of bilirubin. 1902 93


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