Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Abrupt withdrawal of HMG-CoA reductase inhibitors is associated with increased excretion of cholesterol into bile, but this phenomenon has not been investigated in humans. In order to evaluate whether patients interrupting these hypolipidemic drugs are at increased risk of forming gallstones, pravastatin (40 mg twice a day) or placebo was randomly administered to 16 bile fistula patients for 5 days. Biliary lipid composition was determined in basal conditions and for 5 consecutive days after drug withdrawal. Both biliary cholesterol concentration and saturation increased significantly on the second day after pravastatin withdrawal, but tended to decrease thereafter. Biliary bile acids and phospholipids were not affected. This short-lasting effect on biliary cholesterol excretion was probably the result of a transient increase of hepatic cholesterol synthesis by the up-regulated HMG-CoA reductase in the absence of the inhibitory drug. These results are consistent with the hypothesis that, also in humans, biliary cholesterol excretion could be dependent on the hepatic free cholesterol pool.
Atherosclerosis 1996 Jun
PMID:Effect of withdrawal of pravastatin on biliary lipid composition in humans. 878 44

The regulation of cholesterol metabolism by both genetic and environmental factors seems to be very complex. The recent research approach focusing on the genetic control of many key regulatory processes of cholesterol homeostasis has, however, started to elucidate the importance of genetic variation in susceptibility to a number of common clinical disorders such as hyperlipidemia, atherosclerosis, poor diet response, gallstone formation, colon tumours, and reduced lifespan.
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PMID:Genetics and cholesterol metabolism. 881 8

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is the intracellular enzyme responsible for the esterification of cholesterol with long-chain fatty acyl-CoA derivatives and has been implicated in atherosclerosis and gallstone disease. The effects of exogenous cholesterol and dithiothreitol (DTT) on the ACAT activity of human liver microsomes have been determined. Pre-incubation of microsomes with exogenous cholesterol gave a marked stimulation of activity. Experiments with [3H]cholesterol and [14C]oleoyl-CoA indicated the time course of equilibration of exogenous with endogenous cholesterol as ACAT substrates, and showed that ACAT activity could be accurately measured using [3H]cholesterol/Tween 80, providing that the concentration of endogenous microsomal cholesterol was also determined. Pre-incubation of liver microsomes for 90 min in the presence of 2 mmol/l DTT and exogenous cholesterol/Tween 80 resulted in a 60% reduction in ACAT activity, compared with the corresponding activity when DTT was omitted. If microsomes were pre-incubated with DTT prior to the pre-incubation with exogenous cholesterol/Tween 80, an 85-90% reduction in ACAT activity occurred. In contrast, pre-incubation of microsomes with DTT in the absence of exogenous cholesterol/Tween 80 (only endogenous cholesterol present) resulted, initially in a stimulation of ACAT activity; on further pre-incubation, activity returned to control levels. These results indicate that the supply of cholesterol to the enzyme active site is an important factor in ACAT assays in vitro and that DTT has a major effect on this process, suggesting that these factors may be important in controlling ACAT activity in vivo.
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PMID:Effect of exogenous cholesterol and dithiothreitol on the activity of human liver microsomal acyl-coenzyme A:cholesterol acyltransferase (ACAT). 896 Jul 84

The risk of atherosclerosis, a leading cause of cardiovascular disease and death, is inversely related to plasma levels of high-density lipoprotein (HDL) cholesterol, although the mechanism of this protective effect is unclear. The class B scavenger receptor, SR-BI, is the first HDL receptor to be well defined at a molecular level and is a mediator of selective cholesterol uptake in vitro. It is expressed most abundantly in steroidogenic tissues, where it is coordinately regulated with steroidogenesis by adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (hCG) and oestrogen, and in the liver, where its expression in rats is suppressed by oestrogen. Here we show that adenovirus-mediated, hepatic overexpression of SR-BI in mice on both sinusoidal and canalicular surfaces of hepatocytes results in the virtual disappearance of plasma HDL and a substantial increase in biliary cholesterol. SR-BI may directly mediate these effects by increasing hepatic HDL cholesterol uptake or by increasing cholesterol secretion into bile, or both. These results indicate that SR-BI may be important in hepatic HDL metabolism, in determining plasma HDL concentrations, and in controlling cholesterol concentrations in bile, and thus may influence the development and progression of atherosclerosis and gallstone disease.
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PMID:Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. 916 28

Cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis, has been implicated in atherosclerosis and gallstone disease. The aim of this study was to check if the use of hydroxypropyl-beta-cyclodextrin (HPBCD), a vehicle for solubilizing cholesterol, augmented the rate of 7 alpha-hydroxycholesterol formation in hamster liver microsomes compared to classical assays in which labeled cholesterol was delivered in Tween 80. We observed that [14C]cholesterol carried by HPBCD enhanced the sensitivity of the assay tenfold. However, linearity of 7 alpha-hydroxycholesterol formation with time was short because of the rapid transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one and 7 alpha,12 alpha-dihydroxy-cholesten-3-one when NADPH alone was present in the incubation medium. In order to avoid the transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one, which is essentially NAD(+)-dependent, but is also NADP(+)-dependent, NADPH (1 mmol/l) plus an NADPH-regenerating system must be present in the medium. In this improved assay, the optimal pH was 7.4 and the apparent Km for control and cholestyramine-fed hamsters had a similar value of 315 mumol/l; linearity in the formation of 7 alpha-hydroxycholesterol was also apparent after a relatively short time period (10 min), but with a markedly greater slope of the curve. With a short incubation time (6 min), microsomes from livers of hamsters (five and nine weeks old) that were fed with a commercial ground diet yielded rates of 7 alpha-hydroxycholesterol formation of 115 +/- 10 and 150 +/- 16 pmol/min.mg protein, respectively, whereas microsomes from hamsters fed with a lithogenic sucrose-rich diet (five weeks old) yielded rates of 7 alpha-hydroxycholesterol formation of 77 +/- 7 pmol/min.mg protein, which were significantly lower (-33%) than those of corresponding control hamsters. This improved cholesterol 7 alpha-hydroxylase assay is very sensitive, simple and rapid, and does not necessitate sophisticated equipment. It can be particularly useful for determining cholesterol 7 alpha-hydroxylase activity in liver biopsies from dyslipidemic or lithiasic patients.
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PMID:Improved assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by the use of hydroxypropyl-beta-cyclodextrin and an NADPH-regenerating system. 952 78

Primary aortoenteric fistulae (AEFs) are extremely rare vascular entities, with fewer than 250 cases reported in the world medical literature as of 1996. Incidence is less than 1 per cent, with a mortality ranging from 33 to 85 per cent. Atherosclerosis remains the most common etiology, accounting for more than two-thirds of the cases reported. Other etiologies include carcinoma, ulcers, gallstones, diverticulitis, appendicitis, and foreign bodies. Early diagnosis is crucial for survival and mandates recognition of the typical "herald bleed." Additional findings on initial presentation frequently include flank pain, abdominal pain, hematemesis, melena, and an abdominal mass. More than 80 per cent of primary AEFs involve the duodenum, with the overwhelming majority located in the third or fourth portion. Successful management of primary AEF requires a high index of suspicion for diagnosis and prompt surgical intervention for survival.
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PMID:Primary aortojejunal fistula: a case report. 992 48

Cholesterol crystal embolism is a serious complication of atherosclerosis resulting in renal, cutaneous and rarely digestive manifestations. We report two cases of systemic cholesterol crystal embolization with gallbladder involvement in two patients with gallstones, severe atherosclerosis with an abdominal aortic aneurysm as well as predisposing factors for cholesterol crystal migration. These two cases show that, like vasculitis, cholesterol crystal embolization may result in ischemic cholecystitis, and that diagnosis of cholesterol crystal embolization on routine cholecystectomy suggests severe systemic involvement and a poor prognosis.
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PMID:[Ischemic cholecystitis from cholesterol crystal embolism]. 1042 67

We review the beneficial and adverse effects of vegetarian diets in various medical conditions. Soybean-protein diet, legumes, nuts and soluble fibre significantly decrease total cholesterol, low-density lipoprotein cholesterol and triglycerides. Diets rich in fibre and complex carbohydrate, and restricted in fat, improve control of blood glucose concentration, lower insulin requirement and aid in weight control in diabetic patients. An inverse association has been reported between nut, fruit, vegetable and fibre consumption, and the risk of coronary heart disease. Patients eating a vegetarian diet, with comprehensive lifestyle changes, have had reduced frequency, duration and severity of angina as well as regression of coronary atherosclerosis and improved coronary perfusion. An inverse association between fruit and vegetable consumption and stroke has been suggested. Consumption of fruits and vegetables, especially spinach and collard green, was associated with a lower risk of age-related ocular macular degeneration. There is an inverse association between dietary fibre intake and incidence of colon and breast cancer as well as prevalence of colonic diverticula and gallstones. A decreased breast cancer risk has been associated with high intake of soy bean products. The beneficial effects could be due to the diet (monounsaturated and polyunsaturated fatty acids, minerals, fibre, complex carbohydrate, antioxidant vitamins, flavanoids, folic acid and phytoestrogens) as well as the associated healthy lifestyle in vegetarians. There are few adverse effects, mainly increased intestinal gas production and a small risk of vitamin B12 deficiency.
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PMID:Vegetarian diet: panacea for modern lifestyle diseases? 1087 92

We compared the effects of cholesterol feeding in male hamsters from two strains with different propensities to sucrose-induced cholelithiasis; Laboratoire de Physiologie de la Nutrition (LPN) hamsters are predisposed to developing biliary cholesterol gallstones, whereas Janvier (JAN) hamsters are not. When fed a basal control diet, LPN hamsters had a lower cholesterolemia (-21%, P = 0.01) than JAN hamsters, and a higher activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver (+148%, P = 0.018) and intestine (+281%, P < 0.0001). After feeding the same diet enriched with 0.3% cholesterol for 5 wk, cholesterolemia increased more dramatically in JAN hamsters (+235%, P < 0.001) than in LPN hamsters (+108%, P < 0.001), as did the liver concentration of cholesterol, which reached 152.30 +/- 13.00 and 44.41 +/- 9.06 micromol/g, respectively. Only JAN hamsters displayed hepatomegaly, with an increased cholesterol saturation index of the gallbladder bile (+100%, P < 0.01), due to the cholesterol challenge. In liver, cholesterol feeding reduced cholesterol 7alpha-hydroxylase activity and mRNA level, and stimulated sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase activities. Hepatic levels of LDL receptor decreased by approximately 60% in both strains, whereas HDL receptor scavenger class B type 1 (SR-BI) levels were unaffected by dietary cholesterol. The greater resistance of LPN hamsters to the hypercholesterolemic diet can be explained by a lower capacity to store cholesterol in the liver and greater efficiency in reducing the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in response to cholesterol feeding [from 11263 to 261 pmol/(min x organ) in LPN hamsters and from 4530 to 694 pmol/(min x organ) in JAN hamsters]. These results highlight the usefulness of this two-strain model, which offers some analogy with the inverse association between the predisposition to cholelithiasis and the risk of atherosclerosis in humans.
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PMID:Hamsters predisposed to sucrose-induced cholesterol gallstones (LPN strain) are more resistant to excess dietary cholesterol than hamsters that are not sensitive to cholelithiasis induction. 1138 71

Olive oil, the main fatty component of the Mediterranean diet, is characterized by consisting of monounsaturated fatty acids as well as by its elevated content in antioxidant agents. This oil exhibits numerous biological functions which are beneficial for the state of health. A diet rich in monounsaturated fatty acids provides an adequate fluidity to the biological membranes, diminishing the hazard of lipid peroxidation which affects polyunsaturated fatty acids. Moreover, the antioxidants present in olive oil are able to scavenge free radicals and afford an adequate protection against peroxidation. Regarding the heart, olive oil decreases the plasmatic levels of LDL-cholesterol and increases those of HDL-cholesterol, hence diminishing the risk of suffering from heart complaints. In this context, it has been suggested that increased consumption of monounsaturated fatty acids in place of polyunsaturated fatty acids will render circulating lipoproteins less sensitive to peroxidation and thereby diminish the development of atherosclerosis. Olive oil has also been proven to contribute to a better control of the hypertriglyceridemia accompanying diabetes and may reduce the risk of breast cancer and colorectum. On the other hand, several investigations have suggested that olive oil can be beneficial in inflammatory and autoimmune diseases, such as rheumatoid arthritis. In this sense, some reports have indicated that olive oil modifies inflammatory cytokines production. As for the digestive system, olive oil enhances gallbladder emptying consequently reducing cholelithiasis risk, decreases the pancreatic exocrine secretion and gastric secretory function in response to food. Finally, it has been demonstrated that a diet rich in olive oil is associated with a high percentage of gastric ulcer healing and affords a higher resistance against non steroidal antiinflammatory drugs-induced gastric ulcerogenesis.
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PMID:Mediterranean diet and health: biological importance of olive oil. 1147 48


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