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

One international and numerous national bodies have adopted action limits and guidelines for diagnosis and treatment of hyperlipidemia. The most publicized are those adopted by the European Atherosclerosis Society and by the National Cholesterol Education Program in the USA. Although differing in details, these guidelines share fairly low action limits based on observational epidemiology demonstrating increasing risk of cardiovascular disease in persons with serum cholesterol concentrations over 4-5 mmol/L. Various national bodies within Europe have adopted similar guidelines. In other countries, higher and therefore more conservative action limits have been proposed. They are primarily based on results of intervention studies. Seemingly small, differences between action limits may encompass a large part of the population.
 ...
PMID:Action limits in hyperlipidemia. 218 11

While the cholesterol concentration in a given tissue is similar in the rat, pig or man, the relative importance of the processes regulating the input (absorption and synthesis) and output (faecal cholesterol and bile acid excretions) of the cholesterol system is very different from one species to another. The rat, whose cholesterolaemia does not significantly increase after cholesterol addition to the diet ("hyporesponding" animal), successfully adapts its bile acid biosynthesis to variations in cholesterol input. This process accounts for 80 to 85% of cholesterol output, faecal cholesterol excretion being a minor process. The latter results from a low liver cholesterol secretion in the bile due to the low hydrophobicity of its main bile acids. Furthermore, in this animal a high intestinal synthesis of cholesterol and apolipoproteins (particularly B48) is observed. The latter are secreted as very light lipoproteins (chylomicrons and VLDL) with a faster plasma turnover than the VLDL (apoB100, E...) secreted by the liver. The "remnants" of rat VLDL are essentially very rapidly taken up by the liver; their interplasmatic transformation pathway into IDL and LDL is not very significant (less than or equal to 10%). Man, who has a more significant hypercholesterolaemia after exogenous cholesterol ingestion ("hyperresponding" subject) seems to have a less modulable capacity for transforming cholesterol into bile acids. This process accounts for only 50% of cholesterol output, faecal cholesterol excretion being quantitatively just as significant. Cholesterol concentration and the cholesterol/bile acid ratio are much higher in human than in rat bile, the main bile acids being more hydrophobic. While both the intestine and liver contribute to cholesterogenesis, the relative importance of the latter is probably greater in man than in the rat. Moreover, a larger fraction of plasma VLDL is transformed into IDL and LDL, the latter representing the main plasma cholesterol carrier. Determining whether the differences between the biodynamics of cholesterol processes in the rat and in man can be generalised to mammals with low or high sensitivities to hypercholesterolaemia and atherosclerosis seems to be a fundamental research objective for the next few years.
 ...
PMID:[Cholesterol and bile acid dynamics: comparative aspects]. 219 May 72

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
 ...
PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

Pharmacologic intervention for altering plasma lipoproteins is aimed principally at reducing atherogenesis and thereby preventing coronary artery disease. These drugs should be prescribed only after nonpharmacologic interventions (reduction of saturated fat and cholesterol consumption, weight reduction, aerobic exercise, cessation of cigarette smoking) have failed to achieve an adequate effect. The plasma concentration of the atherogenic low-density lipoprotein (LDL) may be reduced in hypercholesterolemic patients by increasing hepatic LDL receptor synthesis (bile acid sequestering resins, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) or by reducing hepatic very low density lipoprotein synthesis (gemfibrozil, nicotinic acid). LDL concentration may also be reduced by treatment with one of the fibrates (e.g., fenofibrate). Several classes of lipid-lowering drugs also increase the plasma high-density lipoprotein (HDL) cholesterol concentration. In the case of the fibrates, this appears to be principally mediated through an increase in lipoprotein lipase activity. Gemfibrozil additionally stimulates apolipoprotein AI synthesis. The increase in HDL cholesterol produced by nicotinic acid is due primarily to decreased clearance of HDL particles from the circulation. The increase in HDL concentration produced by gemfibrozil was shown in the Helsinki Heart Study to make a major contribution to a reduced incidence of coronary artery disease, independently of that made by the decrease in LDL. The Cholesterol-Lowering Atherosclerosis Study demonstrated that combined therapy with a resin (colestipol) and nicotinic acid can reduce the progression of coronary atherosclerosis and the development of graft lesions in patients who have undergone coronary artery bypass graft surgery.
 ...
PMID:Pharmacotherapy of disorders of plasma lipoprotein metabolism. 220 45

Cardiovascular disease (CVD) accounts for nearly half the deaths, yearly, in the United States. The arterio(athero)sclerotic plaque is the principal lesion of CVD. The White Carneau (WC) pigeon is an animal model that has been employed extensively for studying CVD. Cholesterol (CHOL) feeding aggravates atherosclerosis in WC pigeons greater than 2 years old. In 1986, two reports appeared from a single laboratory claiming a direct effect of drinking chlorinated (Cl) water upon lipid levels and plaque development in young (less than 1 year) WC pigeons. These are the only reports of such direct effects, to date. Three months' exposure to 2 ppm or 15 ppm Cl in the drinking water, resulted in increased circulating CHOL levels in young male WC pigeons fed a normocholesterolemic (NC) diet in which Ca2+ levels were reduced. In addition, at both Cl concentrations there was a significant increase in plaque size, compared to controls. Pigeons in the 2 ppm group also exhibited elevated low density lipoprotein (LDL) levels after 3 months on the NC diet. These findings, if extrapolated to man, could have considerable public health consequences, since nearly 200 million people in the United States drink Cl water. We have carried out a similar set of studies but with strikingly different results. We used the same suppliers of pigeons and feed as did the authors of the 1986 reports and followed their approach where possible. Six month-old male WC pigeons drank water with 2 ppm or 15 ppm Cl (pH 8.5) and ate a NC diet with Ca2+ reduced to 80% of normal. At both 1 and 3 months, body weight, CHOL, triglyceride and LDL levels were unaffected by drinking Cl water. There was also no effect of Cl water on plaque size after 3 months. Thus, we found no evidence that drinking chlorinated water has any effect upon circulating lipid levels or upon the development of arteriosclerotic plaques, in this animal model.
 ...
PMID:Ingestion of chlorinated water has no effect upon indicators of cardiovascular disease in pigeons. 221 28

The Cholesterol Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol-niacin therapy in 162 subjects. Two-year results (CLAS-I) showed decreased atherosclerosis progression and increased regression. We now describe a subgroup of 103 subjects treated for 4 years (CLAS-II). Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained, and at 4 years significantly more drug-treated subjects demonstrated nonprogression (52% drug- vs 15% placebo-treated) and regression (18% drug- vs 6% placebo-treated) in native coronary artery lesions. Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% drug- vs 40% placebo-treated) and bypass grafts (16% drug- vs 38% placebo-treated). These results confirm CLAS-I findings and indicate that regression can continue for 4 years. They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects.
 ...
PMID:Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. 200 70

This review primarily covers work on the effects of dietary n-3 fatty acids on lipoprotein metabolism and atherosclerosis that has been done in a nonhuman primate model, the African green monkey, and puts it in context with work of others using humans and other experimental animals. Detection of effects of n-3 fatty acids in the monkey model was facilitated by a considerable enrichment of dietary fat with fish oil (about 20% of dietary calories came from menhaden oil in the fish oil group or about 5 g/1000 cal of n-3 fatty acids). This group was compared with a group fed lard isocalorically substituted for fish oil, such that the percentage of saturated fatty acids was essentially equivalent in the 2 dietary groups. Cholesterol concentrations in whole plasma, LDL and HDL were about 1/3 lower in the fish oil group, as was apo A-I concentration, but apo B concentration was not different. The fish oil group had plasma LDL particles that were smaller, contained fewer cholesteryl ester molecules and had lower cholesteryl ester transition temperatures due to a relative enrichment of n-3 fatty acids in the CE fraction. In addition, hepatic cholesterol and cholesteryl ester concentrations were significantly lower in the animals fed fish oil. Liver perfusion was used to show that hepatic secretion of cholesterol and triglyceride was lower in the fish oil group, although the number of cholesterol and triglyceride enriched apo B-containing particles secreted was not different. We also demonstrated a lower plasma LCAT reactivity for the plasma phospholipids of the animals fed fish oil. Taken together, these findings clearly demonstrate important effects of n-3 fatty acids on cholesterol metabolism in a primate model that have not been previously recognized. In addition, the monkeys fed fish oil had less atherosclerosis in the coronary arteries and in the aorta. Thus, these findings indicate that, in addition to the many other effects of fish oil in eicosanoid production, fish oil effects on cholesterol metabolism, per se, can have an important role in limiting atherosclerosis.
Atherosclerosis 1990 Oct
PMID:Effect of fish oil on atherosclerosis and lipoprotein metabolism. 228 3

High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. Would a high K diet influence cholesterol ester deposits? In a normal rat on a normal diet, no cholesterol esters are detected in the aorta. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (.5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intraarterial blood pressures averaged 165 mm Hg in the normal K group and 161 mm Hg in the high K group (P = NS). The serum cholesterol averaged 229 mg/dL in the normal K group and 214 in the high K group (P = NS). Total aortic cholesterol esters per rat involving 16 and 18 carbon chain fatty acids averaged 187 micrograms in normal K v 68 micrograms in high K, measured by gas chromatography. These were the main esters; other esters were negligible. Thus high K reduced cholesterol ester deposits by 64% (P less than .0003), even though blood pressure and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of macrophages and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possible be useful for preventing atherosclerotic complications such as heart attacks in human hypertension.
 ...
PMID:High K diets markedly reduce atherosclerotic cholesterol ester deposition in aortas of rats with hypercholesterolemia and hypertension. 230 40

The effects of 3 beta-blockers with different pharmacological properties (non-selective: propranolol; beta 1-selective: metoprolol; and with intrinsic sympathomimetic activity: pindolol) were comparatively studied on LDL and lipid metabolism in human fibroblasts. At 10(-4) M, propranolol increased low density lipoprotein binding, uptake and degradation by 1.5-, 2.2- and 1.8-fold, respectively, whereas metoprolol and pindolol had no effect. This effect of propranolol is mainly due to an increase in LDL receptor number. Propranolol also enhanced sterol, triacylglycerol, fatty acid and phospholipid synthesis by 2-3-fold from sodium acetate. Cholesterol esterification by oleic acid was significantly and specifically decreased 4-fold by propranolol. Metoprolol and pindolol affect neither sterol synthesis nor cholesterol esterification. Pretreatment of cultured fibroblasts with propranolol induced an increase in hydroxymethyl-glutaryl-coenzyme A reductase activity and a decrease in acyl-coenzyme A: cholesterol-O-acyltransferase (ACAT) activity. Propranolol inhibited the induction of ACAT activity by exogenous cholesterol. Preincubation of a cell-free extract with propranolol also induced inhibition of ACAT activity. Propranolol decreased the cholesteryl ester content of cultured cells. These effects of propranolol on LDL and cholesterol metabolism might be related to the amphiphilic properties of the drug and suggest an effect on the cholesterol intracellular traffic. The decrease in cholesterol esterification and in the cholesteryl ester cellular level induced by propranolol may be involved in its antagonizing effect on experimental atherogenesis.
Atherosclerosis 1990 Mar
PMID:The antihypertensive drug propranolol enhances LDL catabolism and alters cholesterol metabolism in human cultured fibroblasts. 232 24

Cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured in 150 male survivors of first myocardial infarction and in 115 age and ethnic matched healthy controls. The total cholesterol concentration was higher in whites than in respective Asian groups and higher in patients than in controls (P less than 0.001). The ratio of cholesterol to HDL cholesterol was significantly higher in patients (P less than 0.001) and in both ethnic groups was a powerful independent predictor of cases. In Asians, the extent of coronary atheroma assessed by arteriography 2-12 weeks after infarction correlated independently with the total cholesterol concentration (P = 0.03). Thus, in Asian men, the lower level of total cholesterol compared to whites may be misleading. In Asian men the extent of atheroma correlated with the total cholesterol concentration and the relative risk of infarction increased with the ratio of total to HDL cholesterol. At a given level of cholesterol different ethnic groups may be at differing levels of cardiac risk and the cholesterol ratio may be a more appropriate means of inter-ethnic comparison.
Atherosclerosis 1990 Jul
PMID:Relationship between plasma cholesterol and coronary artery disease in Asians. 239 Jan 34


<< Previous 1 2 3 4 5 6 7 8 9 10