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)

Previous reports in which cholesterol homeostasis has been examined in patients with phenotypic abetalipoproteinemia have shown an increase in whole body cholesterol synthesis when measured by sterol balance techniques but normal rates of cholesterol synthesis when measured by isotopic cholesterol turnover. Recent studies have indicated that increases in cholesterol biosynthesis are paralleled by increases in the plasma concentrations of mevalonic acid and by higher rates of excretion of mevalonic acid in the urine. In the present report we have measured the 24-h urinary excretion of mevalonic acid in 7 patients with phenotypic abetalipoproteinemia and compared this to control subjects. Urinary excretion of mevalonic acid was significantly higher in the patients with abetalipoproteinemia (57.2 +/- 10.2 nmol/kg body weight per day, mean +/- SEM) as compared to control subjects (23.1 +/- 1.5 nmol/kg per day). The magnitude of the increase in urinary mevalonic acid excretion seen in patients with abetalipoproteinemia (148%) is greater than the increase in whole body cholesterol biosynthesis assessed by sterol balance techniques (57% increase). Our results serve to further validate the usefulness of urinary mevalonate as an indicator of relative rates of cholesterol biosynthesis in humans and suggest that this measurement provides a valuable means to potentially screen for disorders associated with an oversynthesis of cholesterol.
Atherosclerosis 1989 Mar
PMID:Increased urinary mevalonic acid excretion in patients with abetalipoproteinemia and homozygous hypobetalipoproteinemia. 292 62

Ventricular dysfunction induced by dipyridamole would be evidence of myocardial ischemia in patients with limited ability to undergo standard exercise testing. Radionuclide ventriculography before and after intravenous dipyridamole infusion was compared with the results of exercise radionuclide ventriculography in a prospective study of 31 patients undergoing coronary angiography. Among these patients, 21 (68%) had significant coronary artery disease (greater than or equal to 50% stenosis), 19 (61%) had severe coronary disease (greater than or equal to 70% stenosis) and 10 (32%) were "normal" (less than 50% stenosis). The left ventricular ejection fraction was calculated, and regional wall motion was scored on a 6 unit scale. In the normal patients, the ejection fraction (+/- SEM) increased 5.6 +/- 2% (units) during exercise and 7.9 +/- 1 units after dipyridamole (both p less than or equal to 0.004 compared with that during rest). However, in patients with coronary artery disease, the ejection fraction failed to increase during exercise or after dipyridamole. In the patients with coronary artery disease, regional wall motion decreased by 4.1 +/- 0.5 units during exercise (p less than 0.003) and by 1.8 units after dipyridamole (p less than 0.02). Receiver operating characteristic analysis demonstrated general comparability between the sensitivity and specificity of exercise and dipyridamole ventriculography, with "optimal" operating points that favored choosing high sensitivity for the former and high specificity for the latter. Specific subsets of patients with severe coronary atherosclerosis were analyzed with use of these criteria. In patients with severe stenosis (greater than or equal to 70%), the sensitivity of dipyridamole ventriculography was 67% compared with 89% for exercise ventriculography. However, at these levels of sensitivity, the specificity of dipyridamole ventriculography was 92% compared with 67% for exercise ventriculography. In this and other subsets of patients, the specificity of dipyridamole ventriculography exceeded that of exercise ventriculography. Thus, it is concluded that dipyridamole radionuclide ventriculography is moderately sensitive and highly specific for detecting severe coronary atherosclerosis. This technique provides a widely applicable, useful alternative to exercise ventriculography in the diagnosis of coronary atherosclerosis in patients who have limited exercise tolerance.
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PMID:Dipyridamole radionuclide ventriculography: a test with high specificity for severe coronary artery disease. 292 38

We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo- and PN 200110-treated groups. The respective values averaged 2140 +/- 116 (n = 14; mean +/- SEM) and 2012 +/- 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 +/- 5% of the intimal surface, and the aortic cholesterol concentration was 72 +/- 6 mg/g protein. Corresponding values in aortas from PN 200110-treated rabbits were significantly lower [36 +/- 5% (P less than 0.03) and 52 +/- 3 mg/g protein (P less than 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P less than 0.01) and averaged 31 +/- 4% and 61 +/- 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylcholine, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation.
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PMID:Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110. 293 28

Aortocoronary vein bypass surgery might not restore normal maximal coronary flow reserve to bypassed coronary vessels because residual diffuse coronary atherosclerosis might limit maximal hyperemia. To investigate the effect of diffuse atherosclerosis and a focal stenosis at the graft-coronary anastomosis, we measured coronary flow reserve with an extensively validated subselective Doppler catheter in 24 patients with 35 bypass grafts perfusing angiographically normal coronary vessels. The Doppler catheter was positioned in the midportion of the graft, and coronary flow reserve was measured as the peak/resting velocity ratio after selective graft injection of a maximally vasodilating dose of papaverine. Luminal dimensions of the bypass graft, graft-coronary insertion, and bypassed coronary vessel were measured by quantitative coronary angiography (Brown/Dodge method). Measurements of coronary flow reserve and coronary dimensions of vein bypass grafts were compared with similar measurements obtained from 13 patients with normal coronary vessels and normal myocardium. Seventeen of the 35 bypass grafts perfused unobstructed coronary-vein graft anastomoses (less than 50% area stenosis) and normal myocardium. The coronary flow reserve of these 17 bypass grafts was normal (5.0 +/- 0.4, mean +/- SEM) and not significantly different from that measured in normal arteries (5.1 +/- 0.6), even though the cross-sectional area of the native coronary artery just distal to the bypass insertion was 40% smaller than in matched normal vessels. Bypass grafts perfusing hypertrophied (n = 2) or infarcted (n = 6) myocardium had significantly reduced coronary flow reserve compared with normal vessels (2.7 +/- 0.3; p less than .01), even when the infarcted wall had only minimal hypokinesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does coronary artery bypass surgery restore normal maximal coronary flow reserve? The effect of diffuse atherosclerosis and focal obstructive lesions. 295 10

Cardiac transplantation is frequently associated with accelerated coronary atherosclerosis and immune-mediated microvascular injury. To determine if orthotopic cardiac transplantation impairs the capacity of the coronary vasculature to vasodilate and conduct hyperemic blood flow, maximal coronary vasodilator reserve was measured in 25 cardiac allograft recipients with no evidence of rejection 6-57 months after transplantation and in 20 normal subjects. Left ventricular wall thickness was assessed echocardiographically, and epicardial coronary anatomy was evaluated by quantitative coronary angiography. Coronary vasodilator reserve (CVDR) was measured in all patients with a coronary Doppler catheter and a maximally vasodilating dose of intracoronary papaverine. CVDR measured in the transplant recipients with normal coronary arteries, left ventricular function, and wall thickness (5.0 +/- 0.3 [mean +/- SEM] peak/resting velocity; range, 3.8-7.3; n = 16) was not different from that of normal subjects (4.8 +/- 0.2; range, 3.7-8.3). CVDR in the five cardiac allograft recipients with diffuse coronary atherosclerosis producing 30 +/- 5% narrowing (range, 25-38%) of epicardial vessel diameter also was normal (5.1 +/- 0.3; range, 4.3-6.2; n = 5). The CVDR was reduced, however, in two of the four cardiac allograft recipients with left ventricular hypertrophy. In the only transplant recipient in whom a regional wall motion abnormality was present, CVDR was abnormal in the vascular distribution of the hypokinetic wall segment (1.8) but was normal in the artery that supplied normally functioning myocardium (4.0). These findings demonstrate that in the absence of allograft rejection, acquired left ventricular hypertrophy, and regional wall motion abnormalities, coronary vasodilator reserve is normal after orthotopic human cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary vasodilator reserve after human orthotopic cardiac transplantation. 297 19

A semipurified, cholesterol-free diet containing 40% carbohydrate can produce aortic sudanophilia or aortic atherosclerosis in vervet monkeys (Cercopithecus aethiops pygerethrus) depending on the particular carbohydrate fed. Four groups of vervet monkeys (three males and three females per group) were fed semipurified diets containing lactose. Two of the groups were also fed 15% cellulose (C) or 15% cellulose plus 0.1% cholesterol (CC); the two other groups were fed 15% pectin (P) or 15% pectin plus 0.1% cholesterol (PC). The average serum total cholesterol and low density lipoprotein cholesterol levels over the entire feeding period (mg/dl +/- SEM) were, for C, 156 +/- 14 and 95 +/- 5; for P, 173 +/- 15 and 112 +/- 8; for CC, 187 +/- 27 and 122 +/- 21; and for PC, 155 +/- 11 and 108 +/- 7. Cholesterol levels at autopsy (mg/dl +/- SEM) were, for C, 103 +/- 6; for P, 108 +/- 16; for CC, 92 +/- 9; and for PC, 106 +/- 7. Aortic sudanophilia (percentage of area) was, for C, 5.9 +/- 2.7; for P, 13.5 +/- 9.4; for CC, 5.3 +/- 2.1; and for PC, 21.6 +/- 10.3. Dietary pectin led to more severe sudanophilia (increased by 129% in the absence of cholesterol and by 308% in its presence) than did cellulose. Analysis of aortic glycosaminoglycans (GAG) revealed that dermatan sulfate levels fell in both cholesterol-fed groups, and chondroitin sulfate fell in aortas of group CC. Heparan sulfate levels were unaffected by cholesterol feeding. Hexuronic acid, galactosamine and hexosamine levels were elevated in the pectin-fed monkeys, but levels were unaffected by dietary cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of dietary fiber on lipids and aortic composition of vervet monkeys. 301 55

Vinculin- and caldesmon-immunoreactive forms and actin isoform patterns were studied in samples of normal and atherosclerotic human aorta. After removal of adventitia and endothelium, the remaining tissue was divided into three layers: media, muscular-elastic (adjacent to media) intima, and subendothelial (juxtaluminal) intima. In media of normal aorta, meta-vinculin accounted for 41.0 +/- 0.9% (mean +/- SEM) of total immunoreactive vinculin (meta-vinculin + vinculin); 150-kDa caldesmon accounted for 78.2 +/- 5.1% of immunoreactive caldesmon (150-kDa + 70-kDa); the fractional contents of alpha-smooth muscle actin, beta-nonmuscle, and gamma-isoactins were 49.0 +/- 0.6%, 30.4 +/- 0.6%, and 20.8 +/- 0.8%, respectively. Muscular-elastic intima was very similar to media by these criteria. In subendothelial intima, the fractional content of meta-vinculin and 150-kDa caldesmon was significantly lower (6.9 +/- 1.5% and 32.7 +/- 7.0%, respectively) than in muscular-elastic intima and media, whereas the isoactin pattern was identical to that in adjacent layers, demonstrating the smooth muscle origin of subendothelial intima cells. In atherosclerotic fibrous plaque, the fractional content of alpha-actin was decreased in subendothelial intima, rather than in media and muscular-elastic intima. Additionally, the proportion of subendothelial intima cells [i.e., the cells that express low amounts of smooth muscle phenotype markers (meta-vinculin, 150-kDa caldesmon, and alpha-actin)] in the total intima cell population increased dramatically in atherosclerotic fibrous plaque. The results suggest that changes in the relative content of meta-vinculin and 150-kDa caldesmon as well as alpha-actin in human aortic intima are associated with atherosclerosis although, in subendothelial intima of normal aorta, a certain smooth muscle cell population exists that expresses reduced amounts of "contractile" phenotype markers, even in the absence of the disease.
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PMID:Modulation of human aorta smooth muscle cell phenotype: a study of muscle-specific variants of vinculin, caldesmon, and actin expression. 314 99

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.
Atherosclerosis 1988 Aug
PMID:Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis. 314 45

1. Cholesterol feeding of rabbits impairs the endothelium-dependent relaxation (EDR) evoked by acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon. 2. Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2% cholesterol and other lipids for 4 weeks. Age-matched control animals were fed a standard rabbit diet. The concentrations of cholesterol and triglycerides in plasma were measured and the extent of atherosclerosis was estimated by staining the aortae with Sudan Red. Light and electron microscopy were undertaken also. 3. Rings of aorta were prepared for recording isometric tension. They were contracted with noradrenaline (NA) and EDR elicited by adding ACh. 4. The young rabbits showed weight gain, hypercholesterolaemia, prominent Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of cholesterol-induced atherosclerosis. The older animals showed significant weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of atherosclerosis. The SEM appearances were similar to the young animals fed cholesterol. 5. EDR to ACh was significantly impaired in both groups of cholesterol-fed rabbits. The maximal relaxations to ACh in young control and cholesterol-fed rabbits were 46.4 +/- 2.9% and 24.0 +/- 4.3% (mean +/- s.e. mean, n = 8, P less than 0.05) of the contractile response to NA (1 mumol 1(-1]. The corresponding results in the age control and cholesterol-fed rabbits were 31.8 +/- 3.9% and 9.1 +/- 1.5% (n = 9, P less than 0.05). 6. The young rabbits were far more susceptible to cholesterol-induced atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of atherosclerosis although hypercholesterolaemia was present.
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PMID:Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit. 326 Aug 4

Our personal experience on the application of scanning electron microscopy in cardiology, gastroenterology and ophthalmology is reviewed. SEM has not yet significantly contributed to myocardium pathology. However, in the near future, SEM could be a reliable technique to complete the information available from other sources. As to atherosclerosis, SEM allowed us to improve our knowledge of the early stages of the disease; some pathological features, not always detected by conventional morphological examinations, can be documented. An important contribution to gastrointestinal pathology was made by SEM investigations both in the staging of some important diseases (i.e., coeliac disease, peptic ulcer, Crohn's disease, ulcerative colitis) and in the follow-up of mucosal changes during therapy. In the ophthalmological field, SEM provided three-dimensional new information to clinicians, who are familiar with the biomicroscopic images. Our experience in hematology is still limited. However, in the last few years SEM joined to immunocytochemistry allowed us to characterize cell populations in several blood diseases. Some procedures of particular interest in the management of human bioptic specimens are stressed in order to get to a complete correlative microscopy. We conclude that continuous and simultaneous correlations have to be carried out between SEM and other methods and instruments available for morphological investigation.
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PMID:Scanning electron microscopy application in clinical research. 332 26


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