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)

The effect of metoprolol, a beta 1-blocker, on atherogenesis was evaluated in rabbits fed a diet supplemented with 0.25% cholesterol and 3% coconut oil for 21 weeks. After 7 weeks on the diet, the rabbits were randomly divided into treated (n = 22) and untreated (n = 22) groups. Treated animals received metoprolol subcutaneously by an osmotic pump for 14 weeks, resulting in a plasma level of 774 +/- 69 nM during the investigation. Plasma concentrations of cholesterol, triglycerides, and phospholipids did not differ between the two groups. Nor were there any significant differences between the two groups in plasma concentrations of apolipoprotein A-I, apolipoprotein B, apolipoprotein C-III, and apolipoprotein E measured by electroimmunoassay. At the end of the study, the aortas were cut into three portions and the extent of atherosclerosis was determined by morphometry. The group that had received metoprolol had significantly (p less than 0.015) less atherosclerosis in the aorta (ascending plus arch 37.8 +/- 6.8%, thoracic 32.9 +/- 6.1%, abdominal 19.8 +/- 6.1% of total intimal area; mean +/- SEM) than the controls (ascending plus arch 54.9 +/- 7.1%, thoracic 48.0 +/- 6.2%, abdominal 25.9 +/- 5.5%).
 ...
PMID:Effect of metoprolol on diet-induced atherosclerosis in rabbits. 334 91

The goals of this study were to determine whether vasa vasorum in atherosclerotic coronary arteries respond to vasoactive stimuli and to examine effects of regression of atherosclerosis on blood flow through vasa vasorum in coronary arteries. We studied three groups of monkeys: normal, atherosclerotic, and regression. Blood flow to vasa vasorum was measured with microspheres. Blood flow to intima-media (ml/min x 100 g) was 5 +/- 1 (mean +/- SEM) in normal and 47 +/- 7 in atherosclerotic monkeys (p less than 0.05). Infusion of phenylephrine or serotonin did not alter flow through vasa in normal monkeys. In atherosclerotic monkeys, phenylephrine decreased flow through vasa vasorum in intima-media of coronary arteries to 24 +/- 4 (p less than 0.05), and serotonin decreased flow to 27 +/- 5 (p less than 0.05). In regression monkeys, blood flow to intima-media was sixfold less (7 +/- 2 ml/min x 100 g) than in atherosclerotic monkeys (p less than 0.05). During infusion of adenosine, blood flow to vasa was fourfold greater in atherosclerotic monkeys than after regression of atherosclerosis. This finding suggests that loss of vessels, not constriction of existing vessels, accounts for the decrease in flow through vasa in intima-media after regression of atherosclerosis. We conclude that vasa vasorum in atherosclerotic coronary arteries respond to vasoconstrictor stimuli and that there is loss of vasa vasorum and a large decrease in blood flow through vasa to intima-media of coronary arteries after regression of atherosclerosis.
 ...
PMID:Vasa vasorum in atherosclerotic coronary arteries: responses to vasoactive stimuli and regression of atherosclerosis. 334 75

For the study of cholesteryl ester transfer from different plasma lipoproteins into human aortic tissue, patients scheduled for reconstructive aortic surgery were intravenously injected with autologous in vitro labeled lipoproteins 20 to 24 hours before aortic intima-media samples were obtained during the operation. The injectate contained high density lipoproteins (d greater than 1.063) labeled with 3H-cholesteryl ester and lipoproteins of lower density (d less than 1.063) labeled with 14C-cholesteryl ester or lipoproteins with the opposite labeling. In 16 aortic tissue samples (some with visible atherosclerosis) from 11 normocholesterolemic patients, the aortic influx of total cholesteryl ester was 1 to 50 nmol x cm-2 x day-1. Some 39% +/- 3% (mean +/- SEM) of the influx was derived from high density lipoproteins, which in plasma accounted for only 22% +/- 2% (mean +/- SEM) of the esterified cholesterol. The findings suggest that: 1) esterified cholesterol from the two lipoprotein fractions in plasma enter the aortic intima by the same mechanism, and 2) influx of cholesteryl ester from the smaller, high density lipoproteins is greater than influx from the larger, lower density lipoproteins considering their concentrations in plasma. In some patients, the cholesterol content in the intima-media tissue with no visible atherosclerosis corresponded to only a few months of continuous cholesteryl ester influx. This time is short considering the age of the patients and, therefore, indicates that removal of esterified cholesterol from the intima-media is of major importance in preventing cholesterol deposition in the arterial wall.
 ...
PMID:In vivo transfer of cholesteryl ester from high and low density plasma lipoproteins into human aortic tissue. 337 21

The effect of bezafibrate (BZF) on plasma fibrinogen levels has been studied in 62 patients with atherosclerotic vasculopathy and hyperfibrinogenemia (643 +/- 15 (SEM) mg/dl). In a preliminary study, 15-30 days of BZF therapy (400-600 mg/day) normalized fibrinogen values in 16 subjects were compared to 16 controls. The effect was rapid and dose-dependent, and discontinuation in 6 patients who could not complete the study was followed by a rebound increase. A controlled study with 400 mg/day in the other 24 patients for 15 days showed that BZF lowered fibrinogen, PF4, blood filterability and platelet aggregating thresholds to the normal range. BTG and FpA decreased significantly compared to the placebo group (12 and 12 patients randomly distributed) without any variation in potentially biassing hematologic values (WBC, PLTS, Ht, lipids and plasma glucose). BZF may be of value in chronic treatment of hyperfibrinogenemia in atherosclerotic patients with a view to improving the haemorheologic pattern and, hence, reducing activation of the coagulation pathway.
Atherosclerosis 1988 Jun
PMID:Effect of short-term treatment with bezafibrate on plasma fibrinogen, fibrinopeptide A, platelet activation and blood filterability in atherosclerotic hyperfibrinogenemic patients. 340 Dec 84

The metabolism of infused 111In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t1/2) for clearance of 111In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits (means +/- SEM; n = 4). By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue stores. Disappearance of excess plasma cholesterol was greater than 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative gamma camera imaging, hepatic trapping of 111In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance, acquiring 22.0% +/- 1.7% (WHHL) and 16.8% +/- 1.0% (normal of total 111In. Aortic uptake of 111In was less than 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, our results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia.
 ...
PMID:Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis. 342 21

Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocyte-derived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19 +/- 1.19 vs 6.11 +/- 0.94 nmol/mg cell protein/20 h, mean +/- SEM, p less than 0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p less than 0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p less than 0.01) and correlated significantly with cholesteryl ester synthesis (r = 0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from type 1 (insulin-dependent) diabetic patients: the influence of non-enzymatic glycosylation of low-density lipoproteins. 343 88

It has recently become possible to measure the in vivo flux of cholesteryl ester from plasma into human aortic tissue by use of labeled cholesterol in patients undergoing reconstructive aortic surgery. For the ascending thoracic aorta without visible atherosclerotic lesions the influx was 4.5 +/- 1.4 nmol X cm-2 X day-1 (means +/- SEM, n = 9). For the abdominal aorta with severe atherosclerosis the influx of cholesteryl ester was 45 +/- 5 nmol X cm-2 X day-1 (n = 12). In both types of tissues the influx of cholesteryl ester from HDL was 2-3 times higher than the influx of cholesteryl ester from LDL and VLDL compared with the concentration of these fractions in plasma. This is in accordance with an aortic influx-mechanism which depends on the sizes and the concentration of the lipoproteins in plasma. The transfer of plasma lipoproteins into human aortic tissue shows a number of similarities with the transfer of plasma lipoproteins into the aortic wall of cholesterol-fed rabbits and also with the transfer of other plasma macromolecules across various capillaries. The cholesterol content in intima-media tissue without lesions corresponded in some of the patients to less than one year of continuous influx of cholesteryl ester from plasma. This time is short compared with the age of the patients. It suggests that removal of cholesterol from the aortic wall represents a major importance in prevention of cholesterol accumulation in that tissue.
 ...
PMID:In vivo transfer of cholesterol from plasma into human aortic tissue. 347 70

The authors sought to determine if isoflurane would attenuate effects of three different types of vasoconstrictors on isolated segments of canine epicardial coronary arteries removed from healthy dogs. As the endothelium has a major role in regulating epicardial coronary artery tone, and as it modulates the effect of many vasoactive substances, experiments were conducted both on normal rings and on rings whose endothelium had been mechanically removed. In addition, the endothelium is thought to be damaged in human atherosclerosis. Rings were suspected in organ chambers filled with modified Krebs-Ringer bicarbonate solution, aerated with 95% oxygen and 5% carbon dioxide, and connected to strain gauges for the measurement of isometric tension. Isoflurane 2.3% (1.5 MAC in the dog) was added to the aerating gas mixture in half the preparations, while the other rings served as control. The vasoconstrictors serotonin, phenylephrine, or prostaglandin F2 alpha were added in increasing concentrations to the bath solution. In the presence of endothelium, vasoconstrictor evoked contractions were attenuated by isoflurane. Maximal tension generated by prostaglandin F2 alpha in untreated rings was 114 +/- 18% (mean +/- SEM) of a reference contraction, while, following isoflurane, it was 46 +/- 8% (P less than 0.005). In the absence of endothelium, isoflurane attenuated neither prostaglandin F2 alpha nor serotonin evoked contraction, and had decreased effectiveness against phenylephrine mediated contraction (P less than 0.001). It is concluded that isoflurane attenuates vasoconstrictor-evoked contraction of isolated canine epicardial coronary arteries, and that this effect is mediated by the endothelium.
 ...
PMID:Isoflurane causes endothelium-dependent inhibition of contractile responses of canine coronary arteries. 366 80

Postmortem studies suggest that coronary angiography does not always accurately delineate the extent of coronary-artery disease. We examined this problem in living human hearts by performing high-frequency epicardial echocardiography at the time of cardiac surgery. The ratio of the diameter of the lumen of the coronary artery to the thickness of its wall was used to quantify the severity of coronary lesions. In 11 patients with no angiographic evidence of coronary disease anywhere in the coronary tree, the mean (+/- SEM) ratio was 5.9 +/- 0.3. In 21 patients with angiographic disease at the site evaluated by echocardiography, the mean ratio was lower (2.3 +/- 0.2, P less than 0.05), reflecting encroachment into the arterial lumen by atherosclerotic plaque. In 15 patients with arterial segments that were angiographically normal but with arterial stenoses elsewhere in the coronary tree, the mean ratio was 4.1 +/- 0.3, with marked overlap with the values in the patients who had angiographic disease at the site of the echocardiographic evaluation. These results demonstrate, in living human hearts, that diffuse coronary atherosclerosis is often present when coronary angiography reveals only discrete stenoses. This finding suggests that coronary angiography may underestimate the severity and extent of coronary disease.
 ...
PMID:Delineation of the extent of coronary atherosclerosis by high-frequency epicardial echocardiography. 380 62

Studies in animals with normal coronary arteries have shown that coronary flow reserve can be predicted by angiographic measurements of arterial stenosis. Studies in man, however, suggest that even quantitative analysis of coronary angiograms cannot predict the physiologic significance of individual coronary lesions. These studies, however, were carried out in patients with either widespread, diffuse coronary artery disease or by measurement techniques that tend to underestimate maximal coronary flow reserve. To determine the relationship between coronary arterial stenosis and coronary flow reserve (CFR) in patients with discrete limited coronary atherosclerosis, we studied 50 patients with a single discrete coronary stenosis in only one or two vessels. The minimum coronary arterial cross-sectional area (mCSA), percent area stenosis (%AS), and percent diameter stenosis in the left and right anterior oblique projections were determined by the Brown/Dodge method of quantitative coronary angiography. A No. 3F coronary Doppler catheter was placed immediately proximal to the lesion. Measurements of CFR were obtained by intracoronary administration of papaverine in doses sufficient to provide maximal arteriolar vasodilation. In 25 patients, a translesional pressure gradient was obtained with an angioplasty catheter. CFR measured in patients with coronary artery disease was compared with that in 13 patients with normal coronary vessels. In normal patients, CFR averaged 5.0 +/- 0.6 (peak/resting velocity ratio; mean +/- SEM, range 3.7 to 8.2). In patients with limited coronary artery disease, CFR was closely correlated with %AS (r = .85), mCSA (r = .79), and the translesional pressure gradient (r = .83). Additionally, the most severe percent diameter stenosis in either the left or right anterior oblique view was also highly correlated with CFR (r = .82). Importantly, all arteries with lesions producing less than 70% area stenosis and less than 50% diameter stenosis, or with greater than 2.5 mm2 mCSA had CFR of over 3.5. These results suggest that, in contrast to the poor correlation of percent area and percent diameter stenosis to CFR measured in patients with multivessel coronary artery disease, CFR measured at angiography in patients with discrete, limited coronary artery disease correlates closely with luminal stenosis determined precisely with quantitative coronary angiography. Differences in the extent of diffuse arterial narrowing may account for these discrepancies.
 ...
PMID:Prediction of the physiologic significance of coronary arterial lesions by quantitative lesion geometry in patients with limited coronary artery disease. 382 34


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