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)

As the intrinsic susceptibility to atherosclerosis differs among several taxonomic groups, the present studies were conducted to compare the angiotoxic responses of atherosclerosis-susceptible (quail) and -resistant (rat) animals to allylamine, a selective cardiovascular toxin. Japanese quail (125-150 g) and Sprague-Dawley rats (175-200 g) were gavaged daily for 1, 7, or 20 d with allylamine HCl (0.7, 7, and 70 mg/kg) or tap water. At the ultrastructural level, subchronic exposure of quail and rats to allylamine was associated with dose- and time-dependent disruption of the structural integrity of aortas. These alterations correlated with fluctuations in the nonprotein thiol content of avian and rodent vessels. Angiotoxicity was not associated with alterations in serum cholesterol content. At all times and doses tested, quail were more susceptible than rats to the angiotoxic effects of allylamine. Although the avian sensitivity to toxic insult was greater than that of rodents, quail aortic homogenates bioactivated allylamine to a lesser extent than rat homogenates. Collectively, these results suggest that the aortic sensitivity to toxic insult in avian and rodent species correlates with their intrinsic susceptibility to vascular injury.
 ...
PMID:Comparative angiotoxic responses of avian and rodent species in vivo: implications in atherogenesis. 232 52

Dietary marine oil supplements may protect against atherosclerosis, although their influence on plasma lipids, in vivo cholesterol metabolism, and aortic cholesterol accumulation remains uncertain. The effects of daily administration of marine oil--delivering 100 mg of eicosapentaenoic acid, 59 mg of docosahexaenoic acid, and 221 mg of omega-3 fatty acids per kilogram--were assessed in 33 New Zealand white rabbits. Six animals (group I) were immediately killed. In the remaining animals stable hypercholesterolemia was induced with a 0.25% cholesterol-enriched diet. After 7 weeks on this diet, six animals were killed (group II). Total plasma cholesterol had increased significantly (982 +/- 119 mg/dl vs. 55.6 +/- 7.1 mg/dl, mean +/- SEM, p less than 0.001). The remaining animals randomly received a tap-water placebo (group III, n = 12) or marine oil (group IV, n = 9) daily. After 3 months, total plasma cholesterol was similar (p = NS) among group II (982 +/- 119 mg/dl), group III (965 +/- 54 mg/dl), and group IV (913 +/- 46 mg/dl). No significant differences in HDL cholesterol, LDL cholesterol, VLDL cholesterol, or triglyceride levels developed between the placebo and marine oil groups. Two-hour, hepatic total lipid, neutral steroid, fatty acid, bile acid, and cholesterol synthesis rates were not significantly affected by marine oil treatment. Thoracic aortic cholesterol content increased during cholesterol feeding (5.7 +/- 0.9 mg/gm vs. 1.1 +/- 0.05 mg/gm, group II vs. group I, p less than 0.05). Marine oil supplementation had no effect on the progressive accumulation of cholesterol in the thoracic aorta (28.8 +/- 2.5 mg/gm vs. 29.4 +/- 1.8 mg/gm, group IV vs. group III, p = 0.84). The abdominal aortic cholesterol contents were also similar. These results do not support the use of dietary marine oil supplements for the amelioration of lipid metabolism or the prevention of atherosclerosis.
 ...
PMID:Dietary marine oil supplements fail to affect cholesterol metabolism or inhibit atherosclerosis in rabbits with diet-induced hypercholesterolemia. 276 25

The aim of present experiment was to investigate the decalcified effects of exogenous elastase in liver, kidney and central nervous system (CNS) of rabbits with atherosclerosis experimentally induced by the modified procedure of Kritchevsky et al. Twenty five male rabbits, weighing approximately 2 kg, were divided into 6 groups. Animals were fed for 3 months with standard diet (group A), standard diet containing 1.5% cholesterol (group B) and 1.5% cholesterol-rich diet plus intraperitoneal (ip) daily administration of elastase 450 EL. U/kg (group C). Another groups were kept for 6 months with standard diet (group D), standard diet containing 0.67% cholesterol (group E) and 0.67% cholesterol-rich diet plus same dose of elastase (group F). The rabbits treated with cholesterol-rich diet were confirmed to be induced atherosclerosis biochemically as well as histologically. All groups were maintained under these conditions for experimental periods and allowed tap water. After 3 and 6 months, blood collected by cardiocentesis using ether anesthesia and then sacrificed to remove CNS and internal organs. Blood had stood for 1 hour at room temperature. Serum was separated by centrifugation at 3,000 rpm for 10 min to determine total cholesterol, triglyceride, phospholipids, HDL-cholesterol, and so on. Calcium contents in the cerebral frontal lobe, cerebellum, pons, spinal cord, liver and kidney were measured by neutron activation analysis method. In this experiment the amelioration of atherosclerosis by ip administration of elastase was ascertained. In rabbits given cholesterol-rich diet, calcium content in CNS tissues was higher than that of another tissues and paralleled to a rise of serum cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The inhibitory effect of elastase on calcium increase in brain and spinal cord of rabbits with atherosclerosis induced by cholesterol-rich diet]. 280 33

The purpose of this investigation was to determine changes in the flow field due to mild atherosclerosis using a main coronary artery casting of man with maximum obstruction of about 50% by area. Local pressure changes were measured using six pressure tap holes drilled flush to the wall along the casting. The test fluid used was a 33% sugar-water solution to simulate the viscosity of blood. Flow visualization results were obtained by injecting blue dye slowly through the pressure tap holes. The local pressure measurements clearly demonstrated a significant Reynolds number effect. At physiological Reynolds numbers of 80-710, a local pressure rise was observed downstream of the mild atherosclerotic constriction of 50% because of momentum changes. The flow visualization study indicated that the critical Reynolds number for flow separation to occur in the divergent region of this coronary casting was about 330. Flow separation has been implicated in the genesis of atherosclerosis but there is little information on the extent of flow separations in vivo in arteries of man. These results are believed to be important in obtaining a quantitative relation between coronary morphology and the fluid dynamic consequences of mild diffuse disease especially under conditions of maximum cardiac demand i.e., higher coronary flow rates, and thus Reynolds numbers associated with space and/or atmospheric flight.
 ...
PMID:Effect of simulated hyperemia on the flow field in a mildly atherosclerotic coronary artery casting of man. 398

The effects of skim milk powder (SMP) and fluid skim milk (FSM) on plasma cholesterol (CH) and hepatic liquid concentrations, and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase activity of rats of different ages were compared. Groups of young (23 days old) and older (45 days old) rats were fed a casein -based diet and provided tap water; the casein-based diet and FSM as fluid source; or tap water and the casein diet into which SMP (25% by wt.) had been isocalorically incorporated. Plasma CH concentrations were determined at 0, 1.5, 3 and 5 wk, hepatic total lipid, triglyceride and CH at 5 wk. Half of each group were killed at wk 3 and the other half at wk 5 for determinations of HMG CoA reductase activity. Both FSM and SMP decreased plasma CH levels at 1.5 and 3 wk of feeding in the young rats; plasma CH concentrations of the older rats were not altered by either FSM or SMP. Both milk derivatives increased HMG CoA reductase activity at wk 3 and wk 5 in both ages of rat, whereas hepatic lipid levels were unchanged. In these experiments the effects of feeding FSM of SMP along with a casein-based diet were comparable and included an increase in HMB CoA reductase activity, no change in hepatic lipid levels, and a decrease in plasma CH; the latter response depended on the initial age of the rat.
Atherosclerosis 1981 May
PMID:Plasma and hepatic cholesterol and hepatic HMG CoA reductase levels in rats fed fluid or powdered skim milk. 724 1

Heparin inhibits smooth muscle cell proliferation in vitro, a property that makes it potentially useful in preventing restenosis after angioplasty. Its utility in this setting is limited by the inability to use high doses (secondary to anticoagulant effects) and the need for subcutaneous administration. We tested the ability of beta-cyclodextrin tetradecasulfate (CDT), a nonanticoagulant synthetic heparin mimic, to inhibit smooth muscle cell proliferation in vitro and tested its efficacy when orally administered for the prevention of angioplasty restenosis in a rabbit atherosclerosis model. Vascular smooth muscle cells were cultured from rabbit aortas by the explant technique. Passaged cells were plated at low density in microtiter plates in the presence or absence of varying concentrations of heparin or CDT in culture medium containing 10% fetal calf serum. Using both 3H-thymidine incorporation and total protein assays, both heparin and CDT caused a similar dose-dependent inhibition of proliferation. We next tested the effect of orally administered CDT in the prevention of restenosis in focal femoral artery arteriosclerotic lesions created in hypercholesterolemic New Zealand White rabbits by air-dessication endothelial injury and subsequent peripheral angioplasty. Animals were followed up for 1 month and were fed normal chow supplemented by tap water with or without CDT. In animals receiving the highest concentration of CDT (2 mg/mL drinking water), the percentage of arterial cross-sectional area with intimal hyperplasia decreased from 50.5 +/- 1.7% (control) to 26.9 +/- 2.2% (p < 0.001), with the intimal/medial ratio being decreased from 1.4 +/- 0.4 to 0.5 +/- 0.2 (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of smooth muscle cell proliferation and experimental angioplasty restenosis by beta-cyclodextrin tetradecasulfate. 849 13

Alpha-tocopherol plays an important role as a lipid-soluble antioxidant. It is present in all major mammalian cell types and shows tissue-specific distribution. This suggests the presence of specific proteins involved in intracellular distribution or metabolism of alpha-tocopherol. A diminution of tocopherol plasma concentrations contributes to the development of diseases such as vitamin E deficiency (AVED), atherosclerosis, and prostate cancer. Further evidence has been obtained for the existence of sites in cellular metabolism and signal transduction where alpha-tocopherol potentially plays a regulatory role. A signal transduction modulation specific for alpha-tocopherol has been described in several model systems. Using radioactively labeled alpha-tocopherol as tracer, we have isolated a new alpha-tocopherol-associated protein (TAP) from bovine liver. This protein has a molecular mass of 46 kDa and an isoelectric point of 8.1. From its partial amino acid sequence, a human gene has been identified with high homology to the newly described protein. Sequence analysis has established that the new TAP has structural motifs suggesting its belonging to a family of hydrophobic ligand-binding proteins (RALBP, CRALBP, alpha-TTP, SEC 14, PTN 9, RSEC 45). Human TAP has been cloned into Escherichia coli, and its tissue-specific expression has been assessed by Northern blot analysis.
 ...
PMID:Identification of a novel cytosolic tocopherol-binding protein: structure, specificity, and tissue distribution. 1079 15

Hyperhomocysteinemia (HH) is an independent risk factor for atherosclerosis, including peripheral arterial occlusive disease (PAOD). Because angiogenesis and collateral vessel formation are important self-salvage mechanisms for ischemic PAOD, we examined whether HH modulates angiogenesis in vivo in a rat model of hindlimb ischemia. Rats were divided into 3 groups: the control group was given tap water, the HH group was given water containing L-methionine (1 g x kg(-1) x d(-1)), and the HH+L-arg group was given water containing methionine (1 g x kg(-1) x d(-1)) and l-arginine (2.25 vol%). At day 14 of the dietary modifications, the left femoral artery and vein were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 4 weeks. Plasma homocysteine levels significantly increased (P:<0.001), and plasma and tissue contents of nitrite+nitrate as well as tissue cGMP levels significantly decreased in the HH group compared with the control group (P:<0.01). Laser Doppler blood flowmetry (LDBF) revealed a significant decrease in the ischemic/normal limb LDBF ratio in the HH group at days 7, 14, 21, and 28 (P:<0.01 versus control). Angiography revealed a significant decrease in the angiographic score in the HH group at day 14 (P:<0.001 versus control). Immunohistochemistry of ischemic tissue sections showed a significant reduction in the capillary density in the HH group (P:<0. 001 versus control). Oral l-arginine supplementation in rats with HH (HH+L-arg) restored the decreased plasma and tissue nitrite+nitrate and cGMP contents (P:<0.05) as well as angiogenesis, as assessed by LDBF (P:<0.05 versus HH), angiographic score (P:<0.01 versus HH), and capillary density (P:<0.001 versus HH). In summary, HH impaired ischemia-induced angiogenesis and collateral vessel formation in a rat model of hindlimb ischemia in vivo. The mechanism of the HH-induced impairment of angiogenesis might be mediated in part by a reduced bioactivity of endogenous NO in the HH state.
 ...
PMID:Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. 1111 56

Epidemiological studies indicate that dietary magnesium influences atherogenesis. Magnesium inhibits plaque formation in animals receiving a high cholesterol diet, whereas the effect of magnesium in animals on low-fat diet has not been explored. Magnesium sulfate was given in the drinking water (50 mg/mL) to 7-week-old apolipoprotein E-deficient (apoE(-)(/)(-)) mice (n=30). Control animals (n=30) received tap water. At the age of 19 weeks, the extent of atherosclerosis and the density of macrophages were measured in the aortic root, and blood lipids were analyzed. The median plaque area was significantly smaller in magnesium-treated female apoE(-)(/)(-) mice and reached only 66% of control females (P<0.02). Plaque area was also less extensive in magnesium-treated male mice, although not statistically significant. Macrophage density was similar in both groups. Magnesium significantly reduced cholesterol (P<0.05) and triglyceride (P<0.01) levels, whereas high density lipoprotein cholesterol remained stable. No significant differences in body and heart weight were seen between treatment groups for either sex. In conclusion, in apoE(-)(/)(-) mice receiving a low-fat diet, magnesium supplementation significantly inhibited atherogenesis in females but not males. Plaque composition remained unchanged in terms of macrophage density. This was obtained in association with significantly reduced levels of cholesterol and triglycerides.
 ...
PMID:Oral magnesium supplementation induces favorable antiatherogenic changes in ApoE-deficient mice. 1134 87

Pravastatin is useful in restoring endothelium-dependent relaxation in hypercholesterolemic animals. A single intravenous bolus injection of N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthase, causes myocardial necrosis and reduces coronary flow in rats. Since rats do not develop hypercholesterolemia and atherosclerosis, we have tested the hypothesis that pravastatin protects the heart from myocardial lesions induced by L-NAME in the absence of alterations in cholesterol levels and plaque formation. Male Wistar rats fed standard chow were divided into four groups: CONTROL (n=14) - rats that received tap water alone for 18 days; L-NAME (n=14) -- rats that received L-NAME (15 mg/kg, i.v.) on the 14th day of the study; PRAVASTATIN (n=11) -- rats that received pravastatin (6 mg/kg/day) in their drinking water for 18 days; PRAVASTATIN+L-NAME (n=12) -- rats that received pravastatin (6 mg/kg/day) and L-NAME (15 mg/kg, i.v.) as indicated in the preceding groups. At the end of 18 days, the rats were sacrificed and the hearts removed for stereological analysis by light microscopy. Plasma nitrate/nitrite and thromboxane B(2) concentrations were determined immediately before and after L-NAME administration. Pravastatin prevented the ischemic lesions induced by the acute inhibition of NO biosynthesis (the area of myocardial lesions in the L-NAME group was greater than in the Pravastatin+L-NAME group: 101.6 microm(2) vs. 1.2 microm(2), respectively; P<0.0001) and markedly increased the plasma nitrate/nitrate concentrations, even before L-NAME administration. There were no significant changes in the plasma thromboxane B(2) concentrations.
 ...
PMID:Pravastatin reduces myocardial lesions induced by acute inhibition of nitric oxide biosynthesis in normocholesterolemic rats. 1146 44


1 2 3 Next >>