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)

Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar.
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PMID:Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis. 141 50

Probucol is a drug that lowers plasma cholesterol in both humans and animals. In low density lipoprotein (LDL) receptor-deficient Watanabe rabbits, probucol reduces the progression of atherosclerosis. This effect may be attributed to the antioxidant and/or the cholesterol-lowering properties of the drug. In the present report we studied the antiatherogenic effect of a probucol analogue (MDL 29,311) that possesses antioxidant activity but that does not lower cholesterol. Modified Watanabe rabbits (11-12 weeks of age) produced by crossing British Brown and Japanese Watanabe rabbits were fed normal chow (n = 8), chow containing 1% probucol (n = 9), or chow containing 0.1% (n = 9), 0.5% (n = 8), or 1% (n = 6) probucol analogue. After 70 days serum cholesterol levels and the percent area of sudanophilic lesions in the thoracic region of aortas were determined. Total serum cholesterol was significantly lowered (p less than 0.05) in the probucol group (560 +/- 54 mg/dl) compared with that of controls receiving no drug (731 +/- 67 mg/dl) but was not lowered in the analogue groups (722-802 mg/dl). The lesioned area (mean% +/- SEM) in the probucol group (16 +/- 3) was significantly lower (p less than 0.01) than in the controls (52 +/- 8). There were 43 +/- 7%, 33 +/- 8%, and 35 +/- 5% of lesions for the 0.1%, 0.5%, and 1% analogue groups, respectively. After combining the data for the 0.5% and 1% analogue groups, the value (34%) was lower than that of the controls and almost reached significance (p = 0.066). The mean serum drug concentration in the 1% probucol group was 58 +/- 4 micrograms/ml compared with 13 +/- 2, 44 +/- 8, and 74 +/- 8 micrograms/ml for the 0.1%, 0.5%, and 1% analogue groups, respectively. Thus, the decreased effectiveness of the probucol analogue in preventing atherosclerosis could not be explained by a lack of bioavailability. LDLs isolated from rabbits treated with the drug were resistant to Cu(2+)-induced lipid peroxidation, as determined by thiobarbituric acid-reactive substances. The resistance within the analogue groups was dependent on the number of antioxidant molecules per LDL particle. However, there was no significant difference in atherosclerotic lesions between these two groups, suggesting, although not definitively, that the maximal antiatherogenic effect had been reached. Our data suggest that the antioxidant activity of this class of compounds may play an important role in reducing atherosclerosis, but not in reducing cholesterol levels, and that hypocholesterolemic and possibly other activities of probucol might further enhance its antiatherogenic activity.
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PMID:Attenuation of atherosclerosis in a modified strain of hypercholesterolemic Watanabe rabbits with use of a probucol analogue (MDL 29,311) that does not lower serum cholesterol. 191 12

We examined the effect of isocaloric substitution of dietary fish oil for lard on the properties of low density lipoproteins (LDL) important in binding to arterial proteoglycans (PG). Cynomolgus monkeys (n = 10) were fed atherogenic diets enriched in fish oil or lard in a crossover study consisting of two 15-week phases of atherogenic diet separated by a 6-week monkey chow "wash-out period." LDL were isolated from plasma during each dietary phase, characterized for chemical and physical properties, and assessed for their ability to interact in vitro with arterial PG. Plasma LDL cholesterol was similar during fish oil and lard consumption (356 +/- 34 and 331 +/- 17 mg/dl, mean +/- SEM), but during fish-oil feeding relative to that of lard, LDL size was smaller (4.2 +/- 0.1 versus 4.9 +/- 0.1 g/mumol) and LDL particles differed in chemical composition. When animals were fed fish oil, significantly fewer (p less than 0.05) LDL particles bound to PG in both dietary phases: 1.00 +/- 0.27 (x10(12)) versus 5.31 +/- 0.83 (x10(12)) particles/micrograms PG in phase 1 and 3.56 +/- 0.67 (x10(12)) versus 6.00 +/- 0.52 (x10(12)) in phase 2 for LDL from animals fed fish oil and lard, respectively. These studies indicate that dietary fat-induced changes in LDL particles lead to altered in vitro interactions with artery wall PG and suggest a novel mechanism for the protective effect of fish oil against atherosclerosis.
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PMID:Reduced proteoglycan binding of low density lipoproteins from monkeys (Macaca fascicularis) fed a fish oil versus lard diet. 193 79

A cDNA clone containing the coding region for cynomolgus monkey cholesteryl ester transfer protein (CETP) was isolated by the polymerase chain reaction with primers based on the human CETP cDNA sequence and cDNA synthesized from liver poly (A+) RNA. Analysis of that cDNA indicated that the nucleotide and amino acid sequences of cynomolgus monkey CETP were greater than 95% homologous with the human sequences. A fragment of the cDNA was used to develop an internal-standard/RNAse protection assay that allowed precise quantification of CETP mRNA levels. Analysis of total RNA from various tissues with this assay revealed that the liver and thoracic aorta expressed high levels of CETP mRNA; the mesenteric fat, adrenal gland, spleen, and abdominal aorta had low but detectable levels of the mRNA; and the brain, kidney, intestine, and skeletal muscle had undetectable levels of that mRNA. When the monkeys were made hypercholesterolemic by a high-fat, high-cholesterol (HFHC) diet, hepatic levels of CETP mRNA increased from 1.6 +/- 0.4 pg/micrograms total RNA (mean +/- SEM) to 4.1 +/- 0.8 pg/micrograms (p less than 0.005); mesenteric fat CETP mRNA increased from 0.4 +/- 0.1 pg/micrograms total RNA to 5.3 +/- 2.2 pg/micrograms (p less than 0.05); and plasma CET activity increased approximately fourfold. The CETP mRNA levels in the thoracic and abdominal aortas were not significantly increased in monkeys fed the HFHC diet, even though those animals had gross atherosclerosis. The apoprotein E mRNA levels, however, were markedly increased in the aortas of monkeys with atherosclerosis, with the largest increase occurring in the abdominal aorta. Taken together, these data suggest that lipid deposition in the artery was not accompanied by increased expression of the CETP gene in that tissue. Statistical analysis showed that a strong, negative correlation existed between hepatic CETP mRNA levels and both high density lipoprotein cholesterol (r = -0.85, p less than 0.001) and apoprotein A-I (r = -0.84, p less than 0.001). These data suggest that HFHC diet-induced changes in high density lipoprotein metabolism may be linked to altered expression of a function CETP gene.
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PMID:Molecular cloning, sequence, and expression of cynomolgus monkey cholesteryl ester transfer protein. Inverse correlation between hepatic cholesteryl ester transfer protein mRNA levels and plasma high density lipoprotein levels. 193 78

Endothelial characteristics and the macrophage foam cell nature of early naturally occurring lesions in the aorta and coronaries of the pigeon have been well characterized. However, the characteristics of pigeon atherosclerosis at other vascular sites have not been extensively studied. The present study was designed to compare atherosclerosis in the brachiocephalic artery with that in the coronaries and aorta. Forty-six White Carneau (WC) pigeons (26 female, 20 male) ranging in age from 2.5 to 7 years were necropsied after fixation under deep anesthesia by perfusion at 160 mm Hg with buffered glutaraldehyde. Arteries stained with Sudan IV for gross evaluation were subsequently processed for SEM and TEM. The occurrence of sudanophilia in the proximal brachiocephalic artery was greater in females (22/26) than in male (2/20). The endothelium, as studied by SEM, was intact over all normal and sudanophilic areas. Cell morphology varied with location in the vessel and gradually changed from polygonally shaped cells with prominent margins and protruding nuclei in the proximal brachiocephalic artery to elongated, flattened cells in distal regions. These regional differences were consistently observed, and did not correlate with age, gender, or areas of lipid accumulation. Unlike lesions in the coronary arteries and at the celiac bifurcation of the aorta, a relative paucity of white blood cells over diffuse sudanophilic areas was observed. This lack of adherent monocytes correlated with lesion ultrastructure. Connective tissue in the intima of the sudanophilic brachiocephalic arteries was disorganized, reflecting both an increase in matrix components and the presence of massive pools of extracellular lipid. Intracellular lipid was minimal and when present was confined to random droplets in the cytoplasm of intimal smooth muscle cells. Monocyte-derived foam cells, characteristic to other vascular beds, were absent from the brachiocephalic artery lesions. These results document differential lesion composition in the WC pigeons and suggest a gender-related susceptibility for brachiocephalic artery atherosclerosis in pigeons.
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PMID:Morphologic characteristics of naturally occurring atherosclerosis in the brachiocephalic artery of the pigeon. 202 38

The goal of this study was to test the hypothesis that atherosclerosis alters responses of cerebral arteries and the ocular circulation to the activation in vivo of leukocytes and platelets. We measured blood flow to the brain and eye using microspheres and pressure in the cerebral microvessels of normal and atherosclerotic monkeys. The intracarotid injection of 10(-7) M N-formyl-L-methionyl-L-leucyl-L-phenylalanine to activate leukocytes did not alter cerebral blood flow in 11 normal or 10 atherosclerotic monkeys but increased the resistance of large cerebral arteries by 46 +/- 11% (mean +/- SEM) in the atherosclerotic animals. The injection of N-formyl-L-methionyl-L-leucyl-L-phenylalanine did not alter blood flow to the eye in 10 normal monkeys but decreased blood flow to the choroid by 38 +/- 9% in 11 atherosclerotic monkeys. The intracarotid injection of 3 x 10(-9) M prostaglandin E2, a leukocyte product, produced an increase in the resistance of large cerebral arteries in five atherosclerotic but not in six normal monkeys. Prostaglandin E2 reduced blood flow to the retina and choroid in the atherosclerotic monkeys by 62 +/- 22% and 65 +/- 17%, respectively. The intracarotid infusion of 25 micrograms/min collagen to activate platelets increased cerebral blood flow by 21 +/- 5% in 10 normal monkeys but did not alter it in 11 atherosclerotic monkeys. Collagen did not alter blood flow to the choroid in 10 normal monkeys but decreased it by 29 +/- 8% in 11 atherosclerotic monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of atherosclerosis on cerebral vascular responses to activation of leukocytes and platelets in monkeys. 205 80

Atherosclerosis is more common and severe in DM. The purpose of this study was to compare the blood lipids profile and the prevalence of different coronary risk factors (CRF) in a mexican population with CHD (coronary heart disease) and DM compared with non DM patients. All had a history of myocardial infarction. Patients with nephropathy or other secondary causes of dyslipidema were excluded. There were two groups of 45 patients, 32 males, 13 females; age was 60 +/- 1 (SEM), body mass index (BMI) 26 +/- 6. Diabetes duration was 10 +/- 1 years. Diabetic individuals referred smoking in 58%, high blood pressure 55%, obesity (IQ greater than 27) 42%. There were no statistical differences with the non DM group. The mean values of total cholesterol, LDL cholesterol and triglycerides were similar in diabetics and non diabetics. HDL cholesterol was significantly lower in diabetic females (p less than 0.01). Hypoalphalipoproteinemia (HDL-C less than or equal to 30 mg/dL) was the most common abnormality in both groups (52% DM vs 38% nonDM) (p less than 0.01) Type IV phenotype was present in 40 vs 29% (NS). Lipid values were not related to BMI, metabolic control or diabetes type of treatment. To conclude, non insulin dependent diabetic patients with CHD have a high prevalence of CRF. Lipid abnormalities, particularly hypoalphalipoproteinemia and hypertriglyceridemia, could be a cause for the increased atherogenic risk, particularly in females.
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PMID:[Diabetes mellitus and ischemic cardiopathy: their relation to changes in plasma lipids and other coronary risk factors]. 209 Nov 76

A new breed of swine, the Yucatan microswine, that was derived from repetitive inbreeding of selected, small Yucatan swine, was investigated as an animal model of advanced vascular atherosclerosis. Nineteen animals were fed an atherogenic diet for 9.9 +/- 1.5 (mean +/- SEM) weeks before and 19.9 +/- 1.8 weeks after balloon endothelial denudation of all four iliac arteries. In 18 (94.7%) of the 19 microswine, angiography performed at 33 to 87 weeks of age disclosed some degree of luminal diameter narrowing: six animals (33.3%) had one-vessel, six (33.3%) had two-vessel, four (22.2%) had three-vessel, and two (11.1%) had four-vessel disease. In 38 (50%) of 76 denuded arteries, angiographically apparent luminal diameter narrowing was observed as follows: three arteries (7.9%) were narrowed less than 50%; 10 arteries (26.3%) were narrowed 50% to 75%; seven arteries (18.4%) were narrowed 76% to 99%; and 18 arteries (47.3%) were occluded. Sixty-four arteries were harvested from 16 of the 18 microswine with angiographically apparent luminal narrowing, which yielded 748 histologic sections. Maximum cross-sectional area narrowing from atherosclerotic plaque exceeded 90% in 135 (18%) of the sections examined, while 65 sections (9%) were narrowed 76% to 90%, and 127 sections (17%) were narrowed 51% to 75%. Atherosclerotic plaque in these animals appeared histologically similar to the so-called "complex" lesion that is typical of human atherosclerosis, which consists predominantly of collagen with focal calcific deposits and a minor lipid component. The smaller size and lower weight of these animals, in comparison with full-size farm pigs and "minipigs," facilitated transportation, handling, and instrumentation. These findings establish the Yucatan microswine as a useful, representative, and economical atherosclerotic animal model for the evaluation of novel interventional techniques.
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PMID:Atherosclerotic Yucatan microswine: an animal model with high-grade, fibrocalcific, nonfatty lesions suitable for testing catheter-based interventions. 230 Dec 18

Pentoxifylline is a methylxanthine derivative used to increase blood flow in peripheral atherosclerosis. Pentoxifylline is known to increase whole blood filtration rate, and recent evidence suggests that pentoxifylline increases the filtration rate of polymorphonuclear leukocytes (PMNs). The purpose of this study was to directly observe and quantitate the effect of pentoxifylline on the flow of individual PMNs into a model capillary. Short-term incubation of human PMNs with 10 mM pentoxifylline inhibited cell activation, as judged by a significant reduction in the number of neutrophils forming pseudopods. Furthermore, incubation of PMNs from 6 healthy men with 0.1, 1.0 and 10 mM pentoxifylline significantly decreased the time required for individual cells to be aspirated into a 4 microns pipet under constant pressure by 16 +/- 5%, 21 +/- 7%, and 41 +/- 8%, respectively (mean +/- SEM, p less than or equal to 0.05), compared with control. These experiments are the first direct demonstration of increased deformability in neutrophils treated with pentoxifylline. The results are consistent with the hypothesis that the beneficial effect of pentoxifylline on microvascular perfusion is partly due to an inhibition of PMN stiffness and activation.
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PMID:Effect of pentoxifylline on the flow of polymorphonuclear leukocytes through a model capillary. 233 24

Small (Sf 20-100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 +/- 1.3% (mean +/- SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 less than d less than 1.063 kg/l) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.
Atherosclerosis 1990 May
PMID:Abnormalities of composition and of in vitro lipolysis products of human small very low density lipoproteins in hypertriglyceridemia. 236 Sep 14


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