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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol feeding in miniature swine resulted in a hypercholesterolemia with a distinctive hyperlipoproteinemia and the subsequent development of atherosclerosis. Alterations in the type and distribution of plasma lipoproteins induced by cholesterol feeding were as follows: (a) the occurrence of beta-migrating lipoproteins (B-VLDL) as well as very low density lipoproteins in the d less than 1.006 ultracentrifugal fraction; (b) an increased prominence of the intermediate lipoproteins (d = 1.006-1.02); (c) an increased prominence of low density lipoproteins; and (d) the occurrence of a distinctive lipoprotein with alpha mobility which was referred to as HDLc (cholesterol induced). Characterization of the various plasma lipoproteins included chemical composition, size by electron microscopy, and apoprotein content. The B-VLDL resembled the beta-migrating lipoproteins of human Type III hyperlipoproteinemia and contained a prominent protein equivalent to the arginine-rich apoprotein in addition to the B apoprotein, apo-A-I, and the fast-migrating apoproteins (apo-C). The HDLc were rich in cholesterol, ranged in size from 100 to 240 A in diameter, and contained the arginine-rich apoprotein and apo-A0I but lacked the B apoprotein. The arginine-rich apoproteins isolated from B-VLDL and HDLc by gel chromatography were similar in amino acid analyses, with glutamic acid as their amino-terminal residue. The occurrence of a spectrum of cholesterol-rich lipoproteins which contained the arginine-rich apoprotein with the occurrence of accelerated atherosclerosis suggested an interesting, although speculative, association.
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PMID:Swine lipoproteins and atherosclerosis. Changes in the plasma lipoproteins and apoproteins induced by cholesterol feeding. 16 8

Patas monkeys were studied for 2 years on three dietary regimes: (1) commercial chow (control diet); (2) semipurified diet plus lard (fat-fed); and (3) semipurified diet plus lard and cholesterol (cholesterol-fed). The control and fat-fed animals had similar lipoproteins which were equivalent to the human very low density, low density (LDL), and high density lipoproteins. An additional lipoprotein referred to as LDL-II appeared to be equivalent to the human Lp(a). The cholesterol-fed animals developed accelerated atherosclerosis associated with a hypercholesterolemia which was characterized by (1) the appearance of beta-migrating lipoproteins (B=VLDL) in the d less than 1.006, (2) an increase in the intermediate lipoproteins and LDL, and (3) the appearance of LDL-II which contained a prominence of the arginine-rich apoprotein. The arginine-rich apoprotein was also a prominent component of the B-VLDL and intermediate lipoproteins. Characterization of this apoprotein revealed that it contained 11.5 mol % arginine, had a molecular weight of approximately 34 000, and coelectrophoresed with the arginine-rich apoprotein of man, dog, swine, rat, and rabbit.
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PMID:Atherogenic hyperlipoproteinemia induced by cholesterol feeding the Patas monkey. 18

Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies.
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PMID:Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. 19 82

The lipid and apoprotein composition of very low density lipoproteins (VLDL) (d less than 1.019 g/ml) from normal and hypercholesteremic (h.c.) rabbits are compared. Significant changes are observed in the apoproteins, as well as in the fatty acid composition of cholesterol esters, and in the relative distribution of phospholipids. Apoproteins show a marked increase of peptides with slow mobility (R2 and R3), corresponding to arginine-rich proteins, both in the rabbit and in some types of human hyperlipoproteinemias (hypothyroidism and Fredrickson Type III). VLDL were separated into the two fractions, VLDL-1 and VLDL-2. Peptides of slow mobility were shown to be present in a higher concentration in VLDL-1. Cholesterol esters of h.c. VLDL have a very high content of oleic acid, the 18:1/18:2 ratio being about three times higher than in normal VLDL. Phospholipid distribution in h.c. VLDL is characterized by an increase of sphingomyelin and decrease of phosphatidylethanolamine. The PC/Sph ratio is about one fifth that of normal. These changes in VLDL lipids are very similar to those occurring in the lipid composition of the atherosclerotic plaques in mammals.
Atherosclerosis
PMID:Very low density lipoproteins in normal and cholesterol-fed rabbits: lipid and protein composition and metabolism. Part 1. Chemical composition of very low density lipoproteins in rabbits. 23 65

Arginine-induced insulin secretion was evaluated in 13 patients with endogenous hypertriglyceridemia (Fredrickson's Type IV) before and after a two-month period of Clofibrate therapy. Clofibrate reduced triglyceride, cholesterol and FFA levels by 68, 28 and 15% respectively and provoked a significant reduction in arginine-induced insulin secretion without modifying glucose response. Arginine-induced insulin secretion was also studied in 11 normal subjects during saline and intralipid infusions. Glucose and insulin basal values, and glucose and insulin response to arginine infusion were not influenced by Intralipid infusion in these controls. These results confirm that clofibrate reduces insulin secretion thereby contributing to decreased serum triglyceride levels.
Atherosclerosis
PMID:Effects of clofibrate treatment on arginine-induced insulin secretion in endogenous hypertriglyceridemia. 100 8

Human growth hormone (HGH) response to i.v. insulin (0.1 U/kg body weight) and arginine infusion (25 g of L-arginine for 30 min) was studied in 9 patients (5 males and 4 females) with primary familial hypercholesterolaemia and belonging to 4 families. Mean age was 28 +/- 2 years (range 18-36) and body weight was less than 105% of ideal body weight. Glucose tolerance and insulin response to oral glucose were normal in all patients. HGH release after insulin and after arginine was slightly increased as compared to 21 normal controls, but the differences were not significant. Insulin and glucagon response to arginine in these patients was within the normal range. Plasma glucose and free fatty acids were normal after both insulin and arginine. Moreover, no significant correlation was found between fasting cholesterol and HGH peaks after insulin and after arginine, nor between cholesterol and insulin and glucagon responses. Despite marked hyperlipidaemia, HGH-deficient patients examined by other authors never present signs of atherosclerotic disease. Our data suggest that HGH, in the presence of elevated cholesterol levels, might play an important role in the development of atherosclerotic lesions.
Atherosclerosis
PMID:Growth hormone response to insulin and to arginine in patients with familial hypercholesterolaemia. 120 Nov 52

This paper reviews recent developments in the biochemistry, pharmacology and physiology of the L-arginine/nitric oxide pathway. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor (EDRF) and its continuous release plays a crucial role in the regulation of vascular tone and platelet activity. In the nervous system nitric oxide is a neurotransmitter. In the peripheral nervous system, nitroxergic nerves form a part of the non-adrenergic, non-cholinergic innervation of the visceral organs. In the immune system, nitric oxide generated by activated macrophages has tumoricidal and antimicrobial activities. Growing evidence suggests that the alterations in the formation of NO in various tissues contribute to the pathogenesis of various diseases, including hypertension, atherosclerosis, diabetes, subarachnoid hemorrhage and septic shock. Therefore, the improvements in our understanding of the regulation of L-arginine/nitric oxide pathway on the molecular level may lead to the development of new drugs.
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PMID:[Biological role of metabolic pathways from L-arginine to nitric oxide]. 134 93

Vascular responses to intraluminal and abluminal activation of human platelets were examined in carotid arteries from normal and atherosclerotic rabbits. The carotid artery was perfused in vitro, platelets were activated with thrombin (0.1 unit/ml), and changes in diameter were measured. In vessels from normal animals, intraluminal activation of platelets produced dilatation of preconstricted arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5) M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist. Abluminal activation of platelets produced modest constriction in quiescent arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP produced pronounced dilatation of preconstricted arteries. In vessels from atherosclerotic animals, endothelium-dependent dilatation to intraluminal activation of platelets and to ADP was impaired and dilator responses to sodium nitroprusside were normal. These experiments indicate that 1) intraluminal activation of human platelets produces endothelium-dependent dilatation in perfused carotid arteries, whereas abluminal activation of human platelets produces vasoconstriction, which is mediated primarily by serotonin, and 2) atherosclerosis markedly impairs vasodilator responses to activation of human platelets, probably because vasodilatation to ADP released from platelets is impaired.
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PMID:Effect of atherosclerosis on responses of the perfused rabbit carotid artery to human platelets. 139 May 92

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.
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PMID:L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. 140 Oct 62

The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.
Atherosclerosis 1992 Aug
PMID:Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100. 141 96


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