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)

[3H]Trioleyl glyceryl ether and [3H]cholesteryl linoleyl ether were bound to Intralipid and injected intraperitoneally into mice. About 20% of the injected label was recovered from peritoneal macrophages up to 2 weeks after injection, and there was a gradual appearance of the label in the liver. Following injection of acetylated low density lipoprotein, labeled with [3H]trioleyl glyceryl ether, into rats, about 90% of the label appeared in the liver shortly after injection and all label was retained up to 73 days. The findings indicate that [3H]cholesteryl linoleyl ether and [3H]trioleyl glycerol can serve as non-degradable analogs of atheroma lipids, which are readily taken up by macrophages when presented in the form of appropriate substrates. These preliminary results serve as basis for experiments designed to study the role of macrophages in the transport of atheroma lipids.
Atherosclerosis 1982 May
PMID:Long-lived labeling of phagocytic cells with analogs of atheroma lipids. 709 76

Patterns of triacylglycerol (TG) turnover in plasma and liver, and the hepatic secretion of very density lipoprotein triacylglycerol (VLDL TG) into the circulation, have been studied in young Large White female pigs, using i.v. tracer [1,3-14C]- and [2-3H]glycerol. Serial measurements were made of plasma [14C]glycerol and [14C]glucose and of liver TG and plasma VLDL TG specific activities. In other studies VLDL TG obtained from a donor pig was reinjected into recipient animals to measure the early disappearance (dilution) of VLDL TG. Multicompartmental analysis revealed a mean rate of hepatic TG turnover somewhat slower than the rate of VLDL TG turnover, suggesting that almost all of the hepatic TG turnover was due to secretion of VLDL TG, and that the intestine probably contributed an appreciable part of the newly synthesized plasma VLDL TG. The t1/2 of reinjected VLDL TG, whether prepared by the most rapid possible techniques and reinjected immediately or stored for several days, was approximately 10 min. This was much faster than the t1/2 of the falling limb of the plasma VLDL TG curve seen after injection of labelled glycerol (t1/2 approximately 2 H). Thus, in these respects, the pig resembled all other species studied rather than human subjects as described by Farquhar et al.
Atherosclerosis 1980 Sep
PMID:Very low density lipoprotein metabolism in domestic pigs. 742 88

Diabetes mellitus is associated with typical patterns of long term vascular complications which vary with the organ involved. The microvascular kidney disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the capillary basement membranes and increased deposition of extracellular matrix components (ECM), while loss of microvessels with subsequent neovascularisation is predominant in the eye and peripheral nerves. On the other hand macrovascular disease is characterized by accelerated atherosclerosis. These complications are dependent on long term hyperglycemia. Specific biochemical pathways linking hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988), glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven 1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop, 1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the synthesis of growth factors particularly since atherosclerosis and angioneogenesis are associated with increased proliferation of endothelial and smooth muscle cells. Increased synthesis of ECM components is stimulated by growth factors like transforming growth factor beta (TGF beta) (Derynck et al., 1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review will summarize some of the recent evidence for an involvement of growth factors in diabetic vascular complications and will attempt to assign their emergence in the sequence of events leading to vascular complications.
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PMID:Diabetic microvascular complications and growth factors. 762 Nov 7

We previously reported that oleic acid (OA) rapidly increased apolipoprotein (apo) B secretion by suppressing early intracellular degradation of nascent apo B in Hep G2 cells and suggested that the suppression of apo B degradation is associated with triglyceride (TG) biosynthesis from OA. To determine whether the inhibition of apo B degradation is associated with increased TG synthesis or is a direct effect of OA, we examined the effect of another fatty acid, eicosapentoenoic acid (EPA), on apo B kinetics in Hep G2 cells, since it is well known to have hypolipidemic action in clinical studies. The incorporation of [3H]glycerol into cellular TG was stimulated five-fold when Hep G2 cells were incubated for 2 h with EPA or OA (0.4 or 0.8 mM-1.5% bovine serum albumin (BSA) complex). The incorporation of [14C]acetic acid into cellular cholesteryl ester (CE) was significantly decreased by EPA treatment, whereas OA did not affect CE synthesis. Similar effects of these fatty acids on cellular lipid synthesis were observed in long-term incubation (24 h). Apo B was linearly secreted into the medium during 3 h, and EPA and OA doubled the rate of secretion. In long-term (24 h) incubations, both fatty acids significantly increased the incorporation of [3H]leucine into secreted apo B radioactivity or the accumulation of apo B mass in the medium. Pulse-chase studies revealed that both EPA and OA reduced intracellular apo B degradation to a similar degree. The inhibition of apo B degradation was also observed when the cells were preincubated with either EPA or OA for 24 h. These results suggest that increased TG synthesis leads to suppression of intracellular apo B degradation, which is independent of the source of exogenous fatty acid.
Atherosclerosis 1995 Jan 06
PMID:Similar to oleic acid, eicosapentaenoic acid stimulates apolipoprotein B secretion by inhibiting its intracellular degradation in Hep G2 cells. 777 67

Previous investigations have used 13C-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that 13C-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was < 40%, and in group B, OR was > 40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19, C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)n, the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)n, and PUFA/(CH2)n ratios are markers of fatty acid saturation. (C19, C21)/(CH2)n, choline/(CH2)n, and glycerol/(CH2)n are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15 +/- 0.34 versus 1.63 +/- 0.32 in group B (P = .005). PUFA/(CH2)n is 0.26 +/- 0.10 in group A versus 0.16 +/- 0.04 in group B (P = .049). C19, C21/(CH2)n in group A is 0.32 +/- 0.15 versus 0.63 +/- 0.23 for group B (P = .003). No significant difference was found in UFA/(CH2)n or in the TG or PL ratios. 13C spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction.
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PMID:13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction. 798 Nov 85

Macrophage scavenger receptors, which have been implicated in the development of atherosclerosis and other macrophage-mediated events, are trimeric integral membrane glycoproteins whose extracellular domains have been predicted to include alpha-helical coiled-coil, collagenous and globular structures. To elucidate further the structural and functional properties of these receptors, we generated transfected Chinese hamster ovary cells which express secreted extracellular domains of the type I and type II bovine scavenger receptors and developed a solid-phase bead-binding assay to assess their ligand-binding properties. The secreted receptors exhibited the distinctive high-affinity, broad polyanionic ligand-binding specificity and the pH dependence of binding which characterize the membrane-anchored cell-surface forms of the receptors. Both the type I and type II secreted receptors were trimeric glycoproteins comprising disulfide-linked dimers and noncovalently associated monomers. Gel filtration and glycerol-gradient centrifugation established that the type II trimers were highly elongated and did not associate into higher order oligomers at the low concentrations used in these experiments. Crocilodite asbestos, which is phagocytosed by alveolar macrophages and can cause asbestosis and mesothelioma, bound efficiently to secreted type I receptors and less well to the type II receptors. This binding was specific in that it was competed by a variety of well established scavenger receptor ligands but not by negative controls. These studies have identified a new type of insoluble scavenger receptor ligand, and have raised the possibility that scavenger receptors may play a role in mediating the physiological and pathological interactions of inspired particles with alveolar macrophages.
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PMID:Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos. 838 34

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent Diabetes Mellitus (IDDM), HL activity and the characteristics of LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of LDL in treated IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were classified by the WHO criteria, were free of nephropathy and hypothyroidism, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The IDDM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values > or = 4.3 and IDDM-B (n = 6) with HL < or = than 4.2 mumoles glycerol/ml h. the HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and TG were assayed. LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in IDDM than in C (p < 0.05) (Table 2), although average values DMID not exceed the reference values of 200 mg/dl. The TG-LDL were higher in IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of IDDM-B, whose plasma concentrations of TG-LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in IDDM-A (p < 0.02). (Table 3). The chemical composition of LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.05), a lower percentage of cholesterol than IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2% (p < 0.05) and also a larger percentage of proteins than IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0% (p < 0.01). The correlations between TG/cholesterol and HL activity in IDDM were r = -0.53 (p < 0.05) and in IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the LDL particle in IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that LDL is an indisoluble association of lipids and apoproteins, and that both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LDL rich in TG and poor in cholesterol, shows low affinity for LDL receptors in human fibroblasts. Also in IDDM the interaction of LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of LDL, for the normalization of the TG/cholesterol relation and for the conformation of typical LDL particles.
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PMID:[Low density lipoprotein rich in triglycerides and hepatic lipase activity in insulin-dependent diabetic patients]. 872 71

Oxidative modification of low density lipoprotein (LDL) is known to be a key event for induction of atherosclerosis. However, there has been little progress in structural elucidation of oxidized lipids, especially oxidatively fragmented phospholipids retaining a glycerol backbone. In this study, we found that LDL derived from egg yolk has no platelet-activating factor (PAF) acetylhydrolase activity, and that prolonged incubation of egg yolk LDL with Cu2+ resulted in the formation of various PAF-like lipids: 1-acyl type phosphatidylcholines with an sn-2-short-chain dicarboxylate or monocarboxylate group. Only a very small amount of the PAF-like lipid having an sn-2-short-chain monocarboxylate group was detected by gas chromatography-mass spectrometry in Cu(2+)-oxidized LDL from human plasma with high PAF-acetylhydrolase activity, which has been reported to hydrolyze PAF-like lipids to lysophosphatidyl-cholines. Preincubation of plasma LDL with diisopropyl fluorophosphate dose-dependently inhibited PAF-acetylhydrolase activity, resulting in accumulation of the PAF-like lipids when the LDL was oxidized with Cu2+. As well as PAF and lysophosphatidylcholines, several PAF-like lipids were found to inhibit [3H]thymidine incorporation into cultured vascular smooth muscle cells derived from rat aorta. The possible formation of PAF-like lipids by lipid peroxidation in LDL is discussed as well as its possible significance for induction of atherosclerosis.
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PMID:Lipid peroxidation in low density lipoproteins from human plasma and egg yolk promotes accumulation of 1-acyl analogues of platelet-activating factor-like lipids. 897 57

Control of apolipoprotein B (apo B) secretion in hepatocytes occurs partly at the post-translational level. The key step in this process appears to be intracellular degradation of newly synthesized apo B. The aim of this paper was to investigate the mechanisms that regulate apo B secretion by Hep G2 cells, in response to the inhibition of Acyl-CoA Acyltransferase (ACAT) by the compound Sandoz 58035 (S-58035). S-58035 (20 microM) reduced cholesteryl ester synthesis from [14C]oleate by 95%, and increased significantly, in a dose-dependent manner, (2-100 microM) apo B secretion, either in control conditions (from 78 +/- 4.3 to 126 +/- 6.1 ng apo B-100/mg cell protein/4 h) or upon stimulation of apo B secretion by oleate (from 134 +/- 4.23 to 177 +/- 4.3 ng apo B/mg cell protein/4 h). This increased secretion of newly synthesized apo B-100 was confirmed by pulse experiments and by gradient ultracentrifugation of the media. Moreover pulse-chase experiments showed that the addition of S-58035 reduced intracellular degradation of apo B-100, both in control conditions and in the presence of oleate. S-58035 (20 microM) did not affect total cellular cholesterol content, but free cholesterol increased with a concomitant decrease of cholesteryl ester (-20%). S-58035 increased cellular triglyceride mass, which was observed in basal conditions (from 12.8 +/- 1.09 to 22.7 +/- 2.7 micrograms TG/mg cellular protein) and also in presence of oleate (from 48 +/- 0.53 to 59 +/- 6.3 micrograms TG/mg cellular protein). This effect is due to a stimulation of triglyceride synthesis, as determined by incorporation of [3H]glycerol into cellular triglycerides. From these data we conclude that, under our experimental conditions, triglyceride synthesis and/or availability is likely to control intracellular degradation of apo B.
Atherosclerosis 1997 Apr
PMID:Decreased intracellular degradation and increased secretion of apo B-100 in Hep G2 cells after inhibition of cholesteryl ester synthesis. 912 58

We report a 62-year-old man who developed coma and died in a fulminant course. The patient was well until May 1, 1996 when he noted chillness, tenderness in his shoulders, and he went to bed without having his lunch and dinner. In the early morning of May 2, his families found him unresponsive and snoring; he was brought into the ER of our hospital. He had histories of hypertension, gout, and hyperlipidemia since 42 years of the age. On admission, his blood pressure was 120/70, heart rate 102 and regular, and body temperature 36.3 degrees C. His respiration was regular and he was not cyanotic. Low pitch rhonchi was heard in his right lower lung field. Otherwise general physical examination was unremarkable. Neurologic examination revealed that he was somnolent and he was only able to respond to simple questions such as opening eyes and grasping the examiner's hand, but he was unable to respond verbally. The optic discs were flat; the right pupil was slightly larger than the left, but both reacted to light. He showed ptosis on the left side, conjugate deviation of eyes to the left, and right facial paresis. The oculocephalic response and the corneal reflex were present. His right extremities were paralyzed and did not respond to pain Deep tendon reflexes were exaggerated on the right side and the plantar response was extensor on the right. No meningeal signs were present. Laboratory examination revealed the following abnormalities; WBC 18,400/ml, GOT 131 IU/l GPT 50 IU/l, CK616 IU/l, BUN 30 mg/dl, Cr 2.1 mg/ dl, glucose 339 mg/dl, and CRP 27.4 mg/dl. ECG showed sinus tachycardia and ST elevation in II, III and a VF leads and abnormal q waves in I, V5, and V6 leads. Chest X-ray revealed cardiac enlargement but the lung fields were clear. Cranial CT scan revealed low density areas in the left middle cerebral and left posterior cerebral artery territories. The patient was treated with intravenous glycerol infusion and other supportive measures. At 2: 10 AM on May 3, he developed sudden hypotension and cardiopulmonary arrest. He was pronounced dead at 3:45 AM. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had acute myocardial infarction involving the inferior and the true posterior walls and left internal carotid embolism from a mural thrombus. Post mortem examination revealed occlusion of the circumflex branch of the left coronary artery due to atherom plaque rupture and myocardial infarction involving the posterior and the lateral wall with a rupture in the postero-lateral wall. Marked atheromatous changes were seen in the left internal carotid, the middle cerebral and the basilar arteries; the left internal carotid and the middle cerebral arteries were almost occluded by thrombi and blood coagulate. The territories of the left middle cerebral and the occipital arteries were infarcted; but the left thalamic area was spared. The neuropathologist concluded that the infarction was thrombotic origin not an embolic one as the atherosclerotic changes were severe. Cardiac rupture appeared to be the cause of terminal sudden hypotension and cardiopulmonary arrest. It appears likely that a vegetation which had been attached to the aortic valve induced thromboembolic occlusion of the left internal carotid artery which had already been markedly sclerotic by atherosclerosis. It is also possible that the vegetations in the aortic valve came from mural thrombi at the site of acute myocardial infarction, as no bacteria were found in those vegetations.
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PMID:[A 62-year-old man with an acute onset of consciousness disturbances]. 945 48


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