Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which women in the reproductive age group are protected from developing coronary heart disease (CHD) as compared with men of similar age is not known. To elucidate whether there is a gender difference in the rate of atherosclerosis formation, we investigated the rate of development of atherosclerosis in both male and female rabbits fed an identical diet consisting of 2% cholesterol for 10 and 15 weeks. The extent of atherosclerosis was correlated with the amount of basal and stimulated release of nitric oxide (NO) from endothelium-intact aortic rings obtained from these animals. Under identical dietary conditions, the female rabbits fed a high cholesterol diet (HCD) for 10 weeks developed very little atherosclerosis (10% surface involvement) as compared with male rabbits (42% surface involvement). However, no significant gender differences in atherosclerosis were observed after 15 weeks of the HCD. The serum cholesterol, high and low density lipoprotein (HDL and LDL) cholesterol were similar in animals fed the HCD for 10 and 15 weeks. The basal release of NO from endothelium-intact aortic rings was significantly greater in control females as compared with males. The magnitude of endothelium-dependent relaxation of aortic rings obtained from both male and female rabbits fed the HCD were impaired to a similar extent, and this impairment correlated with the duration of hyperlipidemia but not with the extent of atherosclerosis. The arginine content of aortic rings were not different between males (257 +/- 52 nmol/g wet weight) and females (345 +/- 62 nmol/g wet weight) or between control and hyperlipidemic groups (males 312 +/- 69; females 301 +/- 65 nmol/g wet weight). Although the precise mechanism for the slower rate of development of atherosclerosis in the female rabbits as compared with males is not clear, the greater basal release of NO in females before they were fed a hyperlipidemic diet, as well as other factors, may be involved. The impairment of endothelium-dependent relaxation in hyperlipidemic animals is not due to a decrease in the availability of arginine, the substrate for NO.
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PMID:Gender differences in atherosclerosis: possible role of nitric oxide. 863 95

Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.
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PMID:Low-density lipoprotein suppresses cathepsins B and L activity in rat mesangial cells. 867 24

Type III hyperlipoproteinaemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (arg-158-->Cys). We identified a 46-year-old white female with severe hyperlipidaemia and the heterozygous apo E3/2* phenotype. Typical clinical characteristics of type III HLP, i.e. palmar xanthomas (orange-yellowish discolorations of the palmar creases) and tuberoeruptive xanthomas, were present in the patient. Without therapy the patient's serum triglycerides (1.098 mg dL(-1)), cholesterol (546 mg dL(-1)), very low-density lipoprotein (VLDL) cholesterol (372 mg dL(-1)) and the apo E concentration (25.0 mg dL(-1)) were distinctly elevated as well as her VLDL cholesterol to serum triglyceride (TG) ratio at 0.34 (normal ratio about 0.2). Direct sequencing of polymerase chain reaction (PCR)-amplified segments of the apo epsilon gene identified a thymine for cytosine (C-->T) exchange in the first base of codon 136 that is predictive for a Cys (TGC) for Arg (CGC) substitution in the encoded amino acid sequence. Two children, an 18-year-old female with the heterozygous apo E4/2* phenotype, a 25-year-old female with the heterozygous apo E3/2* phenotype and the 73-year-old father of the proband with the heterozygous apo E3/2* phenotype are also carriers of the rare mutant. The father has severe atherosclerosis and lipid values compatible with the diagnosis of type III HLP. The affected children have hyper/dyslipidaemia but as yet no clinical expression of the disease. We propose that in the analysed family this rare apo E2 (Arg-136-->Cys) variant is associated with late-onset dominance of type III HLP.
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PMID:Apolipoprotein E2 (Arg-136-->Cys), a variant of apolipoprotein E associated with late-onset dominance of type III hyperlipoproteinaemia. 868 50

The kidneys play an important role in the development of cardiovascular risk factors. It is well known that heavy proteinuria can induce hyperlipidemia, the uric acid is elevated in some renal deficiencies and that hypertension develops in most end stage renal diseases. In prehypertensive states, specially in subjects with a family history of hypertension, some hemodynamic changes take place, characterized by an increase in renal vasoconstriction with a reduction in renal plasma flow and an elevation of sodium reabsorption. The mechanisms for these alterations are not well understood, but an increase in intracytosolic calcium in vascular smooth muscle cells, a reduction in vasodilatory substances such as nitric oxide and an increased sympathetic nervous activity have been proposed. In normotensive subjects with two hypertensive parents a reduction in sodium diet, an increase in protein intake or in arginine diet could prevent established essential hypertension from developing. In borderline hypertension an early therapy with low doses of calcium antagonists, ACE inhibition or diuretics could be indicated.
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PMID:Can the kidney prevent cardiovascular diseases? 874 38

The authors report their experience regarding the identification of Apo-E alleles on atheroma carotid plaques in 20 patients of both sexes diagnosed as suffering from severe carotid stenosis using Doppler tests. A DNA hybridization and amplification method was used to identify Apo E-2, Apo E-3 and Apo E-4 alleles and their various phenotypical combinations. The following results were obtained in the 20 plaques examined: Apo E-3/E-4 in 114 patients (70%), 2 diabetic patients Apo E-4/E-3, one vascular demented patient Apo E-2/E-3, and 3 plaques defined as severely calcified Apo E-2/E-2. It can therefore be seen that the majority of plaques (70%), considered a risk for future stroke due to altered carotid Doppler tests, does not differ greatly by the homozygote allele Apo E-3/E-3 commonly found in the blood of the so-called "normal" population. It is difficult to draw any conclusions from the alleles found in the other 5 patients due to their scarce statistical value and the limited number of carotid plaques examined, but there appears to be some sort of correlation between calcified plaque, hyperlipidemia and the allele Apo E-2/E-2, with an interchange of position between cysteine arginine amino acids in the Apo E sequences.
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PMID:[Atheroma plaque and Apo E alleles]. 876 17

This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholesterol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation.
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PMID:Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation. 885 18

The relaxation of aortic rings in response to acetylcholine (ACh) was significantly decreased in cholesterol-fed mice. The attenuated relaxation in cholesterol-fed mice was preserved by the chronic administration of prazosin (20 mg/kg/day) or pravastatin (12.5 mg/kg/day). Serum low-density lipoprotein (LDL) levels were significantly increased in mice given cholesterol. The increased serum LDL levels in cholesterol-fed mice were returned to normal by the chronic administration of prazosin and pravastatin. A prior incubation of aortic rings with lysophosphatidylcholine (LPC) significantly attenuated ACh- and A23187-induced endothelium-dependent relaxation. The inhibitory effects of LPC on endothelium-dependent relaxation were not affected by indomethacin or superoxide dismutase. The sodium nitroprusside-induced relaxation of aortic rings was not changed by LPC. The inhibitory effects on ACh-induced relaxation by NG-monomethyl-L-arginine were restored by a prior exposure to L-arginine, whereas the inhibition of endothelium-dependent relaxation by LPC was not affected by L-arginine. These results suggest that cholesterol-fed mice are useful animal models of hypercholesterolemia, and chronic administration of prazosin or pravastatin can preserve endothelium-dependent relaxation by lowering serum LDL in these animals. It is further suggested that LPC derived from oxidized LDL may be involved in the reduced endothelium-dependent relaxation in hyperlipidemia.
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PMID:Preservation of endothelium-dependent vascular relaxation in cholesterol-fed mice by the chronic administration of prazosin or pravastatin. 886 52

Low density lipoprotein (LDL) plays an important role in atherogenesis. Focal accumulation within the arterial intima of excess amounts of cholesterol-rich LDL leads to the migration and recruitment of monocytes, which then differentiate into macrophages after taking up large amounts of oxidatively modified LDL via their scavenger receptors and become lipid-laden 'foam cells' within the subendothelial space. It is generally accepted that oxidized LDL and hyperlipidaemia impair endothelial-dependent vascular relaxation, yet the existing literature on the effects of oxidatively modified LDL on endothelium-derived nitric oxide (NO) and prostacyclin (PGI2) release is inconclusive, since oxidized LDL has been reported to enhance or reduce NO and PGI2 production. Our studies using cultured human endothelial and smooth muscle cells have established that basal rates of L-arginine (NO precursor) transport, NO and PGI2 production and soluble guanylyl cyclase activity are unaffected by pretreatment (for 1 or 24 h) with native LDL, or with mildly or highly oxidized LDL. In contrast, highly oxidized LDL inhibited histamine-stimulated release of NO and PGI2 from human endothelial cells and induced an adaptive increase in the level of intracellular glutathione in human smooth muscle cells, a response which was prevented by the chain-breaking antioxidant alpha-tocopherol. Although initial rates of L-arginine transport and basal NO and PGI2 release from human endothelium are unaffected by oxidized LDL, agonist-stimulated release of these vasodilators is markedly attenuated. Elucidation of the mechanisms regulating these responses and their sensitivity to dietary antioxidants could lead to alternative strategies for reducing atherogenesis.
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PMID:Modulation of vascular tone by low density lipoproteins: effects on L-arginine transport and nitric oxide synthesis. 912 49

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

A 49 year-old hypercholesterolemic male with marked electrocardiographic ST segment depression on exercise testing was found to have an apo E E3/3 phenotype by isoelectric focusing, but an APOE E4/3 genotype using HhaI restriction isotyping. DNA sequence analysis of the proband's APOE gene found a G-->C point mutation at codon 251. This predicted a change in the amino acid encoded by codon 251, from arginine to glycine. The mutation occurred on an allele that encoded arginine at position 112 and this variant was named APOE R112; R251G. The R251G change altered a recognition site for the endonuclease StuI and was the basis for a restriction isotyping method to rapidly screen for this mutation. In relatives of the proband, APOE R112; R251G was consistently found in subjects with both hyperlipidemia and atherosclerosis. Apo E R112; R251G-containing very low density lipoproteins bound normally to macrophages in vitro. However, the proband had an abnormal post-prandial lipoprotein response to a dietary fat challenge. The association of APOE R112; R251G with abnormal phenotypes suggests that the amino acid change in the carboxy-terminal, perhaps in combination with the common amino acid polymorphism at codon 112, has a functional impact upon lipoprotein metabolism in members of this family.
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PMID:Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease. 936 Jun 38


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