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)

Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experiments demonstrate that the effect of HDL3, and to a lesser extent HDL2, on apoE secretion is specific, concentration-dependent, and may require interaction with the HDL receptor. Very low density lipoproteins (VLDL) and low-density lipoproteins (LDL) fail to specifically stimulate apoE secretion by cholesterol-loaded macrophages. The effect of HLD3 is maximal at 25-50 micrograms/ml (0.26-0.52 microM) and can be totally abolished by mild nitrosylation (with 3 mM tetranitromethane (TNM)). Data are also presented to indicate that the increased rate of apoE secretion in the presence of HDL3 is not due to a "protective" effect of this lipoprotein on possible proteolytic degradation or cellular reuptake of apoE secreted into the media. The stimulatory effect of HDL on apoE secretion can be clearly dissociated from cholesterol efflux; HDL stimulates apoE secretion from oxysterol-treated cells in the absence of measurable cholesterol efflux, while TNM-HDL promotes substantial cholesterol efflux from cholesterol-loaded cells but has no effect on apoE secretion. The kinetics of apoE synthesis and secretion, determined in short-term labeling studies, demonstrate that under all experimental conditions examined a substantial portion of cellular apoE is not secreted. Furthermore, in cholesterol-loaded cells HDL3 increases apoE secretion essentially by diversion of a greater portion of cellular apoE pool for secretion. While HDL3 has no effect on the rate of apoE synthesis, cellular apoE turns over two-fold faster in cells incubated in the presence of HDL3 than in its absence (t 1/2 = 11 +/- 2 and 22 +/- 4 min, respectively), an observation corresponding well with the changes in the rates of apoE secretion under similar conditions. The HDL3-mediated increase in apoE secretion by cholesterol-loaded macrophages suggests another mechanism by which HDL exerts a protective effect in the development of atherosclerosis; increased contribution to the metabolic pool of apoE by peripheral tissues may lead to a more effective clearance of peripheral cholesterol by the liver (reverse cholesterol transport).
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PMID:Regulation of apolipoprotein E secretion by high density lipoprotein 3 in mouse macrophages. 207 40

We studied the lipidic metabolism and the atherogenic risk factors non related to lipidic metabolism in two groups of patients: group 1 with only coronary disease and group 2 with coronary disease and atherosclerosis in the cerebral and/or peripheric artery territories. Patients of group 2 showed a cholesterol, cLDL, and B-apoprotein titers significantly higher than group 1. Systolic and diastolic blood pressure were higher in group two. Also the incidence of diabetes mellitus in group 2 was higher than in group 1. In a stepwise discriminating analysis the diastolic arterial pressure and cholesterol titers were the parameters with a greatest predictive potential for the presence of localized or generalized ischemic disease. B-apoprotein was the lipidic parameter with the greatest predictive potential. All together these data suggest that in coronary patients, a discrete increase in plasma cholesterol can imply a risk of suffering ischemia in some other arterial territories. Diastolic blood pressure, cholesterol and diabetes mellitus are the factors with the highest predictive potential for the generalization of arteriosclerosis.
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PMID:[Factors associated with generalized forms of arteriosclerosis in patients with coronary disease]. 209 Nov 13

Ordinarily, HDL1, a fraction of HDL enriched in apoE, is a minor fraction of plasma, but in human subjects and experimental animals eating diets high in fat and cholesterol and in patients with homozygous familial hypercholesterolemia (HFH) or CETP deficiency, HDL1 (or HDLc) concentrations in plasma are increased. However, little is known about the structures, compositions and metabolic sources of HDL1 in HFH patients. To obtain HDL1 for the study, we surveyed several fractions in the HDL density range for apoE by SDS-PAGE. The ratio of apoE to apoAI in the HDL (d = 1.063-1.21 g/ml) of 8 HFH patients was 0.14 +/- 0.03 compared to 0.03 +/- 0.005 in a control group of 8 normolipidemic subjects (P less than 0.001) suggesting that an apoE-rich fraction indeed was present in increased amounts. ApoE/apoAI ratios of lipoproteins of the density range 1.050-1.090 were even higher at 1.5 and 2.0 in 2 patients compared to 0.4 +/- 0.1 in controls, indicating that this density fraction may be particularly enriched with apoE-rich lipoproteins. By contrast, d = 1.020-1.050 g/ml and d greater than 1.090 fractions contained very little apoE. Therefore, we further characterized the d = 1.050-1.090 g/ml lipoproteins of HFH patients and controls. Fractionation of an d = 1.050-1.090 fraction by concanavalin-A chromatography (CONA) yielded an unbound apoE-rich fraction that contained apoE, apoAI and apoC but no apoB, and a bound LDL-like fraction that contained mostly apoB-100, as determined by SDS-PAGE and by solid phase immunoassays, containing monoclonal antibodies directed against apoB, apoE and apoAI. The apoE/apoAI ratio of the CONA unbound fraction of HFH patients was greater, and the fraction also contained more free cholesterol and phospholipids than the fraction of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1990 Oct
PMID:Apolipoprotein E-rich HDL in patients with homozygous familial hypercholesterolemia. 212 36

Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n = 74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.
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PMID:Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries. 2741 77

Authors determined the plasma levels of total cholesterol, HDL-cholesterol, apoprotein B-100 (apo B-100), apoprotein A-I (apo A-I) and lipoprotein(a) in 202 (139 female and 63 male) randomized blood donors. The phenotypes of lipoprotein(a) were detected by SDS-polyacrylamide gelelectrophoresis and Western blotting. The average plasma total cholesterol concentration of this Hungarian population was 5.7 +/- 1.1 mmol/l. The other lipoprotein parameters were HDL-cholesterol: 1.36 +/- 0.04 mmol/l; and the apoprotein B-100 concentration: 70 +/- 17.4 mg/dl. In these parameters no difference between males and females could be found. The average plasma apoprotein A-I in females was 156.3 +/- 23.6 mg/dl and in males 143.8 +/- 26.8 mg/dl and the difference was statistically significant (p less than 0.01). The average lipoprotein(a) concentration of this population was 10.5 +/- 13.5 mg/dl and there was no significant difference between males and females (9.0 +/- 10.7 and 13.9 +/- 17.7 mg/dl, respectively). The distribution of plasma Lp(a) was highly skewed in the direction of low concentration values. In females a moderate bimodial distribution could be demonstrated. Documented by several authors lipoprotein(a) level higher than 30 mg/dl serves as an independent risk factor for atherosclerosis. In this population only 9.4% of subjects had lipoprotein(a) concentrations over this limit (5.9% female and 3.5% male). The relative alle frequency of different phenotypes showed the following distribution: B 0.007, S1 0.015, S2 0.154, S3 0.231, S4 0.230 and null 0.362. In this population the F phenotype could not be detected.
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PMID:[Plasma concentration of lipoprotein(a) and distribution of its subtypes in the healthy population of Hungary]. 214 42

Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis.
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PMID:Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig. 214 14

The extracellular lipid that accumulates in fibrous atherosclerotic lesions appears to be derived directly from plasma low density lipoprotein (LDL). One factor that may influence the lipid deposition is immobilization of part of the LDL in lesions, and an immobilized fraction can be released by incubation with the fibrinolytic enzyme, plasmin, suggesting that it is associated with fibrin. The lipoprotein variant Lp(a) is associated with increased risk of arterial disease, and its characteristic apoprotein, apo(a), is structurally related to plasminogen, suggesting that it might bind to the plasminogen binding sites on fibrin. In this study we have compared blood Lp(a) and the soluble and plasmin-releasable Lp(a) in 45 samples of normal intima and different types of lesion. Levels of soluble and plasmin-releasable Lp(a) were dependent on both blood level and type of tissue sample. Although the amount of soluble LDL was 5-20 times higher than Lp(a) in intima, the amounts released by plasmin were similar, and Lp(a) appears to account for most of the apo B-containing lipoprotein that is immobilized in lesions.
Atherosclerosis 1990 Oct
PMID:Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein. II. Preferential immobilization of lipoprotein (a) (Lp(a)). 214 68

Among the numerous risk factors for atherosclerosis, 2 are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins. Antihypertensive treatments significantly decrease the risk of cerebrovascular accidents, renal failure or hypertensive cardiomyopathy, but they have little influence on coronary artery disease. It has been suggested that some antihypertensive agents may have deleterious effects by altering serum lipoproteins and this may override the benefit of blood pressure reduction. Diuretics increase the blood concentration of total cholesterol, low-density lipoproteins and triglycerides. Indapamide, a methylindoline agent with vasodilator activity, has no adverse lipid effects. Twenty-six studies have clearly demonstrated that indapamide appears to be unique among diuretics because of an absence of adverse lipid effects. In some studies indapamide significantly increased high-density lipoprotein cholesterol, apoproteins A1, A2 and apoprotein E. When a thiazide diuretic had been given previously, indapamide treatment normalized the lipid and lipoprotein profiles. The reason for the lack of adverse lipid effects of indapamide is discussed. Thus indapamide, 2.5 mg once daily, is effective and safe for the control of mild to moderate hypertension, both in young and older patients. It may be an optimal diuretic for use in normolipidemic or hyperlipidemic patients, as it increases high-density lipoprotein but not low-density lipoprotein cholesterol.
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PMID:Beneficial effects of indapamide on lipoproteins and apoproteins in ambulatory hypertensive patients. 218 57

The effects of boiled coffee (BC) and filtered coffee (FC) on serum lipoproteins were compared in 41 healthy subjects whose serum cholesterol concentration was less than 7 mmol/l. The subjects consumed in random order BC and FC for 4-week periods in a crossover design. The individual daily consumption ranged from 2 to 14 cups (mean 5.7 cups per day) and was similar during both study periods. The serum total and LDL-cholesterol and apoprotein B concentrations were higher (P less than 0.001) and HDL-cholesterol lower (P less than 0.05) after BC than after FC. Bodyweight, apoprotein A-I and triglycerides remained unchanged. In the 16 subjects who consumed coffee less than 5 cups per day the difference in serum total cholesterol between the BC and FC periods was non-significant (P = 0.16). The differences in serum total cholesterol and LDL-cholesterol between the periods showed significant linear correlations with the amount of coffee consumed daily (r = 0.52, P less than 0.001 and r = 0.33, P less than 0.05, respectively) but no association was found between the difference in HDL-cholesterol and the amount of coffee (r = 0.14, P = 0.39). The results indicate a dose-dependent increasing effect on serum total and LDL-cholesterol and apoprotein B concentrations of boiled coffee.
Atherosclerosis 1990 Aug
PMID:Dose-dependent effect on serum cholesterol and apoprotein B concentrations by consumption of boiled, non-filtered coffee. 224 1

Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen-deficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n = 17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n = 20), and 3) continuously administered 17-beta estradiol (n = 18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one-half) in animals in both hormone replacement groups (p less than or equal to 0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subfraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women.
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PMID:Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone. 224 55


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