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

Metabolic intermediate levels, glycolytic and Krebs cycle enzyme activities and lysosomal acid hydrolase activities were measured in aortas of spontaneously hypertensive (SHR) versus normotensive (WKY) rats. In the hypertensive aortas the level of lactate, the ratio of lactate to glucose and of lactate to malate was higher in the SHR than WKY aortas. In the hypertensive aortas the obvious shift of metabolism toward higher rate of glycolysis was associated with decreased activity of malate dehydrogenase and espically of lipoamide dehydrogenase. The latter is an essential compoenent of the alpha-ketoglutarate and pyruvate dehydrogenase enzyme complexes and it appears that these complexes are among the sites of arterialmetavolism which are primarily altered by the elevated blood pressure, resulting in increased production of lactate. The activity of the marker lysosomal enzyme N-acetyl-beta-glucosaminidase was unequivocally elevated in the hypertensive aortas. The activity of beta-glucuronidase exhibited incogruous differences between the SHR and WKY aortas and the activity of aortic acid phosphatase did not differ in the two rat strains. The results are discussed in relation to arterial injury, permeability, and atherogenesis.
Atherosclerosis 1977 Nov
PMID:Metabolic intermediates, enzymes and lysosomal activity in aortas of spontaneously hypertensive rats. 59 42

Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.
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PMID:Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus. 65 43

Two trioleoyl glycerol hydrolases, one of lysosomal origin as determined by a high correlation with the lysosomal marker enzyme, N-acetyl-beta-glucosaminidase, and one having the characteristics of lipoprotein lipase, were measured at varying stages of lesion development in the aortas of cholesterol-fed rabbits. Both lipases were greatly enhanced in atheromatous aortas and were linearly related to lesion severity as measured by total aortic cholesterol. Lipoprotein lipase activities of myocardium and of plasma of cholesterol-fed rabbits were also significantly increased relative to controls. The data suggest that lipoprotein lipase might be a factor regulating cholesterol deposition in the aorta.
Atherosclerosis 1977 Jun
PMID:Effect of cholesterol feeding on arterial lipolytic activity in the rabbit. 90 18

Normal arterial foci which take up Evans blue dye (EBD) in vivo are believed to represent atherosclerosis-prone, hemodynamically stressed foci compared to areas which exclude dye. We have used the rabbit EBD model to examine focal aortic hydrolases of blue areas versus white areas, and we report herein significant focal variations of hydrolase activities. Enzymes measured included neutral alpha-glucosidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, acid alpha-glucosidase, beta-galactosidase, beta-glucuronidase, cathepsin C, and acid cholesteryl esterase (ACE); specific activities were expressed on the basis of tissue DNA. In correlative areas of EBD uptake in normal rabbit aortic arch, ACE activity averaged 17% higher and cathepsin C activity averaged 37% lower than activities of areas free of EBD in the descending thoracic aorta (P less than 0.02). None of the glycosidases studied differed significantly between blue and white aortic areas. These findings indicate that discrete, intrinsic differences of hydrolytic enzyme activities exist in the normal rabbit aorta in areas delineated by in vivo EBD uptake, areas recognized as lesion-prone vs lesion-resistant.
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PMID:Intrinsic focal variations of rabbit aortic hydrolase activities. 276 19

In eight New Zealand white male rabbits the abdominal aorta and one iliofemoral artery was balloon deendothelialized (group A). After 2 weeks they were kept for 6 weeks on a high cholesterol diet together with eight unoperated rabbits (group B). Eight more rabbits were kept on a commercial diet only (group C). The degree of atherosclerosis was much higher in the deendothelialized Group A vessels than in the uninjured group B vessels. The activity of lactate dehydrogenase and of the rate-limiting glycolytic pyruvate kinase was significantly increased and the activity of lipoamide dehydrogenase decreased in the group A aortas. In the iliofemoral arteries a similar but statistically insignificant tendency was detected. There was no significant difference, however, in aortic lactate between the three groups. Thus, local hypoxia did not significantly contribute to the high degree of atherosclerosis in the group A animals in spite of the enzyme activity differences. Previous experience of the authors, using arterial microcathode pO2 measurements, indicates that following deendothelialization an adaptive proliferation of nutrient vessels and increased arterial oxygenation takes place. The average activity of the lysosomal N-acetyl-beta-glucosaminidase was five times and that of beta-glucuronidase, seven times higher in the Group A than Group B aortas; in the iliofemoral arteries the differences were even larger. The huge elevation of these hydrolases, which are involved in glycosaminoglycan catabolism, provides indirect indication that accumulation of glycosaminoglycans and possibly their ability to form complexes with apoB-containing lipoproteins played a major role in the much increased degree of atherosclerotic lesions in the Group A rabbits.
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PMID:The effect of combined deendothelialization and hypercholesterolemia on some arterial lysosomal and glycolytic enzymes and lactate in rabbits. 335 Jan 45

In order to obtain information about the changes in lysosomal enzyme activities in arterial endothelial cells under hypertensive conditions, a biochemical study was performed on 5 lysosomal enzymes, acid phosphatase, N-acetyl-beta-glucosaminidase (NAGase), cathepsin B, cathepsin D and beta-glucuronidase, in endothelial cells isolated by an enzymatic technique from the aorta of spontaneously and renal hypertensive rats, and normotensive control rats. The aortic endothelial cells in the old spontaneously and the renal hypertensive rats showed increased activities of enzymes examined in comparison with those in the age-matched control rats. Endothelial cells in young spontaneously hypertensive rats did not show any elevated enzyme activities compared with those in the controls, and the enzyme activities tended to increase with aging. From this, it is deduced that hypertension activates lysosomal enzyme activities in aortic endothelial cells. The differences in the activities of NAGase, cathepsin B and cathepsin D between hypertensive and control animals increased markedly with advancing age. These activated lysosomal enzymes seem to be involved in the developmental mechanism of arterial endothelial cell injury in hypertension and in further development of hypertensive vascular changes.
Atherosclerosis 1988 Mar
PMID:Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells. 335 16

The development of a model of chronic myocardial ischemic injury (MII) in rabbits by administering increasing doses of isoproterenol (ISO) is described. Repeated s.c. injections of increasing doses of ISO (0.5 mg/kg, on day 1 to 15.5 mg/kg, on day 15) resulted in an increase in serum glucose, free fatty acids and creatine phosphokinase. Examination of hearts from ISO-treated rabbits revealed marked hypertrophy of the left ventricle and an increase in total water content. Biochemical analysis showed an increase in left ventricular hydroxyproline and a decrease in ATP and glycogen content following ISO-treatment. Ion measurements revealed extensive accumulation of Na and Ca, with the Ca being preferentially accumulated in the mitochondria. Measurement of subcellular organelle marker enzymes showed decreases in the sarcolemmal Na+-K+-stimulated (ouabain-sensitive), mitochondrial (azide-sensitive) and sarcoplasmic reticulum ATPase activities in the ISO-treated animals. Analysis of lysosomal enzyme activities in myocardial homogenates showed significant decreases in the latency of N-acetyl-beta-glucosaminidase and cathepsin D. The above biochemical alterations in ISO-induced MII generally parallel changes previously seen in the rabbit following acute coronary artery ligation. The present model allows the study of MII uncomplicated by some uncertainties arising from the surgical or anesthetic procedures employed in acute "open-chest" preparations and would permit long-term follow-up studies of pharmacological interventions. The susceptibility of the rabbit to experimental atherosclerosis should allow the development of an experimental model of MII which more closely approximates the clinical situation.
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PMID:Myocardial ischemic injury induced by isoproterenol in the rabbit: biochemical and chemical alterations. 385 Jul 74

Homogenates of control and diet-induced atherosclerotic aortas of rabbit were prepared and the levels of DNA, protein, free and esterified cholesterol, and six enzymes known to be associated with various subcellular organelles [N-acetyl-beta-glucosaminidase, beta-galactosidase (lysosomes); cytochrome oxidase (mitochondria); neutral alpha-glucosidase (endoplasmic reticulum); 5'-nucleotidase (plasma membrane); catalase (peroxisomes)] were compared between control and atherosclerotic preparations. The levels of prostaglandins I2, E2, and F2 alpha, based on DNA, also were measured by radioimmunoassay. Atherosclerotic aortas were significantly enriched in catalase activity (440%) and in each of the acid hydrolases (395 and 630%), based on DNA, as well as in free (630%) and esterified cholesterol (930%), based on tissue wet weight, compared to control aortas. The control level of prostaglandin I2 was 10-fold higher than that of prostaglandin E2, which was 3-fold higher than that of prostaglandin F 2 alpha. Prostaglandin I2 doubled in amount with advanced atherosclerosis, while prostaglandin E2 increased over 10-fold, resulting in twice the amount of prostaglandin I2 than E2 in advanced atherosclerosis; the level of prostaglandin F2 alpha did not appear to change significantly with atherosclerosis. Increased levels of prostaglandins I2 and E2 were correlated significantly with increased aortic total cholesterol content (based on DNA) but not increased serum cholesterol levels. N-Acetyl-beta-glucosaminidase activity also was correlated significantly to aortic total cholesterol content and beta-galactosidase activity, as well as to the level of prostaglandin I2; in contrast, N-acetyl-beta-glucosaminidase was not significantly correlated to prostaglandin E2. The association of prostaglandins I2 and E2 with aortic total cholesterol suggests the participation of prostaglandins in the response of arterial cells to lipid accumulation in atherosclerosis. The specific association of aortic prostaglandin I2 level and N-acetyl-beta-glucosaminidase activity further suggests a possible role for this prostaglandin during arterial intralysosomal cholesterol accumulation.
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PMID:Arterial prostaglandins and lysosomal function during atherogenesis. I. Homogenates of diet-induced atherosclerotic aortas of rabbit. 389 3

This report validates and expands further the interpretation of our findings on prostaglandins and lysosomes in rabbit aortic homogenates (see paper I of this series) to enzymatically isolated and separated aortic cell populations during atherogenesis. Evidence is provided by which isolated arterial cells may be considered representative of in situ increases of diseased aortic tissue prostaglandin I2 and E2 levels, as well as lysosomal acid hydrolase activities and total cholesterol content based on DNA. Increasing latency of aortic lysosomal N-acetyl-beta-glucosaminidase activity was confirmed and correlated with increasing severity of atherosclerosis, in parallel to increasing levels of prostaglandin I2 but not increasing levels of prostaglandin E2. Ultrastructural observations also confirmed aortic intracellular lipid accumulation within lysosomes and as lipid droplets. Consistent with these relationships, separated low density, lipid-filled aortic cells were especially increased in total (197%) and latent (15%) lysosomal acid hydrolase activities, catalase activity (274%), total cholesterol (151%), and in both prostaglandin I2 (67%) and E2 (325%) levels based on DNA, as compared to control aortic cells or more normal-appearing high-density diseased aortic smooth muscle cells; high-density diseased aortic cells were increased in prostaglandin E2 but similar in latent acid hydrolase activity compared to control aortic cells. Since the total cholesterol content of rabbit atherosclerotic aortas was evidenced more intracellularly (75%) than extracellularly (25%) in this study, the association of increased prostaglandin I2 and E2 levels with low-density lipid-filled cells suggest the participation of these prostaglandins in the genesis of aortic foam cells during arterial lipid accumulation in rabbit atherosclerosis. The association of increasing prostaglandin I2 levels and increasing latent lysosomal N-acetyl-beta-glucosaminidase activities also implicates a possible relationship between this prostaglandin and lysosomal membranes of aortic cells, either primary or secondary to intralysosomal lipid accumulation.
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PMID:Arterial prostaglandins and lysosomal function during atherogenesis. II. Isolated cells of diet-induced atherosclerotic aortas of rabbit. 392 57

Fourteen male rabbits born at elevation 4000 ft (first experimental series) were transferred at age of 2 months to elevation 12470 ft and raised there for 18 weeks. Half of the animals remained on a commercial rabbit chow (group H) while the other half was on the same diet supplemented with cholesterol (group C). Eight male rabbits raised at sea level served as controls (group S). Intima-media homogenates from the thoracic aortas were assayed for lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lipoamide dehydrogenase, pyruvate kinase (PK), phosphofructokinase (PFK) and the lysosomal hydrolases beta-glucuronidase and N-acetyl-beta-glucosaminidase (NAGA). Aortic lactate and glucose were also measured. Thirty-two male rabbits (second experimental series) were subdivided into 4 groups. Rabbits were fed a cholesterol-supplemented diet not only at high altitude (8 rabbits matching group C) but also 8 animals raised at sea level. The degree of atherosclerosis in the aortas of these 4 groups was assessed by measuring the aortic cholesterol contents. Plasma cholesterol was also determined. In the aortas of the rabbits of group H the activity of PK was significantly elevated, and the activity of the lysosomal hydrolases significantly decreased compared with aortas of group S rabbits. There was no difference in the other enzyme activities or in the aortic glucose and lactate content of these groups. Cholesterol feeding of the animals of group C resulted in a significantly increased activity of the lysosomal hydrolases as well as of LDH and PK. The lipid analyses (second experimental series) revealed a trend to a lower concentration of aortic cholesterol in the high altitude than in the sea level animals, both fed a cholesterol diet, in spite of the higher plasma cholesterol concentrations in the high altitude animals. The low aortic lysosomal hydrolase activities in the high altitude rabbits are in accord with their comparatively lower susceptibility to experimental atherosclerosis. This metabolic feature may be due to a lower degree of exposure of these aortas to injurious factors, such as infections or lower blood pressure. The elevated activity of PK without increased lactate content in group H animals seems to parallel the well-known general adaptation of the organism to high altitude hypoxia, and does not indicate a metabolic switch toward anaerobic glycolysis.
Atherosclerosis 1984 Aug
PMID:Aortic enzymes and lactate in high altitude-raised and cholesterol-fed rabbits. 623 25


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