Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fatty acid composition of phospholipids and triglycerides in heart muscle was examined in normal and alloxan-diabetic male Wistar rats. In diabetes the major phospholipids, phosphatidyl choline and phosphatidyl ethanolamine, showed significant changes in fatty acid composition, whereas cardiolipin and phosphatidyl serine + phosphatidyl inositol did not show marked changes in fatty acid profile. In phosphatidyl choline there was a significant diminution in arachidonic acid, 20 : 4(n-6) and palmitic acid, 16 : 0, and a corresponding increase in linoleic acid, 18 : 2(n-6), and stearic acid, 18 : 0. In phosphatidyl ethanolamine the level of 20 : 4(n-6) was significantly reduced. The diabetic heart had normal levels of individual phospholipids, whereas the triglycerides were increased by 90% and contained significantly higher levels of 18 : 2(n-6). The results confirm that diabetes is associated with a diminution in fatty acid desaturation, affecting the fatty acid composition of phosphatidyl choline in particular. These changes may be relevant to development of atherosclerosis and relative resistance to catecholamine-induced cardiac necrosis in diabetes.
J Mol Cell Cardiol 1987 Nov
PMID:Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat. 343 62

Of 100 arteriographically examined, hospitalized, male patients, those without myocardial infarctions were divided into the following categories: zero-, one-, two-, and three-vessel disease; patients diagnosed with myocardial infarction were classified separately. The fasting plasma samples from these patients were examined for concentrations of triglycerides and total cholesterol, lipoprotein profile, lecithin: cholesterol acyltransferase (LCAT) activity, and lysolecithin (LPC) concentration. Those parameters in this group which are commonly determined were consistent with the clinical classification of these patients. Of those remaining parameters, the LCAT activity was increased as the severity of coronary atherosclerosis increased and the changes in the activity of this enzyme were appropriately reflected by increases in LPC concentration and decreases in the proportion of the plasma cholesterol unesterified. The results of this study suggest that increased, rather than decreased, plasma LCAT activity and increased LPC concentrations are characteristic of coronary atherogenesis. The plasma concentrations of LPC observed in these atherosclerotic patients are more than sufficient to qualify this substance for its previously proposed roles of mediator of transmembrane diffusion of LDL and as an inhibitor of platelet aggregation.
Exp Mol Pathol 1986 Dec
PMID:Lecithin: cholesterol acyltransferase and lysolecithin in coronary atherosclerosis. 346 3

The lipid constituents in native low-density lipoproteins (LDL), ultra-water-soluble LDL (UWS-LDL), and aortic intimal tissues were compared. These lipoproteins were obtained from healthy persons and patients with atherosclerotic diseases. Also, aortic intimas were separated from arterial walls obtained within 5 hr after the donor's death. (1) From the native LDL, cholesterol esters (CE), triglycerides (TG), small amounts of free fatty cid (FFA), free cholesterol (CF), and phospholipids (PL) were demonstrable by iodine vapor on TLC, but from UWS-LDL the above lipids plus a new lipid (spot X) were observed between TG and FFA on TLC. And also, an unknown spot with the same Rf value as spot X was recognized on TLC of lipid extract from the atherosclerotic lesion, but not from the normal intima. (2) The production of spot X in UWS-LDL is probably related to the oxidation of lipids in native LDL. Also, the spot X in UWS-LDL and the spot X in the atherosclerotic lesions are probably related to the oxidation of CE in these lipids. (3) The existence of UWS-LDL is important to the initiation and probably the progression of atherosclerosis.
Exp Mol Pathol 1987 Oct
PMID:Comparison among lipid constituents in native LDL, ultra-water-soluble LDL, and vessel wall, and their significance in arteriosclerosis. 365 44

The hypothesis was examined that arterial microsomal membrane fluidity is decreased in atherosclerosis. To investigate this hypothesis, the fluorescence anisotropy (r) of 1,6-diphenylhexa-1,3,5-triene was measured in aortic microsomes isolated from normal and atherosclerotic rabbits. A decrease in membrane fluidity, as indicated by a significant increase in r, was observed in microsomes from atherosclerotic rabbits. Notably, the increase in r occurred prior to macroscopic lesion development. The data support the hypothesis that membrane fluidity is decreased in atherosclerosis and indicate that this decrease occurs early in the atherogenic process. The hypothesis that decreased microsomal membrane fluidity contributes to the increased activity of acyl-CoA:cholesterol acyltransferase (ACAT) in atherosclerosis was also investigated. The hypothesis was rejected on the basis that enrichment of microsomes from normal rabbits with exogenous cholesterol to achieve r values equal to that of microsomes from atherosclerotic rabbits did not result in comparable ACAT activity.
Exp Mol Pathol 1986 Dec
PMID:Decreased microsomal membrane fluidity in the development of cholesterol-induced atherosclerosis in the rabbit. 379 13

Using rats made hypertensive by aortic ligation or by the one kidney--one clip method, we searched the aorta for morphologic clues that could explain why hypertension aggravates atherosclerosis. Both atherosclerosis and hypertension are characterized by an increased migration of mononuclear cells into the aortic intima; we therefore quantitated this phenomenon and studied its time course. In the thoracic aorta of hypertensive rats intimal cells (emigrated mononuclear cells) increased up to 15 times 2 weeks after surgery and remained stationary thereafter. In both control and experimental rats, leukocyte emigration was heavier in the thoracic aorta than in the abdominal region. A two- to threefold increase in medial smooth muscle herniae into the intima (myointimal herniae) was also found at 8 weeks, indicating a smooth muscle cell dysfunction. Electron microscopic study of the intima showed that its thickening was due to blood-borne material and also to extracellular matrix synthesized by the endothelium. Heightened secretion reflects cell activation, a condition that (in the endothelium) leads also to leukocyte adhesion. These data suggest that, in renovascular hypertension, the aortic endothelium is in an activated state, possibly through a hormonal stimulus.
Exp Mol Pathol 1986 Dec
PMID:Cellular changes during hypertension: a quantitative study of the rat aorta. 379 15

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.
Exp Mol Pathol 1985 Aug
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.
Exp Mol Pathol 1985 Aug
PMID:Arterial prostaglandins and lysosomal function during atherogenesis. II. Isolated cells of diet-induced atherosclerotic aortas of rabbit. 392 57

We report here the effect of a moderately atherogenic diet on the progression of atherosclerosis among cynomolgus macaques that were either vasectomized or sham vasectomized. Both groups were compared to sham vasectomized monkeys fed a control Monkey Chow diet. As expected, slight hyperlipoproteinemia induced by the moderately atherogenic diet increased endothelial cell replication rates and resulted in the development of intimal lesions among sham vasectomized monkeys. Unexpectedly, vasectomy resulted in reduced leukocyte adherence to arterial surfaces, reduced endothelial cell replication rates in response to the moderately atherogenic diet, and at most arterial sites, smaller intimal lesions were produced. These data suggest that with slight hyperlipoproteinemia vasectomy may result in a small protective effect against atherosclerosis, while other studies have shown that marked hyperlipoproteinemia in cynomolgus macaques along with vasectomy results in exacerbation of atherogenesis.
Exp Mol Pathol 1986 Feb
PMID:Diet and vasectomy: effects on atherogenesis in cynomolgus macaques. 394 76

Glycosaminoglycans (GAG) are believed to be important in the pathogenesis of atherosclerosis. We have previously demonstrated that areas of injured aorta that have been re-endothelialized accumulate increased amounts of lipid and GAG when compared to areas remaining de-endothelialized. We have now examined the net incorporation of labeled precursors into the individual GAG present in both re-endothelialized and de-endothelialized areas of rabbit aorta. Aortic tissue was examined at 2-3 and 10-14 weeks after a denuding injury by incubating tissue minces with [3H]glucosamine and sodium [35S]sulfate for 24 hr. Following incubation, the aortic GAG were isolated and assayed for uronic acid concentration and radioactivity. Results indicate that the total GAG concentration was significantly greater (P less than 0.001) in the re-endothelialized (9.46 +/- 0.29 micrograms/mg lipid-free dry residues (LFDR), mean +/- SE) as compared to de-endothelialized (7.89 +/- 0.43 micrograms/mg LFDR) areas. The concentration in uninjured aorta was 9.01 +/- 0.69. The difference between the injured tissues was attributable to increased concentrations of sulfated GAG. Hyaluronic acid and chondroitin sulfate were the most metabolically active of the GAG in either uninjured or injured aorta, together accounting for over 75% of the 3H label. The 3H specific radioactivities of the four GAG in the short-term, re-endothelialized subgroup were all increased nearly twice that found in uninjured and de-endothelialized tissues. With the exception of heparan sulfate, no significant differences were noted in the 3H specific radioactivities between the re-endothelialized and de-endothelialized areas in the long-term subgroup. These results indicate that, relative to adjacent areas of de-endothelialization, GAG preferentially accumulate in re-endothelialized areas even as early as 2-3 weeks following a denuding injury. Overall, metabolic data suggest that increased synthesis is responsible for this effect, although the net contribution of degradative processes cannot be overlooked since GAG turnover was not specifically examined. Thus, it is possible that regenerated endothelium may modify the GAG metabolism of the arterial wall following arterial injury.
Exp Mol Pathol 1985 Jun
PMID:Altered glycosaminoglycan metabolism in injured arterial wall. 399 53

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.
Exp Mol Pathol 1985 Dec
PMID:A possible mechanism in arterial wall for mediation of sex difference in atherosclerosis. 406 8


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