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)

Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.
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PMID:Antiatherosclerotic actions of isradipine. 137 31

To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in stability of PGI2. Free Apo A-I cannot stabilize PGI2. HDL-associated Apo A-I, whose amount is affected by Apo A-II, stabilized PGI2 and correlated well with stability of PGI2 in patients with CAD and control patients. Decreased PGI2 half-life may play an important role in the pathogenesis of atherosclerosis and thrombus formation in the coronary arteries, especially thrombus formation during an acute coronary event.
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PMID:Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris. 211 45

Lipids have important biochemical functions, but their excess in plasma is a risk factor for atherosclerotic disease. After puberty, the plasma total and low-density lipoprotein (LDL) cholesterol concentrations increase with age as a consequence of an increase in production and a decrease in catabolism mediated by LDL receptors. On the other hand, the plasma high-density lipoprotein (HDL) cholesterol concentrations remain constant. The correlation between serum cholesterol and coronary risk becomes weak with age but also exists in the elderly, while low levels of HDL cholesterol remain to be a risk. The rise in serum triglycerides with age results mainly from the increase in body weight and the decrease in physical activity. Dietary polyunsaturated fatty acids (PUFAs) such as linoleic acid protect against progression of atherosclerosis in part by their hypocholesterolemic effect. The proportion of linoleic acid in serum phospholipids decreases with age. This change also is a separate risk factor for cardiac and cerebral infarction. Among many prostanoids, prostaglandin I2 has antiaggregatory and vasodilatory effects and thromboxane A2 has the opposite effects. Lipid peroxides which are produced inevitably from PUFAs may damage biomembranes and might accelerate cellular aging. The questions of whether dietary manipulation can reduce the age-related changes in lipid metabolism and can improve cellular functions are of major importance.
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PMID:[Lipid metabolism and aging]. 219 2

In contrast to the proven association between active smoking and vascular injury, as well as hemostatic imbalance, such a relation is not jet proven for passive smoking. Vascular damage induced by smoking, however, can be seen in the materno-fetal circulation of smoking mothers, being much more pronounced in the umbilical system than in fetal vessels. These lesions show fast recovery after birth. In non-smokers acute exposure to passive smoke induces a short-lasting activation of platelet function and the prostaglandin system, followed by a quick recovery. Chronic exposure of non-smokers to passive smoke, however, results in changes of these parameters comparable to those seen in smokers, characterized by an activation of platelet function and a decrease in platelet sensitivity to the antiaggregatory prostaglandin I2. These results suggest that in non-smokers with atherogenic risk factors passive smoking may contribute to the incidence of atherosclerosis, as well as acute complications (thrombosis).
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PMID:[Do passive smokers have an increased risk of thrombosis?]. 258 91

The role of prostaglandin I2 (PGI2) in the control of DNA synthesis during the cell cycle was investigated in cultured rabbit aortic smooth muscle cells (SMC). SMC at confluency in the G0 state reached the S phase about 16 h after stimulation with serum, as judged by measurement of [3H]thymidine incorporation into DNA (DNA synthesis). Cyclooxygenase inhibitors such as indomethacin and aspirin enhanced DNA synthesis, suggesting that endogenously synthesized prostaglandins inhibit DNA synthesis. Added PGE1 or PGE2 had little effect on DNA synthesis. PGI2 inhibited DNA synthesis only when added from 10 to 16 h after stimulation of SMC in the G0 state with serum. Addition of CS-570, a stable PGI2 analogue, inhibited DNA synthesis at any time after serum stimulation. The endogenous syntheses of PGI2 and DNA were negatively correlated. These results suggest that PGI2 inhibits DNA synthesis by acting on the progression stage of the G1 state.
Atherosclerosis 1988 Jun
PMID:Cell cycle-dependent inhibition of DNA synthesis by prostaglandin I2 in cultured rabbit aortic smooth muscle cells. 304 80

The negative control system for proliferation by prostaglandin I2 (PGI2) was studied in the smooth muscle cells (SMC) cultured from the thickened intima (intimal SMC) of rabbit aortas. Indomethacin was found to enhance DNA synthesis of medial SMC but not that of intimal SMC. Exogenously added PGI2 or its stable analogue, CS-570, was observed to inhibit DNA synthesis of medial SMC enhanced by indomethacin but not that of intimal SMC. These results indicate that medial SMC are negatively controlled by endogenous PGI2 and that intimal SMC have no such negative control system for cell proliferation. This lack of negative control may be one of the mechanisms underlying the rapid growth behavior of intimal SMC as compared to medial SMC.
Atherosclerosis 1988 Sep
PMID:Lack of inhibition of DNA synthesis by prostaglandin I2 in cultured intimal smooth muscle cells from rabbits. 305 79

Treatment of Japanese monkeys for 8 months with a high fat, high cholesterol diet produced atherosclerotic lesions in the aorta and mesenteric arteries, such as fatty dots, streaks and plaques, intimal thickening with accumulation of spindle-shaped cells and macrophages and endothelial cell flattening. Contractile responses of mesenteric arteries from control and atherosclerotic monkeys to electrical stimulation of adrenergic nerves, norepinephrine and angiotensin II did not differ, whereas contractions caused by serotonin in the atherosclerotic monkey arteries were significantly greater. Ketanserin and cinanserin suppressed the serotonin-induced contraction. Relaxations caused by adenosine and K+ (5 mM) were moderately attenuated in atherosclerotic monkey mesenteric arteries, and those by acetylcholine were reduced only slightly or not affected in the arteries or aortas. Relaxations of control and atherosclerotic arteries in response to nitroglycerin, isoproterenol and prostaglandin I2 did not differ. The relaxant response to K+ was reversed to a contraction by ouabain. Acetylcholine-induced relaxations were dependent on the endothelium and suppressed by atropine. Diet-induced atherosclerosis appears to potentiate contractions mediated via serotonergic 5-HT2 receptors and to attenuate relaxations possibly caused by activation of the electrogenic Na+ pump in the smooth muscle cell membrane. Endothelium-dependent relaxations via muscarinic receptors would not evidently be affected in mesenteric arteries and aortas from atherosclerotic Japanese monkeys.
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PMID:Functional and histological changes in mesenteric arteries and aortas from monkeys fed a high cholesterol diet. 324 99

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

In order to investigate the effects of dietary protein level on the development of atherosclerosis and arterial thrombosis, studies were made on platelet function, plasma lipids and aortic prostaglandin I2 biosynthesis in rats. Under the same calorie intake, the group consuming a low level of protein (10% casein) increased plasma triglycerides and platelet aggregability in comparison with control (20% casein) and high protein groups (60% casein). Moreover, the low protein group produced more thromboxane A2 and less prostaglandin I2 compared with the high protein one. These data suggest that high protein diets may have beneficial effects on arterial thrombosis.
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PMID:Effect of dietary protein level on platelet aggregation in rat. 389 45

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


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