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

Mononuclear phagocytes adhere to and penetrate the vessel wall endothelium and contact the subendothelial space prior to the development of the atherosclerotic plaque. In an attempt to model the early events of plaque development we used an elastin-rich, multicomponent, cell-derived matrix from neonatal rat aortic smooth muscle cells as a substratum for monocytes. Using this model, we show that human monocyte morphology and metabolism are markedly altered by the matrix substratum. When a mixed mononuclear cell population is seeded on matrix or plastic, only monocytes adhere to the matrix surface. In contrast, lymphocytes as well as monocytes adhere to the plastic surface. The matrix-adherent monocytes develop large intracellular granules and form extensive clusters of individual cells. Metabolically, these cells develop sodium fluoride resistant non-specific esterase activity and their media contain more growth factor activity and PGE2. Although total protein synthesis is equivalent in both cultures, the matrix contact induces an increase in specific proteins in the media. We also show that a purified alpha-elastin substratum induces some, but not all, of the monocyte changes seen when using the matrix substratum. Using the alpha-elastin substratum, there is selective adhesion of monocytes and increased growth factor activity, however, the cells are morphologically different from the matrix-adherent cells. Thus, the use of the smooth muscle cell-derived matrix, in conjunction with purified matrix components, serves as a model that can provide insight into the mechanisms of monocyte adhesion and stimulation by the matrix environment that exists in vivo. Such mechanisms may be particularly important in atherogenesis.
Atherosclerosis 1990 Dec
PMID:Monocyte activation by smooth muscle cell-derived matrices. 210 75

The correlations between the degree of atherosclerosis, plasma prostaglandins (PGs) and plasma lipids were examined in maintenance hemodialyzed patients with and without diabetes mellitus. The degree of atherosclerosis was evaluated by pulse wave velocity (PWV) of the aorta. Plasma PGs were radioimmunoassayed. PWV was significantly higher in hemodialyzed patients compared to sex- and age-matched healthy controls. PWV correlated with the plasma thromboxane A2 (TXB2) level and TXB2/6-keto-PGF1 alpha ratio in hemodialyzed patients, without a significant difference between the diabetic and nondiabetic groups. The plasma lipid profile was type IV of the WHO classification in both the diabetic and nondiabetic groups, and PWV did not correlate with these lipid abnormalities. Though not significantly, the decreases in plasma PGE2 and 6-keto-PGF1 alpha and the increase in TXB2 correlated with the degree of type IV hyperlipidemia. The results suggest that plasma PG abnormalities might correlate with the degree of atherosclerosis in hemodialyzed patients.
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PMID:Correlation between blood prostaglandins, plasma lipids and atherosclerosis in dialyzed patients. 224 91

Although atherosclerosis is a common disease afflicting the kidney, few studies have examined the biochemical disturbances associated with this process directly in the renal microvasculature. Using a technique developed in this laboratory to isolate renal preglomerular microvessels, we have examined whether these vascular segments have a reduced capacity to synthesize vasodilator prostanoids (i.e., PGI2 and PGE2), an observation which has been made in atherosclerotic blood vessels from other vascular beds. The synthesis of these two prostanoids was assessed by radioimmunoassay in a group of white New Zealand rabbits fed a 2% cholesterol diet for 30 days and the results compared to that obtained in a similar group of rabbits fed a normal diet. The results of these studies showed the development of hypercholesterolemia in the cholesterol-fed rabbits which was associated with a 35% decrease in the biosynthesis of PGI2 and a 51% decrease in PGE2 in freshly isolated renal preglomerular microvessels. These findings are similar to those observed in non-renal major blood vessels and suggest that common biochemical mechanisms may operate in the development of atherosclerosis in many organ systems.
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PMID:Decreased renal preglomerular microvascular PGI2 and PGE2 biosynthesis in cholesterol-fed rabbits. 266 76

The effects of prostaglandin (PG) E1, PGE2, the stable prostacyclin analogue Iloprost, and PGF2 alpha on low density lipoprotein (LDL) receptor activity and cholesterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 45 hr in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of 125I-labeled LDL. Addition of PGE1 in increasing concentrations to the incubation medium inhibited cholesterol synthesis and the specific accumulation and degradation of 125I-labeled LDL; at a concentration of 10 microM, the inhibitions were 61%, 70%, and 67%, respectively, after an incubation of 20 hr. The effects of PGE2 and Iloprost were similar. The action of the prostaglandins on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. The prostaglandins yielded sigmoidal log concentration-effect curves. In contrast, PGF2 alpha had no influence on cholesterol synthesis or LDL receptor activity up to a concentration of 10 microM. PGE1, PGE2, and Iloprost, but not PGF2 alpha, led to an increase in the concentration of intracellular cyclic AMP. Dibutyryl cyclic AMP mimicked the effects of the E-prostaglandins and Iloprost on the LDL receptor activity. The results suggest that PGE1, PGE2, and prostacyclin affect LDL receptor activity and cholesterol synthesis and, therefore, may play a role in the regulation of cholesterol homeostasis and in the development of atherosclerosis.
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PMID:Effects of prostaglandins on LDL receptor activity and cholesterol synthesis in freshly isolated human mononuclear leukocytes. 285 53

The metabolism in vitro of exogenous and endogenous arachidonic acid was studied in circulating blood monocytes obtained from control (control group) and cholesterol (0.5%)-fed (cholesterol group) rabbits. The production of superoxide anion (O2-), tissue plasminogen activator (t-PA) and adherence of monocytes were assessed in both groups of animals. The amounts of cyclooxygenase and lipoxygenase products derived from exogenously added [1-14C]AA were not significantly different in monocytes collected from both groups of animals. However, the amounts of PGD2, TXB2 and PGE2 formed from endogenous substrate were decreased significantly in monocytes obtained from the cholesterol group compared to those from the control group. The production of immunoreactive LTB4 was not suppressed significantly in monocytes collected from the cholesterol group. The production of O2- and t-PA was suppressed significantly in monocytes obtained from the cholesterol group and these cells adhered onto glass surfaces more efficiently than control cells. Since the formation of prostanoids from endogenous but not exogenous substrate is reduced, an effect of cholesterol on the liberation of AA from phospholipid pools is implicated.
Atherosclerosis 1986 Aug
PMID:Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O2-) by rabbit blood monocytes. 301 60

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 synthesis of prostaglandins (PGs) was determined in endothelial cells obtained from various vessels from baboon, human and rat both by radioimmunoassay and prelabel of the cells with [3H] arachidonate. Cells were stimulated with bradykinin, ionophore A23187 or 10 microM arachidonate. Although prostacyclin (PGI2) has proven to be the major prostaglandin product of human umbilical vein and calf pulmonary artery endothelial cells, our results show that PGI2 is frequently not the major prostaglandin product of endothelial cells from other vessels. For example baboon endothelial cells lining the large vessels, aorta and cephalic vein produce mainly PGF2a with only small amounts of PGE2 and PGI2. Human endothelial cells from saphenous vein also produce mainly PGF2a. Baboon, human and rat adipose capillary endothelial cells make predominantly PGE2 and PGI2 with rat making significant amounts of PGF2a in addition. Endothelial cells from the rat aorta produced predominantly prostacyclin.
Atherosclerosis 1987 Jun
PMID:Comparison of prostaglandin synthesis by endothelial cells from blood vessels originating in the rat, baboon, calf and human. 311 42

Interactions between vascular endothelium and low density lipoprotein (LDL) have been implicated in the development of atherosclerosis. The effect of normal and oxidized LDL (Ox-LDL) on prostaglandin release by cultured adult human saphenous vein endothelial cells was investigated. Ox-LDL induced a rapid release of prostacyclin (PGI2) to levels which were several-fold higher than those observed with control LDL. PGI2 release was concentration-dependent and was biphasic, with a first peak occurring within 30 minutes (followed by a decrease), and a second peak occurring after several hours of incubation. PGI2 production was inhibited by lipoprotein-depleted serum and by indomethacin, an antagonist of cyclooxygenase activity. These cells produced mainly PGF2 alpha, with some PGE2 and PGI2 when stimulated by the ionophore A23187 at confluency. However, among these prostanoids, mainly PGI2 was produced in response to Ox-LDL. The data indicate that Ox-LDL induces the production of PGI2 by human vascular endothelial cells. Since Ox-LDL is cytotoxic, this phenomenon may be a manifestation of an early response to injury.
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PMID:Oxidized low density lipoprotein stimulates prostacyclin production by adult human vascular endothelial cells. 314 46

Recent research has implicated dietary fish oils in the reduction of eicosanoids formed from arachidonic acid and amelioration of chronic diseases such as coronary heart disease, atherosclerosis and inflammation. Feeding studies were conducted to determine if the efficacy of dietary n-3 polyunsaturated fatty acids (PUFA) from fish oils was influenced by the quantity of n-6 polyunsaturated fatty acids and the total level of fat in the diet. Groups of mice were fed diets composed of 5 and 20% total fat with varying proportions of linoleic acid as a source of n-6 PUFA. Menhaden oil as a source of n-3 PUFA was fed at two levels of n-6 at each level of total fat. Eicosanoid biosynthesis was stimulated and assayed in the mouse peritoneum using zymosan as an inflammatory stimulus. Production of LTE4 and PGE2 was enhanced by increasing n-6 PUFA in the diet at both levels of total fat. High dietary fat significantly suppressed leukotriene (LT) synthesis. Dietary menhaden oil reduced LTE4 and PGE2 synthesis at both levels of dietary n-6 in the low fat study. In animals on 20% dietary fat menhaden oil significantly reduced LT synthesis only at a relatively low dietary n-6 PUFA. On a high n-6 PUFA high fat diets, menhaden oil did not significant affect LTE4 synthesis in response to zymosan stimulation. The results suggest that the effectiveness of fish oils in reducing eicosanoids in response to specific stimulation is influenced by the level of n-6 and the total quantity of fat in the diet.
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PMID:The effect of dietary fish oils on eicosanoid biosynthesis in peritoneal macrophages is influenced by both dietary N-6 polyunsaturated fats and total dietary fat. 323 61

WHHL rabbits develop progressive atherosclerosis. There are no visible signs of the disease at 1 month, however, by 12 months, the formation of aortic plaques is extensive. This study characterized arachidonic acid (AA) metabolism in 1 and 12 month old WHHL and NZW rabbit aortas. Vessels incubated with 14C-AA and A23187 metabolized AA to a number of oxygenated products as identified by high pressure liquid chromatography. The major AA metabolites produced by WHHL and NZW aortas were 6-keto PGF1 alpha, PGE2, 12- and 15-hydroxyeicosatetraenoic acids (HETEs). The structures of the HETEs were confirmed by gas chromatography-mass spectrometry. Indomethacin blocked the synthesis of prostaglandins (PGs) but not HETEs whereas ETYA, NDGA or removal of the endothelium attenuated the production of both PGs and HETEs. Measurement of 6-keto PGF1 alpha, 12- and 15-HETE by specific radioimmunoassays indicated that as the rabbits aged and as atherosclerosis progressed, aortas lost the ability to synthesize 6-keto PGF1 alpha and 15-HETE. Prior to the development of atherosclerosis, 1 month old WHHL aortas produced 70% less 15-HETE than did NZW aortas. Atherosclerotic aortas from 12 month old WHHLs synthesized 60% less 6-keto PGF1 alpha during stimulation with AA or A23187 than did 12 month old NZW aortas. We conclude that the development and expression of atherosclerosis in WHHL rabbits impairs the ability of aortas to metabolize AA to both PGs and HETEs.
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PMID:Characterization of arachidonic acid metabolism in Watanabe heritable hyperlipidemic (WHHL) and New Zealand white (NZW) rabbit aortas. 323 4


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