Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of normocholesterolemic, specific-pathogen-free chickens with Marek's disease herpesvirus (MDV) has been shown histologically to lead to chronic atherosclerosis like that in humans. The development of herpesvirus-induced atherosclerosis in vivo and the presence of specific Marek's antigen within aortic cells suggested that MDV infection may modify lipid metabolism and lead to significant lipid accumulation. Experiments reported herein were designed to determine the types and quantity of lipid present in aortas from MDV-infected and uninfected chickens between 2 and 8 months of age following infection and assess one possible mechanism of lipid accumulation by evaluating the effect of MDV infection on aortic cholesterol and cholesteryl ester (CE) metabolism. Chromatographic-fluorometric analyses indicated that at 4 and 8 months of age after MDV inoculation, MDV-infected animals had a significant (P less than 0.05) two-fold to threefold increase in total aortic lipid accumulation characterized by significant increases in cholesterol, CE, triacylglycerol, and phospholipid as compared with aortas from uninfected animals. At 8 months of age, similar increases in aortic lipid accumulation were observed in MDV-infected animals as compared with those animals vaccinated with turkey herpesvirus and later challenged with MDV. CE synthetic activity was increased significantly by 50% at 4 months of age in the MDV-infected group as compared with the uninfected group, which could explain the initial increase in CE accumulation. By 8 months of age, the authors also observed a twofold increase in CE synthetic activity and a 30% and 80% reduction in lysosomal and cytoplasmic CE hydrolytic activities, respectively, in aortas of MDV-infected chickens as compared to controls. Moreover, infection with MDV blocked the activation of cytoplasmic CE hydrolytic activity by dibutyryl cyclic AMP or exogenous cyclic AMP-dependent protein kinase. Taken together, these results suggest that lipid accretion in aortas of MDV-infected chickens results, in part, from alterations in cholesterol/CE metabolism during early stages of the disease. These findings support the hypothesis that human atherosclerosis may result from specific herpesvirus infection which can alter lipid metabolism and lead to lipid accretion.
 ...
PMID:Virus-induced atherosclerosis. Herpesvirus infection alters aortic cholesterol metabolism and accumulation. 293 87

The effect of epinephrine on 125I-low density lipoprotein (LDL) uptake and cholesterol metabolism was investigated after a 24 hours pretreatment of cultured human fibroblasts. Epinephrine decreased LDL uptake (binding + internalization) and degradation in a dose-dependent manner. Cholesterol synthesis from 14C sodium acetate and cholesterol esterification measured by 14C oleic acid incorporation into cholesteryl esters were also decreased. These results are in agreement with the general view that epinephrine increases cyclic AMP intracellular level, as it was previously demonstrated that dibutyryl cyclic AMP or isoproterenol treatment of cultured fibroblasts had similar effect on these pathways. The decrease in LDL processing induced by epinephrine could be involved in the worsening effect of epinephrine on atherosclerosis.
 ...
PMID:Epinephrine decreases low density lipoprotein processing and lipid synthesis in cultured human fibroblasts. 300 79

Smooth muscle cells isolated from atherosclerotic lesions of human aorta retain in primary culture their intrinsic in vivo characteristics: namely, enhanced proliferative activity and high lipid levels. We have tested the effect of different compounds on [3H]thymidine uptake and on the levels of phospholipids, triglycerides, cholesterol, and cholesteryl esters in cultured aortic cells. Effects, such as the inhibition of cellular proliferation and/or lowering of the intracellular lipid levels which would be regarded as antiatherosclerotic if exerted in vivo, were observed in vitro by the following compounds: dibutyryl cyclic AMP, cholera toxin, forskolin, methylisobutylxanthine, stable prostacyclin analogues, prostaglandins E2 and D2, verapamil, reserpine, alpha-tocopherol, butylated hydroxytoluene, lipostabil, and high density lipoproteins. In this paper, we discuss the possibility of using a primary culture of smooth muscle cells from an atherosclerotic human aorta for testing drugs for possible antiatherosclerotic activity.
Atherosclerosis 1986 May
PMID:Primary culture of human aortic intima cells as a model for testing antiatherosclerotic drugs. Effects of cyclic AMP, prostaglandins, calcium antagonists, antioxidants, and lipid-lowering agents. 301 16

Cyclic AMP and cyclic GMP content was measured in intima and media of unaffected and atherosclerotic areas of human aorta in a short-term organ culture. It was demonstrated that during short-term cultivation the content of both cyclic nucleotides in tissues is constant. The cyclic AMP content in fatty streaks and atherosclerotic plaques is significantly (2 to 7-fold) lower than in unaffected intima. The cyclic GMP level in atherosclerotic lesions is 1.5 to 3-fold higher than in normal. The content of both cyclic nucleotides in the media underlying fatty streaks is the same as in the normal tissue. In the media underlying atherosclerotic plaques, the cyclic AMP level is decreased compared to the normal. The obtained data indicates serious disorders in the system of cyclic nucleotides during atherosclerosis. Possible consequences of this disfunction are discussed.
 ...
PMID:Cyclic AMP and cyclic GMP content in a short-term organ culture of normal and atherosclerotic human aorta. 302 90

The capacity of vascular tissue in generating PGI2 has been accepted to be a key property in hemostatic balancing at a local level. Earlier it has been shown that PDGF is able to enhance SMC-proliferation. As this process is associated with c-AMP changes which again are influenced by PGI2, the question arose, whether PDGF itself exerts an effect on PGI2-synthesis. Using normal and atherosclerotic human arterial tissue, animal arteries and cultured cells with and without addition of various PDGF-concentrations this question was answered by means of bioassay and RIA-determination in a static and a pulsatile perfusion chamber system as well. In general, between 10 and 50 ng PDGF/ml, a significant increase either in PGI2-formation or 6-oxo-PGF1 alpha can be seen. A similar dose dependent stimulation of PGI2-synthesis can be monitored for vascular tissue and cultured cells as well. Static incubation and perfusion chamber experiments reveal comparable findings of PDGF stimulatory capacity on PGI2-formation. In contrast, no such effect can be seen using human umbilical artery. The half-life of PGI2-formation in the perfusion chamber model is comparable in presence and absence of PDGF as well. The stimulatory effect of PDGF on atherosclerotic vascular tissue is significantly less pronounced than onto normal one. Concluding from our findings we speculate that PGI2 prevents PDGF-release from platelets, thus decreasing smooth muscle cell proliferation and improving cellular lipid metabolism; an insufficient response of vascular tissue onto PDGF to generate PGI2 might be a key event in the pathogenesis of early atherosclerosis favouring a negative vicious cycle.
 ...
PMID:Stimulation of prostacyclin formation by the platelet-derived growth factor--an important pathomechanism for atherogenesis? 305 97

The effect of 12 weeks supplementation with fish oil on the number of anginal attacks and consumption of glyceryltrinitrate in 36 patients with stable angina pectoris was evaluated in a clinically controlled trial using a vegetable oil as placebo. Fish oil caused a decrease in frequency of angina, but was not significantly superior to placebo. However, due to the small sample size and a high spontaneous variation in number of anginal attacks, a risk of up to 50% of overlooking a 30% reduction in anginal attacks could be estimated. A significant inhibition of the epinephrine-induced platelet aggregation and a significant increase in intraplatelet cyclic AMP were induced by fish oil.
Atherosclerosis 1987 Mar
PMID:Fish oil in angina pectoris. 310 45

Prostaglandin, a smooth muscle-stimulating depressor acidic lipid discovered int he human seminal plasma in 1935, is now used as a generic term for a family of closely related derivatives of prostanoic acid which are widely distributed in animal tissues. Prostaglandins are biosynthesized from arachidonic acid and dihomo-gamma-linolenic acid, both of which are derived from dietary linoleic acid. This finding provided a link to the observation that linoleic acid is an essential constituent of the diet. It is possible that prostaglandin compounds play a biochemical role fundamental to many, or all, animal cells. They have been implicated in sperm transport, menstruation, parturition, and control of placental blood flow. They may also play a role in the central nervous system, although this role may well be other than that of synaptic transmitter. Release of prostaglandin from various tissues is brought about by nerve stimulation. In adipose tissues, the amounts released may be sufficient to inhibit formation of cyclic AMP by the released noradrenaline, thus providing a local negative feedback mechanism. Prostaglandins also possibly play a role in muscular contractility, essential fatty acid deficiency, inhibition of lipid mobilization, atherosclerosis, and thrombosis.
 ...
PMID:Hypotheses on physiological roles of prostaglandins. 430 63

The effect of prostaglandins (PG) on initiation of DNA synthesis in arterial smooth muscle cells (SMC) stimulated with platelet-derived growth factor (PDGF) was examined. A concentration of 10 ng/ml PGE1 inhibited DNA synthesis, measured as autoradiographically labeled nuclei, by about 70%. Similar results were obtained with PGE2 and PGD2 but at concentrations 10-20 times higher, whereas PGF2 alpha lacked effect. The inhibitory action of the prostaglandins was restricted to the first 6 h of the lag phase. Treatment with PGE1 also raised the intracellular concentration of cyclic AMP, indicating that the inhibition may be mediated via changes in the levels of cyclic nucleotides.
Atherosclerosis 1984 Oct
PMID:Prostaglandin E1 inhibits DNA synthesis in arterial smooth muscle cells stimulated with platelet-derived growth factor. 609 30

Prostacyclin (PGI2) is the product of arachidonic acid metabolism generated by the vessel wall of all mammalian species studied, including man. Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation so far described. Prostacyclin inhibits aggregation through stimulation of platelet adenyl cyclase leading to an increase in platelet cyclic AMP. In the vessel wall, the enzyme that synthesizes prostacyclin is concentrated in the endothelial layer. Prostacyclin can also be a circulating hormone released from the pulmonary circulation. Based on these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. The discovery of prostacyclin has given a new insight into arachidonic acid metabolism and has led to a new hypothesis about mechanisms of haemostasis. Reductions in prostacyclin production in several diseases, including atherosclerosis and diabetes, have been described and implicated in the pathophysiology of these diseases. Additionally, since prostacyclin powerfully inhibits platelet aggregation and promotes their disaggregation, this agent could have an important use in the therapy of conditions in which increased platelet aggregation takes place and in which, perhaps, a prostacyclin deficiency exists. Prostacyclin has been used beneficially in humans during extracorporeal circulation procedures such as cardiopulmonary bypass, charcoal haemoperfusion and haemodialysis. Its possible use in other conditions such as peripheral vascular disease or transplant surgery is at present being investigated.
 ...
PMID:Prostacyclin: its biosynthesis, actions and clinical potential. 611 93

Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis.
Atherosclerosis 1980 Nov
PMID:Hemodynamic effects on aortic enzyme activities in spontaneously hypertensive rats. 625 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>