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)

Following our microassay for cyclic AMP phosphodiesterase (1978, Microvascular Res. 15:229), a new microassay for cyclic GMP phosphodiesterase (c-GMPPDE) activity was devised, combining the quantitative histochemical method of O.H. Lowry and J.V. Passonneau (1971, A Flexible System of Enzymatic Analysis, Academic Press, New York) with the thin-layer chromatography method of W.A. Scott and B. Solomon (1973, Biochem. Biophys. Res. Comm., 53, 1024). Using this method, c-GMPPDE activity can be accurately measured in a 250 microgram dry weight sample of tissue from the aortic wall. The optimal amount of sample and incubation time were studied, and two Km values were obtained. Low Km is 4.00 x 10(-6) and high Km is 1.25 x 10(-5). The activity of this enzyme was measured in the intima and media of the aorta of three rabbits, three cows and three pigs. The cyclic GMPPDE activities in tissue from cows, pigs and rabbits were 26.61 +/- 2.19, 20.40 +/- 1.35, 43.08 +/- 4.11 pmole/mg dry weight/min in the intima; 52.56 +/- 2.73, 16.07 +/- 3.30 and 66.51 +/- 4.60 pmole/mg dry weight/min in the media. With regard to the relationship between levels of cAMP and cGMP, the activities of cGMPPDE were 10-20 times higher than those of cAMPPDE. These assay systems should provide accurate tools for researching biological, physiological and pathological states of arterial tissues, particularly in the case of atherosclerosis.
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PMID:Microassay of cyclic nucleotides in vessel wall. IV. Cyclic GMP phosphodiesterase activity. 23 54

Phthalazinol (EG 626), a thromboxane A2 antagonist and cyclic AMP phosphodiesterase inhibitor, has been shown to prevent the atherosclerosis induced in cholesterol fed rabbits. In an attempt to clarify the antiatherosclerotic mechanism, the effects of this compound on the lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) of rat aorta were examined in vivo. Administration of EG 626 (100-200 mg/kg, per os, daily, 1-2 weeks) affected neither the aortic lysosomal cholesterol esterase nor the acid phosphatase activity, whereas the lipoprotein lipase activity was signficantly decreased by the treatment. These results suggest that with an elevation in HDL-cholesterol, a decrease in lipoprotein lipase activity after ingestion of EG 626 might contribute, at least to some extent, to the prevention of arterial lipid accumulation.
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PMID:Effects of phthalazinol (EG 626) on arterial lipolytic enzyme activities in the rat. 23 31

The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors.
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PMID:Hyperreactive arterial endothelial cells in atherogenesis and cyclic AMP phosphodiesterase inhibitor in prevention and treatment of atherosclerotic disorders. 23 47

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.
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PMID:Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. 128 92

Most studies on garlic during the past 15 years have been primarily in the fields of cardiovascular and cancer research. Cardiovascular studies have been mainly related to atherosclerosis, where effects were examined on serum cholesterol, LDL, HDL, and triglycerides. Although the studies were not consistent in relation to the dosage, standardization of garlic preparations, and period of treatment, most findings suggest that garlic decreases cholesterol and triglycerides levels in patients with increased levels of these lipids. Lowering of serum lipids by garlic ingestion may decrease the atherosclerosis process. The other major beneficial effect of garlic is due to its antithrombotic actions. This field of garlic research has been extensively studied. Garlic extracts and several garlic constituents demonstrate significant antithrombotic actions both in vitro and in vivo systems. Allicin and adenosine are the most potent antiplatelet constituents of garlic because of their in vitro effects. Since both allicin and adenosine are rapidly metabolized in human blood and other tissues, it is doubtful that these compounds contribute to any antithrombotic actions in the body. In addition, ajoene also seems not to be an active antiplatelet principle, because it is not naturally present in garlic, garlic powders, or other commercial garlic preparations. Only a small amount of ajoene can be found in garlic oil-macerates; however, ajoene is being developed as a drug for treatment of thromboembolic disorders. Recent findings on the identification of potent enzyme inhibiting activities of adenosine deaminase and cyclic AMP phosphodiesterase in garlic extracts are interesting, and may have a significant role in the pharmacological actions in the body. Presence of such enzyme inhibitors in garlic may perhaps explain several clinical effects in the body, including the antithrombotic, vasodilatory, and anticancer actions. Epidemiological studies have suggested that garlic plays a significant role in the reduction of deaths caused by malignant diseases. This had led many investigators to examine garlic and garlic constituents for their antitumor and cytotoxic actions both in vitro and in laboratory animals. The data from these investigations suggest that garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. In summary, the epidemiological, clinical, and laboratory data have proved that garlic contains many biologically and pharmacologically important compounds, which are beneficial to human health from cardiovascular, neoplastic, and several other diseases. Numerous studies are in progress all over the world to develop effective and odorless garlic preparations, as well as to isolate the active principles that may be therapeutically useful.
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PMID:Therapeutic actions of garlic constituents. 878 16

To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP phosphodiesterase III, suppresses neointimal formation in balloon-injured carotid artery of the rat, 20 mg of cilostazol was topically applied using pluronic gel at the time of balloon injury. Rats were sacrificed 14 days after balloon injury to measure the extent of neointimal formation. Plasma and tissue concentrations of cilostazol were also measured at 1, 3, 7 and 14 days after topical application. The 5-bromo-2'-deoxyuridine (BrdU, a thymidine analogue) was given intraperitoneally to detect proliferation of smooth muscle cells in the injured media at 3 days after balloon injury. At 1 day after injury, plasma and tissue concentrations were 0.147+/-0.043 microg/ml and 1380 microg/g tissue. Although the plasma concentration of cilostazol was undetectable ( < 0.02 microg/ml), a significant amount of cilostazol (46 microg/g tissue) was still detected in the tissue at the site of application even after 2 weeks. The intimal area of the injured carotid after 2 weeks was significantly smaller in the cilostazol-treated group than in the gel-treated control group (0.06+/-0.01 vs 0.15+/-0.02 mm2, P<0.001). BrdU-positive smooth muscle cells in the injured media after 3 days were also significantly fewer in the cilostazol-treated group than in the gel-treated control group (4.3+/-0.5 vs 9.1+/-0.9% of total cells, P < 0.001). These results suggest that local administration of cilostazol using pluronic gel maintains a high concentration of the drug at the application site, has an anti-proliferative effect on smooth muscle cells, and may have potential for clinical therapeutic use for the prevention of restenosis following arterial intervention.
Atherosclerosis 1999 Jan
PMID:Effects of a single local administration of cilostazol on neointimal formation in balloon-injured rat carotid artery. 992 May 4

The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.
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PMID:New advances in identifying genetic anomalies in stroke-prone probands. 1279 73

The past several years have been marked by significant progress in identifying genetic anomalies in stroke-prone probands. These advances have occurred in both highly penetrant single-gene disorders and in common stroke, which is influenced by risk/susceptibility genes. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be challenging to diagnose because of the wide range of notch 3 mutations that can cause disease, but a new immunohistochemical technique using a skin biopsy sample appears to be highly sensitive and specific. In a landmark Icelandic study, linkage was established between stroke and a locus on chromosome 5q12 designated STRK1. Association studies continue to identify polymorphisms that predispose to stroke and to markers for cerebrovascular atherosclerosis, such as intima-media thickness. Intense interest now surrounds genes involved in inflammation, including genes that encode for the interleukin-1 receptor antagonist and paraoxonase-1. In the foreseeable future, prevention, diagnosis, and treatment will incorporate genetic data to refine and individualize management of cerebrovascular disease.
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PMID:New advances in identifying genetic anomalies in stroke-prone probands. 1532 9

Stroke is the third largest cause of death and a major cause of adult disability and mortality worldwide. Experimental evidence suggests that genetic determinants do contribute a large part to stroke risk. The identification of phosphodiesterase 4D gene as a risk factor for stroke caused a great deal of interest in stroke genetics. Many of the studies of PDE4D gene have focused on the original Icelandic findings but the association between specific SNPs and haplotypes has been inconsistent. The aim of the present study was to investigate the association of three SNPs 32 (rs 456009), 83 (rs 966221) and 87 (rs 2910829), originally described by deCODE group; with stroke in a South Indian population from Andhra Pradesh. Two hundred and fifty ischemic stroke patients and two hundred and fifty controls were included in the study. The stroke patients were sub typed according to TOAST classification. SNP 83 showed significant association with stroke in the population under study while SNPs 87 and 32 were monomorphic. Further SNP 83 was found to be significantly associated with two stroke subtypes, intracranial large artery atherosclerosis (the most frequent subtype in the population) and small artery occlusion. The association with other subtypes was found to be insignificant. Further, SNP 83 was found to be associated significantly with some conventional stroke risk factors like diabetes and smoking.
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PMID:Phosphodiesterase 4D (PDE4D) gene variants and the risk of ischemic stroke in a South Indian population. 1960 1

In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke. Consecutive patients with MRI proven ischemic stroke undergoing MRA were included in this study. The severity of atherosclerotic stenosis on MRA was categorized into moderate 50%-80%, severe 80%-99%, and total occlusion 100% using NASCET criteria. The polymorphism in SNP 32, SNP 83 and SNP 87 of PDE4D gene was analyzed by PCR both in the patients and in 188 controls. Among the 148 patients, MRA was abnormal in 77% patients; ECMRA in 53.8%, ICMRA in 66% and both were abnormal in 42% patients. The frequency of CC genotype of PDE4D83 was significantly higher in the patients with ischemic stroke compared to controls (OR 3.38, 95% CI 1.61-7.11, P= 0.001). The frequency of TT genotype of PDE4D87 was significantly higher ICMRA abnormalities (20%) compared to normal ICMRA (2%). The genotype and allele frequency of PDE4D83 and PDE4D32 were not significantly related to MRA abnormalities. The role of PDE4D87 in atherosclerosis needs confirmation in larger studies.
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PMID:Phosphodiesterase 4 D gene polymorphism in relation to intracranial and extracranial atherosclerosis in ischemic stroke. 2204 24


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