UMLS:C0004153 - FACTA Search

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

Atherosclerosis and its clinical manifestations are still one of the most important civilization problems. New questions arise: is it really an inevitable process? Are there any rational methods to prevent the development of atherosclerotic changes or to facilitate its regression? The aim of the work was to evaluate the influence of bioflavonoids extracted from milk thistle (Sylibum marianum L), troxerutin (O-(beta-hydroxy-ethyl)-ruozid and lecithin, administered together and as a single therapy, on the experimental atherosclerosis development in rabbits. Sixty male mixed-breed rabbits were randomly assigned to 6 equal groups: I--control, II--fed on fat-rich diet (FR/DB), III--fed on FR-diet and sylimaryn concentrate (S), IV--animals fed on FR-diet and troxerutin (T), V--rabbits fed on FR-diet and soya bean lecithin (L), VI--animals fed on FR-diet and sylimaryn-phospholipid complex (SF). The whole experiment lasted 12 weeks. Following tests have been performed: electrocardiographic, biochemical, pathomorphological (including macroscopic and microscopic evaluations of aorta). Biochemical analysis included: cholesterol concentration (total, low density lipoprotein fraction cholesterol and high density fraction cholesterol), triglycerides, b-lipoproteins, phospholipids, fibrinogen, trace elements (calcium, magnesium, zinc and copper) and dimalonic aldehyde concentration. Concentrations of ascorbyl free radical, total cholesterol, triglycerides, P-450 cytochrome and phospholipids in liver have been estimated. Evident normalization of lipid metabolism and inhibition of atherosclerotic changes have been observed in the group of animals fed on SF complex. Concentrations of total cholesterol, LDL-cholesterol fraction, phospholipids and triglycerides decreased in serum. Decrease of serum dimalonic aldehyde was followed by increase of ascorbyl free radicals concentration in liver. Significant increase of serum zinc has been also noted, which exceeded values observed in control group. Concentration of P-450 cytochrome increased in liver microsomes. Sylimaryn and lecithin showed less anti-atherosclerotic activity, and troxerutin displayed the least anti-atherosclerotic activity (Tab. 1-2, Fig. 1-2). On the basis of the achieved results the following conclusions were drawn: 1) Sylimaryn and lecithin have anti-atherosclerotic activity in rabbits. 2) Sylimaryn-phospholipid complex shows the strongest anti-atherosclerotic activity. 3) The achieved results allow us to undertake clinical trials using SF-complex in prevention and treatment of atherosclerosis.
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PMID:[The effect of bioflavonoids and lecithin on the course of experimental atherosclerosis in rabbits]. 947 22

We investigated the effect of zinc sulfate on the proliferation of cultured bovine aortic smooth muscle cells stimulated with or without growth factors. Zinc had no effect on the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells stimulated with or without platelet-derived growth factor or transforming growth factor beta 1. However, it was shown that stimulation of the [3H]thymidine incorporation by either basic or acidic fibroblast growth factor was significantly potentiated by zinc. Other cations including copper, manganese and nickel did not exhibit such an activity. The present data suggest that zinc is a particular heavy metal which potentiates vascular smooth muscle cell proliferation stimulated by basic and acidic fibroblast growth factors as well as thrombospondin. Zinc may be involved in the intimal hyperplasia of atherosclerosis.
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PMID:Zinc potentiates the stimulation by basic and acidic fibroblast growth factors on the proliferation of cultured vascular smooth muscle cells. 950 72

1. The matrix metalloproteinases are a family of at least 16 zinc-dependent endopeptidases possessing catalytic activity against extracellular matrix components. Some members of this family have been implicated in vascular matrix remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally occurring variant has been identified in the promoter of the stromelysin gene with one allele having a run of five adenosines (5A) and the other having six adenosines (6A). Functional analyses have shown that the 6A allele has a lower promoter activity than the 5A allele, which is probably attributable to preferential binding of a putative transcriptional repressor protein. 3. In patients with coronary artery disease, the 6A allele has been found to be associated with progression of atherosclerosis assessed by sequential quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be over-expressed in certain locations in atherosclerotic plaques, which might contribute to local destruction of connective tissue and thus plaque rupture. In the majority of lesional areas, however, matrix synthesis is likely to outstrip matrix degradation, because matrix accumulation is a major feature of most atheromas. This imbalance favouring matrix deposition is likely to be exacerbated in individuals with the 6A6A genotype in whom stromelysin expression is lower due to the weaker stromelysin promoter.
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PMID:Matrix metalloproteinases: implication in vascular matrix remodelling during atherogenesis. 953 17

Although the body status of zinc and copper in cardiovascular disease (CVD) has been shown to be important little is known about the effect of these trace element alterations on lipolytic enzyme activities in atherosclerosis human subjects. The aim of the present study was to evaluate the multiple relationships between lipase (GEH = glycerol ester hydrolase, EC 3.1.1.3) activity, zinc, copper and lipid concentrations in serum and the arterial wall of men with atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). The mean concentrations of zinc and copper in serum were found to be higher in AO in comparison to AA. Low but significant correlation coefficients for zinc and lipase catalytic activity (r > or = 0.64) and lipase metabolic activity GEH/TAG (r > or = 0.67) were calculated in serum in AA. Multiple correlation coefficients (R) for three variables GEH-Zn-Cu were found to be significant for both AO and AA (R > or = 0.45 and 0.68, respectively) in serum but not in the arterial wall. Multiple relations for GEH/TAG-HDL-C (LDLC)-Zn(Cu) were found to be significant (R > or = 0.63) in serum in AA. The results indicate the influence of zinc and copper on the activity of lipase and lipid concentrations and suggest that the multiple relations may provide a better understanding of the role these elements play in atherosclerosis than relations between 2 substances.
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PMID:Serum glycerol ester hydrolase activity is related to zinc and copper concentrations in atherosclerosis obliterans and aneurysm. 963 11

The roles of superoxide (O2.-), peroxynitrite, and carbon dioxide in the oxidative chemistry of nitric oxide (.NO) are reviewed. The formation of peroxynitrite from .NO and O2.- is controlled by superoxide dismutase (SOD), which can lower the concentration of superoxide ions. The concentration of CO2 in vivo is high (ca. 1 mM), and the rate constant for reaction of CO2 with -OONO is large (pH-independent k = 5.8 x 10(4) M(-l)s(-1)). Consequently, the rate of reaction of peroxynitrite with CO2 is so fast that most commonly used scavengers would need to be present at very high, near toxic levels in order to compete with peroxynitrite for CO2. Therefore, in the presence of physiological levels of bicarbonate, only a limited number of biotargets react directly with peroxynitrite. These include heme-containing proteins such as hemoglobin, peroxidases such as myeloperoxidase, seleno-proteins such as glutathione peroxidase, proteins containing zinc-thiolate centers such as the DNA-binding transcription factors, and the synthetic antioxidant ebselen. The mechanism of the reaction of CO2 with OONO produces metastable nitrating, nitrosating, and oxidizing species as intermediates. An analysis of the lifetimes of the possible intermediates and of the catalysis of peroxynitrite decompositions suggests that the reactive intermediates responsible for reactions with a variety of substrates may be the free radicals .NO2 and CO3.-. Biologically important reactions of these free radicals are, for example, the nitration of tyrosine residues. These nitrations can be pathological, but they also may play a signal transduction role, because nitration of tyrosine can modulate phosphorylation and thus control enzymatic activity. In principle, it might be possible to block the biological effects of peroxynitrite by scavenging the free radicals .NO2 and CO3.-. Because it is difficult to directly scavenge peroxynitrite because of its fast reaction with CO2, scavenging of intermediates from the peroxynitrite/CO2 reaction would provide an additional way of preventing peroxynitrite-mediated cellular effects. The biological effects of peroxynitrite also can be prevented by limiting the formation of peroxynitrite from .NO by lowering the concentration of O2.- using SOD or SOD mimics. Increased formation of peroxynitrite has been linked to Alzheimer's disease, rheumatoid arthritis, atherosclerosis, lung injury, amyotrophic lateral sclerosis, and other diseases.
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PMID:Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. 974 78

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamin A and E and beta-carotene. Trace elements such as selenium, zinc and copper are involved in the activity of antioxidant enzymes: glutathione peroxidase and superoxide dismutase. The aim of this work was to determine the antioxidant and trace elements status of patients with very severe hypercholesterolemia and who were treated by dextran sulphate low density lipoprotein apheresis, in comparison with two control populations: one constituted by normocholesterolemic subjects and the other by hypercholesterolemic patients before treatment. Our results showed that, as compared with normocholesterolemic subjects, patients treated by LDL-apheresis were not deficient in vitamin E, beta-carotene and copper but had low plasma levels of selenium, zinc and vitamin A. The low selenium and vitamin A levels were due to the treatment by LDL-apheresis by itself, while the hypercholesterolemia of these patients might have provoked the low plasma levels of zinc. This study pointed out the interest of a supplement of selenium, zinc and vitamin A in patients treated by LDL-apheresis.
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PMID:[The plasma antioxidant status and trace elements in patients with familial hypercholesterolemia treated with LDL-apheresis]. 977 31

Differentially expressed genes generated by cholesterol-loading in the culture medium of aortic smooth muscle cells (SMC) were screened using the DDRT-PCR technique in order to identify the genes that are possibly involved in the pathogenesis of atherosclerosis in the artery. Twenty-eight genes were initially isolated and three differentially expressed cDNAs were finally selected by Northern blot analysis. All three cDNAs were up-regulated (designated CRGSM-1 through -3) by the cholesterol-loading. Upon nucleotide sequencing and homology search in the databases, the first cDNA (CRGSM-1) had a high homology (97%) with the corresponding segment of the acyl-CoA synthetase II gene from rat brain, which participates in fatty acid synthesis. The second one (CRGSM-2) had a high homology (91%) with a part of Mus musculus (mouse) LIM protein 1, and with human skeletal muscle LIM-protein 1 genes (80%) and the third gene (CRGSM-3) had no significant homology match in the database. A full size cDNA isolated from the cDNA library of rat aortic smooth muscle cell using the CRGSM-2 as a probe was identified to have a high homology with muscle LIM protein (MLP). The isolated cDNA contained a segment of DNA that encodes for a zinc-finger motif and two LIM domains. Proteins bearing the LIM domain, defined as a unique double zinc-finger structure associated with a subclass of proteins involved in the determination of cell identity, cell differentiation and control of cell growth, have previously been suggested to play an important role in the pathogenesis of atherosclerosis by others.
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PMID:Differentially expressed genes in cultured aortic smooth muscle cells by cholesterol-loading. 989 16

Experimental evidence confirms that the matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions that involve connective tissue destruction including osteoarthritis and rheumatoid arthritis, tumor metastasis and angiogenesis, corneal ulceration, multiple sclerosis, periodontal disease, and atherosclerosis. Modulation of MMP regulation is possible at several biochemical sites, but direct inhibition of enzyme action provides a particularly attractive target for therapeutic intervention. Hypotheses concerning inhibition of specific MMP(s) with respect to disease target and/or side-effect profile have emerged. Examples are presented of recent advances in medicinal chemistry approaches to the design of matrix metalloproteinase inhibitors (MMPIs), approaches that address structural requirements and that influence potency, selectivity, and bioavailability. Two important approaches to the design, synthesis, and biological evaluation of MMPIs are highlighted: (1) the invention of alternatives to hydroxamic acid zinc chelators and (2) the construction of nonpeptide scaffolds. One current example in each of these two approaches from our own work is described.
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PMID:Design and synthetic considerations of matrix metalloproteinase inhibitors. 1041 20

Changes were studied in the blood plasma content of trace elements (iron, zinc, manganese, copper and zinc) before and after a 20-day course of treatment in patients with IHD, stable angina, who were given, apart from antianginal therapy, eunicap M having in its composition trace elements (iron, manganese, cuprum, and other trace elements). It has been ascertained that IHD is accompanied by changes in the blood plasma content of trace elements. Combination of eunicap M with antianginal therapy promotes the tendency toward normalization of iron and cuprum metabolism; there was no significant change in the content of zinc and manganese, which fact may be related to a deficient content of manganese in the given drug preparation or a greater demand for them in patients with atherosclerosis.
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PMID:[The correction of the trace element composition of the blood plasma in patients with ischemic heart disease by using Eunicap M]. 1042 18

Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
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PMID:Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer. 1049 17

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