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)

Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis. We determined the effect of pharmacological doses of DHEA upon the adhesion of monocytic U937 cells to human umbilical vein endothelial cells (HUVEC), as well as the expression of adhesion and chemoattractant molecules, the translocation of NF-kappaB, the degradation of IkappaB-alpha and the production of reactive oxygen species (ROS) in HUVEC. Adhesion of U937 cells to DHEA-treated HUVEC was evaluated by co-culture experiments using [(3)H]-thymidine-labeled U937 cells. The expression of adhesion and chemoattractant molecules was evaluated by flow cytometry and RT-PCR, respectively; NF-kappaB translocation was determined by Electrophoretic Mobility Shift Assay (EMSA) and IkappaB-alpha degradation by Western blot. ROS production was determined by the reduction of fluorescent DCFDA. TNF-alpha was used to induce inflammatory responses in HUVEC. One hundred micromolar of DHEA-treatment inhibited the TNF-alpha-induced expression of ICAM-1, E-selectin, ROS production and U937 cells adhesion to HUVEC, and interfered with NF-kappaB translocation and IkappaB-alpha degradation. DHEA at the above mention concentration also inhibited the mRNA expression of MCP-1 and IL-8 in basal conditions but not in TNF-alpha-stimulated conditions. Our results suggest that DHEA inhibits the expression of molecules involved in the inflammatory process, therefore it could be used as an alternative in the treatment of chronic inflammatory diseases such as atherosclerosis.
Atherosclerosis 2007 Jan
PMID:Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in human umbilical vein endothelial cells. 1657 24

Dyslipidemia is one of the possible risk factors for advanced atherosclerosis in patients with chronic renal failure. Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in patients with renal failure. The aim of this study was to determine specific characteristics of plasma and erythrocyte phospholipid content and fatty acid composition in 37 patients with chronic renal failure on hemodialysis (HD). The results were compared with the characteristics of healthy subjects. Briefly, plasma triglyceride (p < 0.001), total cholesterol (p < 0.05), and total phospholipids (p < 0.01) levels were significantly higher and HDL-cholesterol level significantly lower (p < 0.01) in HD patients. Plasma phosphatidylcholine and phosphatidylethanolamine concentration were significantly higher (p < 0.001) in HD patients. The plasma phospholipid fatty acids composition indicated significantly (p < 0.01) higher level of oleic (18:1 n-9) and lower levels of eicopentaenoic (20:5 n-3 EPA) and docosahexaenoic (22:6 n-3 DHA) acids (p < 0.05). However, in HD patients, the relative concentration of plasma phospholipid n-6 polyunsaturated fatty acid (PUFA) was significantly lower (p < 0.05). The fatty acid composition of erythrocyte phospholipid in HD patients was modified with EPA and DHA levels significantly lowered (p < 0.05). Our results demonstrate an abnormal phospholipid metabolism and deficiency of n-3 PUFA in plasma and erythrocyte phospholipids in hemodialyzed patients.
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PMID:Plasma and erythrocyte phospholipid fatty acids composition in Serbian hemodialyzed patients. 1670 92

In their current guidelines cardiac societies recommend the consumption of the two n-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1beta, IL-2, IL-6, TNFalpha, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, in in vitro and animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F(2) isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-kappaB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.
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PMID:n-3 PUFA in CVD: influence of cytokine polymorphism. 1746 99

Peripheral arterial disease (PAD) is an atherosclerotic disease. Evidence suggests that atherosclerosis is an inflammatory condition and long chain n-3 fatty acids, found in oily fish and fish oils, have been shown to reduce inflammation. Genetic and lifestyle factors such as body mass index (BMI) also influence inflammation. In this study we have examined the effect of fish oil in patients with claudication secondary to PAD. Fish oil supplementation, providing 1g EPA and 0.7 g DHA per day for 12 weeks, increased walking distance on a treadmill set at 3.2 km/h with a 7% incline. Walking distance to first pain increased from 76.2+/-8.5 m before fish oil to 140.6+/-25.5 m after fish oil (mean+/-SEM, p=0.004) and total distance walked increased from 160.0+/-21.5 m before fish oil to 242.1+/-34.5 m after fish oil (p=0.002). Fish oil supplementation also improved ankle brachial pressure index (ABPI) from 0.599+/-0.017 before fish oil to 0.776+/-0.030 after fish oil (p<0.001). The increase in walking distance was dependent on both BMI and genotype for single nucleotide polymorphisms in the genes encoding the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin (IL)-1beta and the anti-inflammatory cytokine IL-10 (detected using amplification refractory mutation system polymerase chain reaction). Neither BMI nor any of the genotypes examined affected the ability of fish oil to increase ABPI. The mechanisms by which fish oil affects walking distance and ABPI do not appear to be the same.
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PMID:Fish oil induced increase in walking distance, but not ankle brachial pressure index, in peripheral arterial disease is dependent on both body mass index and inflammatory genotype. 1760 Jun 95

n-3 Polyunsaturated fatty acids are assumed to play an important role in the prevention and treatment of atherosclerosis. Endothelial nitric-oxide synthase (eNOS) is responsible for cardiovascular homeostasis involving in regulation of vascular function, and the subcellular localization is critical for its activation. Here we determined the effect of docosahexaenoic acid (DHA, 22:6 n-3) on distribution of eNOS and its activity. DHA treatment markedly altered lipid environment of caveolae microdomains, which was coincided with selective displacement of caveolin-1 and eNOS from caveolae. Akt was not detected in caveolae fractions and CaM was distributed in both of caveolin-1-enriched membranes and non-caveolar fractions, whose distribution was unaffected by DHA. These data demonstrated for the first time that DHA altered caveolae microenvironment not only by modifying membrane lipid composition, but also by changing distribution of major structural proteins. DHA-induced alterations in caveolae lipid/protein environment may be an important mechanism in the development of pathogenesis of atherosclerosis.
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PMID:Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae. 1766 56

It is well known that serum levels of DHEA and its sulfate form DHEA-S decline along with aging. This phenomenon is called adrenopause in contrast to menopause. Experimental studies show that DHEA has many beneficial effects such as anti-diabetic, anti-atherosclerosis, and anti-osteoporosis effects. Therefore, DHEA replacement has been performed as anti-aging therapy. Several clinical trials of DHEA replacement demonstrated the improvement of sense of well-being, lipid metabolism, and bone metabolism. We recently reported on the result of short-term administration of DHEA in healthy Japanese volunteer men. It is thought that further accumulation of original data is necessary to promote DHEA replacement therapy in Japan.
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PMID:[Hormone replacement Up-to-date. Adrenopause and DHEA replacement therapy]. 1776 21

Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis, most likely mediating an anti-inflammatory action. In order to understand the mechanisms involved in this protection, we evaluated the effects of DHEA on several molecules involved in the inflammatory response. Reactive oxygen species (ROS), expression of adhesion molecules, activation of the NF-kappaB/IkappaB-alpha pathway and of the AP-1 transcription factor were evaluated in human umbilical vein endothelial cells (HUVECs) treated with oxidized low density lipoproteins (oxLDL) and DHEA. We also determined if DHEA affected LDL oxidation in vitro. 100 microM DHEA-treatment inhibited the oxLDL-induced expression of ICAM-1, VCAM-1, PECAM-1, ROS production, and U937 cells adhesion to HUVECs. DHEA also delayed the kinetics of LDL oxidation in vitro. While DHEA did not affect the translocation of NF-kappaB neither the degradation IkappaB-alpha, it led to an increased translocation of AP-1. Our results suggest that DHEA inhibits the expression of molecules involved in the inflammatory process in endothelial cells activated with oxLDL, therefore its potential anti-inflammatory properties should be evaluated for the treatment of chronic inflammatory diseases such as atherosclerosis.
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PMID:Dehydroepiandrosterone delays LDL oxidation in vitro and attenuates several oxLDL-induced inflammatory responses in endothelial cells. 1789 54

Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.
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PMID:Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health. 1790 42

Adrenal function and aging have been the object of intense interest recently, especially as regards dehydroepiandrosterone sulfate (DHEA-S), which is of major importance, since it is distinct from cortisol and aldosterone in declining with age. In a group of healthy old Tunisians, we investigated the association between cortisol and DHEA-S, on the one hand, and age, sex, lifestyle, physical health, including the body mass index (BMI), physical activity, and smoking indicators, on the other hand. We observed that cortisol concentrations did not change with aging, while DHEA-S concentrations decrease with age in both sexes. Cortisol/DHEA-S ratio, however, increases with aging. Our results revealed that DHEA-S levels are affected neither by physical activity nor by weight. It appears also that current smoking could not affect the level of DHEA-S. Relationships were found between DHEA-S concentrations and BMI, then between DHEA-S levels and serum cholesterol, triglycerides and calcium. No modification in the morning serum cortisol was found to be associated with aging. Decrease in DHEA-S levels is, however, clearly associated with this phenomenon. High cortisol/DHEA-S ratio accelerates the occurrence of some adult diseases, such as diabetes mellitus, atherosclerosis, dementia, and osteoporosis. Generally, the adrenal insufficiency marked by a cognitive impairment, immune disorders, sexual dysfunction, and scores for depression and anxiety can be corrected by a replacement of deficient DHEA-S.
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PMID:Hormonal status of cortisol and dehydroepiandrosterone sulfate in an elderly Tunisian population. 1790 95

Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These findings support and complement those already published for RA and other autoimmune diseases. Because of the paucity of data on the hormonal status of patients with JRA, studies on the relationship between hypoandrogenicity and predisposition to develop JRA, and/or disease progression have not been conducted. In addition, despite the rapid expansion of research in the clinical use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity, diabetes mellitus, insulin resistance and hypertension, their potential beneficial effects in JRA/RA have not been fully investigated. In fact, clinical trials of adrenal androgens in RA have only been conducted for the treatment of systemic lupus erythematosus. Further studies using prospective approaches are necessary to provide a unified consensus on the hormonal status of patients with JRA (as well as those with RA). This overview of our knowledge of the putative role(s) of hormones in arthritis will hopefully stimulate researchers in basic science and rheumatologists to synergistically collaborate in the effective translation of such knowledge to new clinical approaches.
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PMID:Could hormones make a difference in the treatment of juvenile rheumatoid arthritis? 1803 14


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