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)

The reactivity of the vascular wall to endothelin-1 (ET-1) is influenced by cholesterol, which is of possible importance for the progression of atherosclerosis. To elucidate signaling steps affected, the cholesterol acceptor methyl-beta-cyclodextrin (mbetacd, 10 mmol/L) was used to manipulate membrane cholesterol and disrupt caveolae in intact rat arteries. In endothelium-denuded caudal artery, contractile responsiveness to 10 nmol/L ET-1 (mediated by the ETA receptor) was reduced by mbetacd and increased by cholesterol. Neither ligand binding nor colocalization of ETA and caveolin-1 was affected by mbetacd. Ca2+ inflow via store-operated channels after depletion of intracellular Ca2+ stores was reduced in mbetacd-treated caudal arteries, as shown by Mn2+ quench rate and intracellular [Ca2+] response. Expression of TRPC1, 3, and 6 was detected by reverse transcriptase-polymerase chain reaction, and colocalization of TRPC1 with caveolin-1 was reduced by mbetacd, as seen by immunofluorescence. Part of the contractile response to ET-1 was inhibited by Ni2+ (0.5 mmol/L) and by a TRPC1 blocking antibody. In the basilar artery, exhibiting less store-operated channel activity than the caudal artery, ET-1-induced contractions were insensitive to the TRPC1 blocking antibody and to mbetacd. Increased store-operated channel activity in basilar arteries after organ culture correlated with increased sensitivity of ET-1 contraction to mbetacd. These results suggest that cholesterol influences vascular reactivity to ET-1 by affecting the caveolar localization of TRPC1.
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PMID:Cholesterol depletion impairs vascular reactivity to endothelin-1 by reducing store-operated Ca2+ entry dependent on TRPC1. 1455 Dec 43

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy.
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PMID:Oral tolerance. 1604 53

Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.
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PMID:Divergent action of calcium channel blockers on ATP-binding cassette protein expression. 1630 3

In large cohort studies, it is common that a subset of the regressors may be missing for some study subjects by design or happenstance. In this article, we apply the multiple data augmentation techniques to semiparametric models for epidemiologic data when a subset of the regressors are missing for some subjects, under the assumption that the data are missing at random in the sense of Rubin (2004) and that the missingness probabilities depend jointly on the observable subset of regressors, on a set of observable extraneous variables and on the outcome. Computational algorithms for the Poor Man's and the Asymptotic Normal data augmentations are investigated. Simulation studies show that the data augmentation approach generates satisfactory estimates and is computationally affordable. Under certain simulation scenarios, the proposed approach can achieve asymptotic efficiency similar to the maximum likelihood approach. We apply the proposed technique to the Multi-Ethic Study of Atherosclerosis (MESA) data and the South Wales Nickel Worker Study data.
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PMID:Multiple augmentation with partial missing regressors. 1654 14

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.
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PMID:Oral tolerance: therapeutic implications for autoimmune diseases. 1716 57

Magnetic nanoparticles with appropriate surface coatings are increasingly being used clinically for various biomedical applications, such as magnetic resonance imaging, hyperthermia, drug delivery, tissue repair, cell and tissue targeting and transfection. This is because of the nontoxicity and biocompatibility demand that mainly iron oxide-based materials are predominantly used, despite some attempts to develop 'more magnetic nanomaterials' based on cobalt, nickel, gadolinium and other compounds. For all these applications, the material used for surface coating of the magnetic particles must not only be nontoxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. Magnetic nanoparticles can bind to drugs and an external magnetic field can be applied to trap them in the target site. By attaching the targeting molecules, such as proteins or antibodies, at particles surfaces, the latter may be directed to any cell, tissue or tumor in the body. In this review, different polymers/molecules that can be used for nanoparticle coating to stabilize the suspensions of magnetic nanoparticles under in vitro and in vivo situations are discussed. Some selected proteins/targeting ligands that could be used for derivatizing magnetic nanoparticles are also explored. We have reviewed the various biomedical applications with some of the most recent uses of magnetic nanoparticles for early detection of cancer, diabetes and atherosclerosis.
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PMID:Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. 1771 88

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.
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PMID:Relationship between serum nickel and homocysteine concentration in hemodialysis patients. 1846 90

On the basis of previous observations that: (1) both the nickel (Ni) concentration in ambient air fine particulate matter (PM(2.5)) and daily mortality rates in New York City (NYC) were much higher than in any other US city; and (2) that peaks in Ni concentration was strongly associated with cardiac function in a mouse model of atherosclerosis, we initiated a study of the spatial and seasonal distributions of Ni in NYC and vicinity to determine the feasibility of productive human population-based studies of the extent to which ambient fine particle Ni may account for cardiovascular health effects. Using available speciation data from previous studies at The New York University, Environmental Protection Agency's Speciation Trends Network; and the Interagency Monitoring of Protected Visual Environments network, we determined that Ni in NYC is on average 2.5 times higher in winter than in summer. This apparent seasonal gradient is absent, or much less pronounced, at NJ and CT speciation sites. Ni concentrations at a site on the east side of Manhattan and at two sites in the western portion of the Bronx were a factor of two higher than at a site on the west side of Manhattan, or at one at Queens College in eastern Queens County, indicating a strong spatial gradient within NYC. We conclude that the winter peaks of fine particle Ni indicate that space heating, which involves the widespread reliance on residual oil combustion in many older residential and commercial buildings in NYC, is a major source of ambient air Ni. Epidemiologic studies based on data generated by a network of speciation sites throughout NYC could effectively test the hypothesis that Ni could account for a significant portion of the excess mortality and morbidity that have been associated with elevated mass concentrations of PM(2.5).
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PMID:Residual oil combustion: a major source of airborne nickel in New York City. 1884 Nov 66

A stent is a medical device that can provide scaffolding to vessels and organ walls to keep the arteries open. Different types of stents have been used in the filed of neurovascular diseases, such as atherosclerosis and aneurysms. Carotid artery stenting (CAS) was approved in 2007 in Japan, and it has been widely used as an alternative to carotid endarterectomy (CEA) for treating severe carotid artery stenosis. According to current approval, the indications of carotid artery stenting are observed in high-surgical-risk patients, patients with more than 50% symptomatic stenosis, and those with more than 80% asymptomatic stenosis. The use of nickel-titanium (nitinol) crush-resistant self-expanding stents (Precise) and emblic-protection devices (Angioguard XP) has been approved. Intracranial atherosclerotic disease have frequently posed a risk for recurrent stroke despite the intensive medical treatment. The design of the Wingspan stent system is different from that of balloon-expandable stents. Target lesions are predilated with an undersized angioplasty balloon, followed by stent deployment. Another important indication is for intracranial aneurysms. Since the discovery Guglielmi dechatable coils (GDC) in the early 1990s, endovascular treatment has been drastically improved all over the world. However, a high recurrence rate is observed when large and wide-necked aneurysms are treated with detachble coils. The application of self-expanding stents such as Neuroform, Enterprize, or LEO, is effective for packing coils into the aneurysm, and flow modification effect can be achieved for the curative reconstruction of the parent arteries. Further reserch will confirm the application of stents for the treatment of cerebrovascular disease.
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PMID:[Stent for neurovascular diseases]. 1980 1

The aim of this study was to investigate if blood levels of trace and/or heavy metals are related to atherosclerosis in a cross-sectional study in elderly. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects, all aged 70), the prevalence of carotid artery plaques was recorded by ultrasound. The numbers of carotid arteries with plaques (0, 1 or 2) were recorded. Also the thickness (IMT) and gray scale (IM-GSM) of the intima-media complex were measured together with plaque echogenicity. Eleven heavy metals and trace elements were analyzed in whole blood, using inductively coupled plasma-sector field mass spectrometry. Nickel levels were related to the number of carotid arteries with plaques in an inverted U-shaped manner after multiple adjustment for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use (p=0.026). IM-GSM and plaque echogenicity were both inversely related to chromium in a linear fashion, and to aluminum in an inverted U-shaped manner (both p<0.0001 for IM-GSM). The relationships between metals and IMT were modest. Circulating levels of some metals, like nickel, aluminum and chromium, were related to atherosclerotic plaques or the echogenicity of the IM-GSM and overt plaques independently of cardiovascular risk factors, including lipids.
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PMID:Circulating levels of metals are related to carotid atherosclerosis in elderly. 2217 28


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