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)

Levels of total cholesterol (TC), triglyceride (Tg), high-density-lipoprotein-cholesterol (HDL-C), apolipoproteins A and B (ApoA and ApoB), were assayed in the serum of 63 patients suffering from coronary atherosclerosis, who survived myocardial infarction (M.I.) compared to healthy subjects. TC was assayed by an enzymatic-colorimetric technique: after precipitation with PEG 6000 the same method was used to determine HDL-C. Tg were assessed using total enzymatic method and ApoA and ApoB by RID. On the basis of TC, Tg, HDL-C, ApoA and ApoB values we have identified 6 main patterns, presenting a very characteristic lipaemic model. No significant difference was found between survivors and controls as regards TC and Tg; on the contrary, there was a statistical difference between the two groups for HDL-C, ApoA and ApoB.
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PMID:[Lipid variations in coronary disease]. 712 68

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.
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PMID:Modulation of antioxidant enzyme expression and function by estrogen. 1281 84

Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for monocytes, is thought to play a major role in atherosclerosis, but whether its atherogenic effects involve the direct modulation of vascular smooth muscle cell (SMC) functions remains unclear. This study examined the effects of MCP-1 on the migration of cultured A7r5 SMCs and the signaling pathways involved. Addition of recombinant MCP-1 stimulated SMC migration in modified Boyden chambers coated with type I collagen in a concentration-dependent manner, with 10(-9) M being maximally effective. Using untreated A7r5 cells, two MCP-1 receptors, CCR2 and CCR4, were detected and MCP-1 secretion was significantly increased by stimulation with platelet-derived growth factor. MCP-1-stimulated A7r5 migration was completely blocked by the NAD(P)H oxidase inhibitor, diphenylene iodonium (DPI), and dose-dependently inhibited by polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), suggesting a role for reactive oxygen species (ROS) in this process. During MCP-1 stimulation, ROS production increased rapidly, then gradually decayed over 60 min, and this effect was markedly decreased by pretreatment with DPI or PEG-SOD. Interestingly, U0126 and PD98059, which inhibit activation of extracellular signal-regulated kinases 1/2 (ERK 1/2), significantly inhibited MCP-1-activated ROS generation. Furthermore, transfection of an active mutant of MEK1 (ERK 1/2 kinase) markedly increased superoxide production in rat aortic smooth muscle cells, as detected by dihydroethydium staining, suggesting that ERK 1/2 activation stimulates ROS generation. ERK 1/2 activation was increased for at least 30 min in cells incubated with MCP-1, and this effect was abolished by U0126 or DPI pretreatment. These results demonstrate that MCP-1 is a chemoattractant for SMCs and that MCP-1-stimulated migration requires both ROS production and ERK 1/2 activation in a positive activation loop, which may contribute to the atherogenic effects of MCP-1.
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PMID:Reactive oxygen species and ERK 1/2 mediate monocyte chemotactic protein-1-stimulated smooth muscle cell migration. 1591 91

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.
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PMID:Is the use of fullerene in photodynamic therapy effective for atherosclerosis? 1804 Jul 38

The increased expression of VCAM-1 on endothelial segments within plaque regions could be used as a target to deliver polymeric drug carriers selectively to sites of atherosclerosis. We probed the hypothesis that polymeric particles conjugated with a ligand for VCAM-1 exhibit selective and avid adhesion to sites of atherosclerosis. Particles made from polystyrene or the biodegradable polymer poly(sebacic acid)-block-polyethylene glycol (PSA-PEG) were conjugated with an antibody to VCAM-1 (alpha-VCAM-1) or IgG (negative control). The particles were injected into the jugular vein of ApoE(-/-) (a murine model of atherosclerosis) or wild type mice and their adhesion to the aorta determined. alpha-VCAM-1 particles exhibited significantly greater adhesion to ApoE(-/-) mouse aorta [32 +/- 5 (mean +/- SEM) particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles] compared to the level of adhesion to wild type mouse aorta (18 +/- 1 particles/mm(2) for polystyrene particles and 6 +/- 1 particles/mm(2) for PSA-PEG particles). Within ApoE(-/-) mice, the alpha-VCAM-1 particles exhibited significantly greater adhesion to the aorta (32 +/- 5 particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles) compared to the adhesion of IgG particles (1 +/- 1 particles/mm(2) for polystyrene particles and 2 +/- 1 particles/mm(2) for PSA-PEG particles). Detailed analysis of the adhesion revealed that alpha-VCAM-1 particles exhibited focal adhesion to plaque regions, in particular the periphery of the plaques, within the ApoE(-/-) mouse aorta. Combined the data demonstrate that polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid and focal adhesion to sites of atherosclerosis providing strong evidence that VCAM-1 ligand bearing polymeric particles could be used for targeting drugs selectively to atherosclerotic tissue.
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PMID:Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis. 1842 14

Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 microm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.
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PMID:Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI. 1879 5

A water-soluble, 19-mer peptide fragment of serum amyloid A called MFFD is being examined as a possible treatment for atherosclerosis. As a means of administering this drug in a sustained fashion through subcutaneous implantation, a biodegradable network formulation was prepared. The formulation consisted of 1000 and 4000Da alpha,omega-diacrylate oligo(d,l-lactide)-b-poly(ethylene glycol)-b-oligo(d,l-lactide) (DLPEGDLDA) copolymerized with 2700 and 5000Da omega,omega,omega-triacrylate star-poly(epsilon-caprolactone-co-d,l-lactide) using UV irradiation. The influence on the network properties and degradation rate of the network on the amount and type of DLPEGDLDA copolymerized with the two different molecular weight ASCPs were examined in vitro. The networks degraded by bulk hydrolysis at a rate controlled primarily by the molecular weight of the ASCP used. Nevertheless, all the networks were completely degraded within 16 weeks. The MFFD was released in a diffusional manner at a rate influenced by the degree of swelling of the network and the molecular weight of the ASCP used; using an ASCP of a lower molecular weight for a given DLPEGDLDA resulted in a slower release rate. The degree of swelling of the networks was controlled solely by the nature of the PEG used in preparing the DLPEGDLDA, with greater swelling observed with higher PEG molecular weight and for greater amounts of PEG incorporation. The MFFD was not degraded during the photocrosslinking reaction or by potential acidic degradation products that may have accumulated within the device. This formulation provides a means of achieving a desirable release rate from a degradable, water-swellable network through selection of ASCP molecular weight and DLPEGDLDA composition.
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PMID:Anti-atherosclerotic peptide delivery from a photocrosslinkable biodegradable network. 2002 44

A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure-activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules.
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PMID:Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers. 2017 Jul 58

The noninvasive imaging of atherosclerotic plaques at an early stage of atherogenesis remains a major challenge for the evaluation of the pathologic state of patients at high risk of acute coronary syndromes. Recent studies have emphasized the importance of platelet-endothelial cell interactions in atherosclerosis-prone arteries at early stages, and the prominent role of P-selectin in the initial loose contact between platelets and diseased vessel walls. A specific MR contrast agent was developed here for the targeting, with high affinity, of P-selectin expressed in large amounts on activated platelets and endothelial cells. For this purpose, PEGylated dextran/iron oxide nanoparticles [PEG, poly(ethylene glycol)], named versatile ultrasmall superparamagnetic iron oxide (VUSPIO) particles, labeled with rhodamine were coupled to an anti-human P-selectin antibody (VH10). Flow cytometry and microscopy experiments on human activated platelets were highly correlated with MRI (performed at 4.7 and 0.2 T), with a 50% signal decrease in T(2) and T(1) values corresponding to the strong labeling of activated vs resting platelets. The number of 1000 VH10-VUSPIO nanoparticles attained per activated platelet appeared to be optimal for the detection of hypo- and hyper-signals in the platelet pellet on T(2) - and T(1) -weighted MRI. Furthermore, in vivo imaging of atherosclerotic plaques in ApoE mice at 4.7 T showed a spatial resolution adapted to the imaging of intimal thickening and a hypo-signal at 4.7 T, as a result of the accumulation of VH10-VUSPIO nanoparticles in the plaque. Our work provides support for the further assessment of the use of VH10-VUSPIO nanoparticles as a promising imaging modality able to identify the early stages of atherosclerosis with regard to the pertinence of both the target and the antibody-conjugated contrast agent used.
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PMID:MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. 2119 86

There remains a tremendous need to develop targeted therapeutics that can both image and localize the toxic effects of chemotherapeutics and antagonists on diseased tissue while reducing adverse systemic effects. These needs have fostered the development of a nanotechnology-based approach that can combine targeting and toxicity potential. In this study, CPMV nanoparticles were chemically modified with the dye Alexa Flour 488 and were also tandemly modified with PEG1000 followed by AF488; and the derivatized nanoparticles were subsequently added to macrophages stimulated with either LPS (M1) or IL-4 (M2). Previously published studies have shown that M1/M2 macrophages are both present in an inflammatory microenvironment (such as a tumor microenvironment and atherosclerosis) and play opposing yet balancing roles; M2 macrophages have a delayed and progressive onset in the tumor microenvironment (concomitant with an immunosuppression of M1 macrophages). In this study, we show higher uptake of CPMV-AF488 and CPMV-PEG-AF488 by M2 macrophages compared to M1 macrophages. M1 macrophages showed no uptake of CPMV-PEG-AF488. More specifically, M2 macrophages are known to be up-regulated in early atherosclerosis plaque. Indeed, previous work showed that M2 macrophages in plaque also correlate with CPMV internalization. These studies emphasize the potential effectiveness of CPMV as a tailored vehicle for targeting tumor macrophages involved in cancer metastasis or vascular inflammation and further highlight the potential of CPMV in targeted therapeutics against other diseases.
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PMID:Differential uptake of chemically modified cowpea mosaic virus nanoparticles in macrophage subpopulations present in inflammatory and tumor microenvironments. 2296 97


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