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)

LIGHT is known to act as a novel mediator for atherogenesis. Furthermore, it has been reported that emodin, an active component extracted from rhubarb, can stop the growth of cancer cells. However, it is not known if emodin exerts anti-atherogenic effects in the human monocyte, THP-1, following treatment with LIGHT. In this study, we evaluated the inhibitory effect of emodin and rhein on LIGHT-induced migration in THP-1. Emodin and rhein decreased the level of LIGHT-induced generation of ROS, as well as the expression of CCR1, CCR2 and ICAM-1 and the production of IL-8, MCP-1, TNF-alpha, and IL-6. Emodin and rhein also decreased the phosphorylation of the p38 MAPK and IkB-alpha. Furthermore, the NADPH oxidase assembly inhibitor, AEBSF, and the blocker of NADPH oxidase, p47(phox) small interference RNA (siRNA), also efficiently blocked LIGHT-induced migration, CCR1, CCR2, ICAM-1, and HVEM expression, and p38 MAPK and NF-kB activation. These findings indicate that the inhibitory effects of emodin and rhein on LIGHT-induced migration occur via decreasing ROS production and NADPH oxidase p47(phox) activation. Taken together, these results indicate that emodin and rhein have the potential for use as an anti-atherosclerosis agent.
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PMID:Emodin and rhein inhibit LIGHT-induced monocytes migration by blocking of ROS production. 2029 10

Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.Key
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PMID:Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. 2031 85

Endothelin (ET) was first isolated and described by Yanagisawa et al. and has since been described as one of the most potent known vasoconstrictor compounds. ET-1 mediates its effects via two types of receptors, ETA and ETB, which are expressed in the vascular smooth muscle cells, endothelial cells, intestines and brain. Secretion of ET-1 results in long-lasting vasoconstriction, increased blood pressure and, in turn, overproduction of free radicals. As dysregulation of the endothelin system is an important factor in the pathogenesis of several diseases including atherosclerosis, hypertension and endotoxic shock, the ETA and ETB receptors are attractive therapeutic targets for treatment of these disorders. The biosynthesis and release of ET-1 are regulated at the transcriptional level. Studies have shown that p38MAP kinase, nuclear factor kappaB (NF-kappaB), PKC/ERK and JNK/c-Jun all take part in the ROS-activated production of ET-1. Furthermore, administration of ET(A) significantly reduces the generation of free radicals. However, treatment with ETB receptor blockers does not elicit the same effect. Therefore, the effects of endothelin receptor blockers on blood pressure and the generation of free radicals remain debatable. This review summarizes recent investigations into the role of endothelin receptor blockers with respect to the modulation of hemodynamic parameters and the generation of free radicals.
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PMID:Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress. 2036 Jun 13

Vascular inflammation process has been suggested to be an important risk factor in the initiation and development of atherosclerosis. In this study, we investigated whether and by what mechanisms an aqueous extract of Buddleja officinalis (ABO) inhibited the expressions of cellular adhesion molecules, which are relevant to inflammation and atherosclerosis. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ABO (1-10 microg/ml) for 18 hours dose-dependently inhibited TNF-alpha-induced adhesion U937 monocytic cells, as well as mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). Pretreatment with ABO also blocked TNF-alpha-induced ROS formation. Nuclear factor-kappa B (NF-kappaB) is required in the transcription of these adhesion molecule genes. Western blot analysis revealed that ABO inhibits the translocation of the p65 subunit of NF-kappaB to the nucleus. ABO inhibited the TNF-alpha-induced degradation of IkappaB-alpha, an inhibitor of NF-kappaB, by inhibiting the phosphorylation of IkappaB-alpha in HUVEC. Taken together, ABO could reduce cytokine-induced endothelial adhesiveness throughout down-regulating intracellular ROS production, NF-kappaB, and adhesion molecule expression in HUVEC, suggesting that the natural herb Buddleja officinalis may have potential implications in atherosclerosis.
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PMID:Anti-Inflammatory effect of Buddleja officinalis on vascular inflammation in human umbilical vein endothelial cells. 2050 74

GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H2O2 (hydrogen peroxide)-treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H2O2-treated cells in a dose-dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose-dependent manner in H2O2-treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 microM GSE, 2.0 microM TG (thapsigargin) and 20.0 microM 2-APB (2-aminoethoxydiphenyl borate) instead of 0.25 microM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p-AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up-regulation of eNOS and NO expression via inhibiting InsP3Rs (inositol 1,4,5-trisphosphate receptors)-mediated intracellular excessive calcium release and by activating p-AKT in endothelial cells.
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PMID:Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium. 2051 34

We hypothesized that the reciprocal association between adiponectin and lectin-like oxidized LDL (ox-LDL) receptor (LOX)-1 contributes to the regulation of aortic endothelial dysfunction in atherosclerosis. To test this hypothesis, endothelium-dependent (ACh) and endothelium-independent (sodium nitroprusside) vasorelaxation of isolated aortic rings from control mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE KO mice treated with either adiponectin (15 microg x day(-1) x mouse(-1) sc for 8 days) or neutralizing antibody to LOX-1 (anti-LOX-1, 16 microg/ml, 0.1 ml/mouse ip for 7 days) were examined. Although vasorelaxation to sodium nitroprusside was not different between control and ApoE KO mice, relaxation to ACh was impaired in ApoE KO mice. Adiponectin and anti-LOX-1 restored nitric oxide-mediated endothelium-dependent vasorelaxation in ApoE KO mice. Aortic ROS formation and ox-LDL uptake were increased in ApoE KO mice. Both adiponectin and anti-LOX-1 treatment reduced ROS production and aortic ox-LDL uptake. In mouse coronary artery endothelial cells, TNF-alpha incubation increased endothelial LOX-1 expression. Adiponectin reduced TNF-alpha-induced LOX-1 expression. Consistently, in ApoE KO mice, adiponectin treatment reversed elevated LOX-1 expression in aortas. Immunofluorescence staining showed that adiponectin was mainly colocalized with endothelial cells. Although adiponectin expression was lower in ApoE KO versus control mice, anti-LOX-1 increased aortic adiponectin expression, suggesting a reciprocal regulation between adiponectin and LOX-1. Moreover, both adiponectin and anti-LOX-1 reduced NF-kappaB expression in ApoE KO mice. Thus, adiponectin and LOX-1 may converge on NF-kappaB signaling to regulate their function. In conclusion, our results indicate that the reciprocal regulation between adiponectin and LOX-1 amplifies oxidative stress and ox-LDL uptake, leading to endothelial dysfunction in atherosclerosis.
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PMID:The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice. 2058 Oct 92

Increasing evidence suggests that lycopene may protect against atherosclerosis, although, the exact mechanism(s) is still unknown. Because lycopene is an efficient antioxidant, it has been proposed for a long time that this property may be responsible for its beneficial effects. Consistent with this, the carotenoid has been demonstrated to inhibit ROS production in vitro and to protect LDL from oxidation. However, recently, other mechanisms have been evoked and include: prevention of endothelial injury; modulation of lipid metabolism through a control of cholesterol synthesis and oxysterol toxic activities; reduction of inflammatory response through changes in cytokine production; inhibition of smooth muscle cell proliferation through regulation of molecular pathways involved in cell proliferation and apoptosis. Focusing on cell culture studies, this review summarizes the experimental evidence for a role of lycopene in the different phases of atherosclerotic process.
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PMID:Lycopene in atherosclerosis prevention: an integrated scheme of the potential mechanisms of action from cell culture studies. 2059 65

In recent years, the scientific community, food industry, consumers and media have revealed a growing interest regarding the potential benefits of tea consumption for human health. Several studies indicate that phenolic compounds, especially flavan-3-ols (catechins), are the main components responsible for the medicinal effects of this beverage due to their recognized antioxidant properties. Antioxidants are ascribed to reduce cells and biomolecules oxidative damage caused by reactive oxygen/nitrogen species (ROS/RNS). In fact, ROS and RNS have been implicated in the oxidative deterioration of food products, as well as in the pathogenesis of several chronic and/or ageing diseases such as atherosclerosis, diabetes mellitus, chronic inflammation, neurodegenerative disorders, including Alzheimer's disease, and certain types of cancer. (-)-Epigallocatechin-3-gallate, the main component of white and green teas, for which chemical synthesis is complex, not only possesses strong antiradicalar activity but also can inhibit nitration reactions, modulate carcinogen-metabolizing enzymes, trap ultimate carcinogens and inhibit cancer cell proliferation. The recent patents on the tea manufacture, extracts preparation and health-promoting properties are reviewed in this manuscript, especially in what concerns the chemopreventive and chemotherapeutic activities of tea polyphenols.
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PMID:Recent patents on Camellia sinensis: source of health promoting compounds. 2065 39

Pathophysiological studies have clearly demonstrated that the relationship between endothelial [dys]function and tissue ischemia is bidirectional: while it is well accepted that endothelial dysfunction has a key role in the progression and destabilization of coronary atherosclerosis, it is also well known that the endothelium is particularly sensitive to ischemia and reperfusion injury, and that this damage critically determines the extent of tissue damage, e.g. myocardial infarct size. Therefore, protecting the endothelium from ischemia could potentially have important clinical implications. In this scenario, reactive oxygen species [ROS] play a particularly important role: these elusive mediators are involved in determining the endothelial toxic effect of risk factors and are involved in reperfusion injury; however, most importantly, ROS are also key mediators of endothelial preconditioning, a protective process that is characterized by a reduced sensitivity to ischemia and reperfusion injury. We report considerations regarding these phenomena and their potential pharmacologic manipulation as discussed in a lecture at the recent Conference of the European Society of Clinical Hemorheology and Microcirculation held in Pontresina, Switzerland.
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PMID:Ischemic and non-ischemic preconditioning: Endothelium-focused translation into clinical practice. 2067 99

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose actions oppose those of angiotensin II (AngII). However, the underlying mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2 inhibited the development of early atherosclerotic lesions by suppressing the growth of vascular smooth muscle cells (VSMCs) and improving endothelial function. In a relatively large cohort animal study (66 rabbits), aortic segments transfected by Ad-ACE2 showed significantly attenuated fatty streak formation, neointimal macrophage infiltration, and alleviation of impaired endothelial function. Segments also showed decreased expression of monocyte chemoattractant protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and proliferating cell nuclear antigen, which led to the delayed onset of atherosclerotic lesions. At the cellular level, ACE2 significantly modulated AngII-induced growth and migration in human umbilical vein endothelial cells and VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK-p38, JAK-STAT, and AngII-ROS-NF-kappaB signaling pathways and up-regulation of the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could offer a therapeutic option for treating atherosclerosis.
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PMID:Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells. 2079 44


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