Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In diabetes mellitus an increased risk exists for vascular complications. A role for advanced glycation endproducts (AGEs) in the acceleration of vascular disease has been suggested. Nepsilon-(carboxymethyl)lysine (CML)- and methylglyoxal (MGO)-modified proteins have been identified as major AGEs. The interaction of these AGEs with the human endothelial cells and macrophages was studied. Changes in adhesion molecule expression, i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by cell-bound Elisa on human endothelial cells after incubation with CML-modified albumin and MGO-modified albumin. The presence of the full-length receptor of AGEs (RAGE) and splice variants of RAGE was determined by specific RT-PCR. In addition, binding studies were performed with CML- and MGO-modified albumin to endothelial cells and P388D1 macrophages. We demonstrated that CML-albumin or MGO-albumin did not induce activation of endothelial cells as measured by the expression of adhesion molecules, while, under the same conditions, TNF-alpha did. No specific binding of CML-albumin and MGO-albumin on these cells was found. In contrast to endothelial cells, a specific binding of MGO-albumin to P388D1 macrophages was demonstrated, which could be competed by ligands of scavenger receptors. In human umbilical vein and microvascular endothelial cells we found the N-truncated and C-truncated splice variants of RAGE. In conclusion, under our experimental conditions no CML- or MGO-albumin-induced increase in adhesion molecule expression was found on endothelial cells. In agreement with this, no binding of these AGEs was found to endothelial cells. The existence of splice variants of RAGE in endothelial cells might explain the lack of interaction of extracellular AGEs with these cells.
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PMID:Interaction of Nepsilon(carboxymethyl)lysine- and methylglyoxal-modified albumin with endothelial cells and macrophages. Splice variants of RAGE may limit the responsiveness of human endothelial cells to AGEs. 1649 95

Honokiol, a compound extracted from Chinese medicinal herb Magnolia officinalis, has several biological effects. However, its protective effects against endothelial injury remain unclarified. In this study, we examined whether honokiol prevented oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial dysfunction. Incubation of oxLDL with honokiol (2.5-20 microM) inhibited copper-induced oxidative modification as demonstrated by diene formation, thiobarbituric acid reactive substances (TBARS) assay and electrophoretic mobility assay. Expression of adhesion molecules (ICAM, VCAM and E-selectin) and endothelial NO synthase (eNOS) affected by oxLDL was investigated by flow cytometry and Western blot. We also measured the production of reactive oxygen species (ROS) using the fluorescent probe 2',7'-dichlorofluorescein acetoxymethyl ester (DCF-AM). Furthermore, several apoptotic phenomena including increased cytosolic calcium, alteration of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 were also investigated. Apoptotic cell death was characterized by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. The results showed that honokiol prevented the copper-induced oxidative modification of LDL. Honokiol also ameliorated the oxLDL-diminished eNOS protein expression and reduced the oxLDL-induced adhesion molecules and the adherence of THP-1 cells to HUVECs. Furthermore, honokiol attenuated the oxLDL-induced cytotoxicity, apoptotic features, ROS generation, intracellular calcium accumulation and the subsequent mitochondrial membrane potential collapse, cytochrome c release and activation of caspase-3. Our results suggest that honokiol may have clinical implications in the prevention of atherosclerotic vascular disease.
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PMID:Protective effects of honokiol against oxidized LDL-induced cytotoxicity and adhesion molecule expression in endothelial cells. 1658 Jun 56

Imaging of endothelial-specific markers is critically important in non-invasive detection of early signs of vascular pathologies (eg inflammation, atherosclerosis and angiogenesis). A model of adoptive human endothelial cell (HUVEC) transfer was used to test-specific imaging probes for human vascular disease consisting of cross-linked iron oxide (CLIO) nanoparticles conjugated to anti-human E-selectin (CLIO-F(ab')(2)). To perform in vivo imaging of E-selectin expression in functional blood vessels, human vascular endothelium cells (HUVECs) were implanted in athymic mice in Matrigel solution, which served as a temporary neovascularization scaffold after the solidification. The formation of HUVEC-containing vessels was established by histology and microscopy. CLIO-F(ab')(2) probes were administered via an i.v. injection following the induction of E-selectin expression by IL-1beta. High-resolution MR images were obtained before and after the administration of CLIO-F(ab')(2), which showed specific hypointensity only if treated with IL-1beta. A three-times higher CLIO-induced MR signal decrease on T2(*) images was measured in HUVEC implants in response to IL-1beta treatment. Image signal intensity did not change in control animals that: (1) harbored Matrigel alone, (2) in the absence of IL-1beta treatment or (3) in animals injected with CLIO linked to the idiotype-matched control F(ab')(2). Experiments in an adoptive transfer model demonstrated that HUVEC-containing neovessels are perfused and that IL-1beta inducible E-selectin expression in these vessels is detectable with non-invasive imaging by using targeted nanoparticles.
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PMID:Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. 1660 78

AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in regulation of energy homeostasis and metabolic stress. Metformin has been shown to activate AMPK. We hypothesized that metformin may prevent nuclear factor kappaB (NF-kappaB) activation in endothelial cells exposed to inflammatory cytokines. Metformin was observed to activate AMPK, as well as its downstream target, phosphoacetyl coenzyme A carboxylase, in human umbilical vein endothelial cells (HUVECs). Metformin also dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF-alpha-induced IkappaB kinase activity. Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), dose-dependently inhibited TNF-alpha- and interleukin-1beta-induced NF-kappaB reporter gene expression. AICAR also suppressed the TNF-alpha- and interleukin-1beta-induced gene expression of vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 in HUVECs. The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation. In light of these findings, we suggest that metformin attenuates the cytokine-induced expression of proinflammatory and adhesion molecule genes by inhibiting NF-kappaB activation via AMPK activation. Thus, it might be useful to target AMPK signaling in future efforts to prevent atherogenic and inflammatory vascular disease.
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PMID:Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. 1663 95

Highly active antiretroviral therapy (HAART) has greatly reduced the risk of early death from opportunistic infections and extended the lifespan of people infected with the human immunodeficiency virus (HIV). Thus, many complications and organic damage in the HIV-infected population emerge. Cardiovascular disease as coronary artery disease has become a matter of particular concern. Its incidence is greatly increased in the HIV-infected population over that of people of the same age in the absence of general cardiovascular risk factors. Despite several clinical and laboratory studies in the association between HIV infection and cardiovascular disease, the pathogenic mechanisms of this significant clinical problem are largely unknown and are now under active investigation. Endothelial dysfunction is possibly the most plausible link between HIV infection and atherosclerosis. Increased expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and endothelial adhesion molecule (E-selectin) and inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL-6 has been reported in HIV-positive patients. The effect of HAART on endothelial function in HIV-positive patients is also demonstrated. In this review, we focus on the recent research update of HIV-associated vascular disease and vascular injury. We analyze and discuss the recent clinical and laboratory investigations on the effect of HIV, viral protein, and HAART therapy on endothelial injury and vascular disease; identify the areas of controversy and clinical relevance; and suggest some directions for future research.
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PMID:Current update on HIV-associated vascular disease and endothelial dysfunction. 1737 67

The aim of this chapter is to present and identify potential pharmacological targets in endothelial cell-monocyte interactions leading to vascular syndrome and involving inflammation, coagulation, vascular remodelling and thrombosis. Increasing evidence is indicating that endothelial cells play a key role in atherothombosis by their capacity to attract, bind and allow the extravasation of monocytes to sites of inflammation. Surface expression and/or activation of constituent cell adhesion molecules (for e.g. P-selectin, E-selectin, ICAM-1, and VCAM-1) on endothelial cells together with chemokines such as CXCL8 (IL-8), Platelet-activating factor (PAF), CCL2 and CCL5 (Table 1) allow the rolling, adhesion and extravasation of monocytes. This review focuses on pharmacological targets implicated in endothelial cells interactions with monocytes/macrophages in vascular disease states and on cutting edge genomic tools for the identification and characterization of such targets.
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PMID:The dialogue between endothelial cells and monocytes/macrophages in vascular syndromes. 1758 5

Adiponectin (APN) is an adipocyte-derived factor that exists at high concentrations in serum and has anti-inflammatory and systemic vascular-protective properties. In this study, we investigated the role of APN in pulmonary vascular homeostasis. We found that APN localizes to the luminal side of blood vessels in lung and acts in vitro to block TNF-alpha-induced E-selectin upregulation in pulmonary artery endothelial cells. Targeted deletion of the APN gene in mice leads to a vascular phenotype in lung characterized by E-selectin upregulation and age-dependent increases in perivascular inflammatory cell infiltration and pulmonary arterial pressures. Taken together, these findings demonstrate an important role for APN in lung vascular homeostasis and suggest that APN-deficient states may contribute to the pathogenesis of inflammatory pulmonary vascular disease and to the development of pulmonary hypertension.
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PMID:Adiponectin deficiency: a model of pulmonary hypertension associated with pulmonary vascular disease. 1956 Nov 37

Cardiovascular disease is the leading cause of death among women. Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Women present with cardiovascular disease a decade after men and this has been attributed to the protective effect of female ovarian sex hormones. Hormone replacement therapy (HRT), including a variety of estrogen preparations with or without a progestin, has negative effects on most of these soluble inflammatory markers, including E-selectin, cell adhesion molecules, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on vasoprotective cytokine, such as the transforming growth factor-alpha. C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Animal and observational studies have shown beneficial effects of hormone therapy in the perimenopausal period or before the development of significant atherosclerosis, whereas randomized trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. This review outlines the effects of HRT on inflammatory biomarkers, summarizes results from observational and randomized trials, and highlights unanswered questions of hormone therapy and cardiovascular risk.
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PMID:Effect of hormone replacement therapy on inflammatory biomarkers. 1963 77

Pregestational diabetes with vasculopathy in pregnant women is still associated with increased risk for severe maternal and foetal complications and their pathomechanism remains unclear. We investigate endothelial function in diabetic pregnant women with and without vascular disease, measured as changes in concentrations of soluble E-selectin and VCAM-1 throughout pregnancy. 121 pregnant women with PGDM and singleton pregnancy (30 participants with vasculopathy, 91 without vasculopathy) were enrolled into the prospective study. Control group consisted of 20 nondiabetic pregnant women in uncomplicated gestation, sampled cross-sectionally in early pregnancy and at term. We demonstrated lower concentrations of circulating sE-selectin both in early and in late diabetic gestation, irrespective of a concomitant vasculopathy. We also found reduced concentrations of sVCAM-1 in late gestation in diabetic pregnancies both with and without vascular disease, and reduced increase in its levels with gestation. We report significantly elevated concentrations of sVCAM-1 in early pregnancy in diabetic participants with retinopathy and nephropathy comparing with patients with retinopathy only and nondiabetic pregnant controls. We noted a general pattern of pregestational diabetes associated with reduced levels of cell adhesion molecules in early pregnancy with a further reduction during gestation, except for participants with combined retino- and nephropathy.
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PMID:Microvascular complications are associated with low levels of maternal sE-selectin and sVCAM-1 in pregnancy complicated with pregestational diabetes mellitus. 2012 88

Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45-84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p=0.008 and p=0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p=0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.
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PMID:Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: the MESA-RV Study. 2092 24


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