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)

Chlamydia pneumoniae may be involved in atherosclerosis by inducing inflammation as well as LDL oxidation. The transcription factor NF-kappa B is found in an active state in atherosclerotic lesions. This study examined the effect of C. pneumoniae exposure on the NF-kappa B system in human monocytic lineage cells. Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60 activated NF-kappa B, accompanied by increased cytokine production. Incubation with C. pneumoniae-induced depletion of I kappa B-alpha and later I kappa B-epsilon which was preceded by I kappa B kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C. pneumoniae induced NF-kappa B activation by preventing I kappa B phosphorylation/proteolysis. During long-term incubation with C. pneumoniae I kappa B-alpha returned to baseline, whereas the levels of I kappa B-epsilon and p65 were upregulated. Interestingly, long-term preincubation with C. pneumoniae selectively prevented restimulation by this microorganism, which appears to be at least partly facilitated by inhibition of I kappa B proteolysis. C. pneumoniae-induced NF-kappa B activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease.
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PMID:Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is inhibited by 4-HNE and following primary exposure. 1220 73

Amyloid-beta (Abeta) deposition in cerebral blood vessel walls is one of the key features of Alzheimer's disease (AD). Abeta(1-40) carrying the "Dutch" mutation (DAbeta(1-40)) induces rapid degeneration of cultured human brain pericytes (HBP). To study the mechanisms of this Abeta-induced toxicity, a comparative cDNA expression array was performed to detect differential gene expression of Abeta-treated versus untreated HBP. Messenger RNA expression of leukemia inhibitory factor (LIF) and insulin-like growth factor binding protein 3 (IGFBP-3) was increased in DAbeta(1-40)-treated HBP, whereas early growth response factor-1 (Egr-1) expression was decreased. Corresponding protein expression was investigated in AD and control brains. In all AD cases examined, LIF expression was observed in senile plaques and cerebral amyloid angiopathy, whereas IGFBP-3 expression in these lesions was only observed in a subset of cases. LIF and IGFBP-3 were also expressed in neurofibrillary tangles, as well as in neurons in AD and control brains. Egr-1 was predominantly expressed in astrocytes. Given its known involvement in both neuronal and immune responses to injury, the cytokine LIF may be a mediator of the inflammatory reaction seen in AD. IGFBP-3 is known to inhibit cell proliferation and induce apoptosis and may therefore contribute to neuronal degeneration in AD.
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PMID:Expression of the cytokine leukemia inhibitory factor and pro-apoptotic insulin-like growth factor binding protein-3 in Alzheimer's disease. 1241 Apr

E-selectin is a cytokine-inducible endothelial cell adhesion molecule that binds a restricted population of T lymphocytes consisting of Th1 memory cells bearing the cutaneous lymphocyte Ag (CLA). A serine to arginine (S128R) polymorphism in E-selectin has been reported at increased frequency in patients with systemic lupus erythematosus and atherosclerosis. Here we tested the hypothesis that the S128R substitution may contribute to increased vascular disease by altering the number and/or phenotype of lymphocytes interacting with E-selectin under shear flow. We observed that CHO cell monolayers transfected with S128R recruited significantly greater numbers of unfractionated lymphocytes than monolayers expressing an equivalent density of wild-type (WT) E-selectin. Depletion of the CLA(+) subpopulation or generation of CLA(-) lymphoblasts abolished rolling and arrest on WT E-selectin, but left a residual population that interacted with S128R. Generation of Th subsets revealed preferential interaction of Th0 and Th2, but not Th1, cells with S128R compared with WT. However, only T cells of a memory phenotype interacted with S128R, since neither monolayer supported rolling of CD45RA(+) cells. Our results demonstrate that the S128R polymorphism extends the range of lymphocytes recruited by E-selectin, which may provide a mechanistic link between this polymorphism and vascular inflammatory disease.
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PMID:Enhanced recruitment of Th2 and CLA-negative lymphocytes by the S128R polymorphism of E-selectin. 1242 68

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
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PMID:The role of the novel adipocyte-derived hormone adiponectin in human disease. 1261 9

The expression of cell adhesion molecules, P- and E-selectins, ICAM-1, and VCAM-1, was studied in cultured human vascular endothelial cells (ECs) infected by herpes simplex type I virus (HSV-1). It was shown that ECs without any signs of the cytopathogenic effect (CPE) expressed on their surface P- and E-selectins as soon as 24 h after infection. No appearance of VCAM-1 or increase in ICAM-1 expression was detected. Peripheral blood mononuclear cells (PBMCs) isolated by gradient centrifugation adhered preferentially with HSV-1-infected morphologically unchanged ECs but not with cells modified in result of CPE. The interferon and cytokine production by PBMCs was assayed after their contact with infected and glutaraldehyde-fixed ECs. The secretion of IFN-alpha, IFN-gamma, IL-1, IL-6, and TNF-alpha (but not of IL-4) was found to be inducible and correlated with the multiplicity of infection. Obtained results allow to consider a described cell culture system as a model for further investigation of initial stages of HSV-1 infection and of pathogenesis of vascular disease.
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PMID:Herpes Simplex Type I Virus Infection of Cultured Human Vascular Endothelial Cells: Expression of Cell Adhesion Molecules and Induction of Interferon and Cytokine Production by Blood Mononuclear Cells. 1268 35

For many years the classic model used for explaining the genesis of atheromatosis was that involving classic cardiovascular risk factors, caused either by a harmful life style or by hereditary alterations of the metabolism, principally dislipaemias. Recently we have learnt that, intimate molecular processes, as the inflammatory cytokine and cellular cascades, explain a great part of the vascular damage leading to the ischaemic episodes observed in the clinic. It can even be assessed, in general, the seric inflammation markers, as hypothetical tools for early diagnosis of vascular disease, are located on the physiopathological path between the classic risk factor (arterial hypertension, hypercholesterolaemia, obesity, diabetes) and the arterial lesion. This paper describes these inflammatory mechanisms, both from the viewpoint of basic science and from the viewpoint of its clinical role, and it also analyses the epidemiological value that these might have in the study of populations.
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PMID:[The inflammatory process of cardiovascular disease: new markers]. 1287 79

Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Atherogenesis begins with endothelial damage, and the damaged endothelium expresses adhesion molecules, chemokines, and proinflammatory cytokines that direct atherosclerotic plaque formation and spill into the circulation as biomarkers of atherosclerotic disease risk. Menopausal hormone therapy, including a variety of estrogen preparations with or without a progestin, has negative modulatory effects on most of these soluble inflammatory markers, including E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on transforming growth factor-beta, a vasoprotective cytokine. In contrast, 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. Although C-reactive protein is clearly linked to increased cardiovascular disease risk in women, the hormone-induced rise in this biomarker is not associated with increased risk and may be related to a first-pass effect of C-reactive protein production in the liver after oral estrogen absorption. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. Insights from fundamental mechanistic studies in animal models are needed to delineate the cellular/molecular events that determine whether these hormones protect or injure blood vessels.
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PMID:Hormone replacement therapy and inflammation: interactions in cardiovascular disease. 1291 55

The clinical coincidence of osteoporosis and vascular disease has long indicated that common mediators may adversely affect bone metabolism and vascular integrity alike. Receptor activator of NF-kappaB ligand (RANKL) is an important cytokine for bone resorption that acts through its osteoclastic receptor, receptor activator of NF-kappaB (RANK), while osteoprotegerin serves as a decoy receptor that binds RANKL and prevents activation of RANK. Skeletal and vascular cells are sources and targets of RANKL and OPG both in vitro and in vivo. Modulation of the RANKL/RANK/OPG system in animals results in a skeletal and vascular phenotype, and administration of OPG may prevent osteoporosis and vascular calcification. Recent studies on OPG serum levels and gene polymorphisms also suggest an important role of this cytokine system in skeletal and vascular diseases. In summary, there is increasing evidence that RANKL and OPG may link the skeletal with the vascular system.
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PMID:Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and vascular disease. 1452 2

Aortic vascular smooth muscle cells (VSMC) were used to study the effect of age on responses to high glucose concentrations or the cytokine, tumor necrosis factor-alpha (TNF-alpha). Activator protein-1 (AP-1) binding to DNA increased more in VSMC from old versus young rats (P < 0.02) and was related to increased expression of its components, c-Fos, Fra-1, and JunD. The relationship to upstream signals, i.e., activities of mitogen-activated protein kinases (MAPK), was studied using antibodies to total and phosphorylated forms of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. High glucose and TNF-alpha increased ERK phosphorylation more in old (P < 0.05); whereas only TNF-alpha induced JNK activation in young (P < 0.04). PD98059, a MEK inhibitor, attenuated AP-1 activation, lowered c-Fos and Fra-1 protein levels and reduced cell number and cells positive for proliferating cell nuclear antigen in old. We concluded that age differentially influenced activation of signaling pathways in VSMC exposed to high glucose or TNF-alpha. This may contribute to the increased risk for vascular disease associated with aging and diabetes mellitus (DM).
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PMID:Age-related differences in MAP kinase activity in VSMC in response to glucose or TNF-alpha. 1456 71

Estrogens play a vital role in the development of sexually dimorphic characteristics essential for reproduction. In recent years, insight has been gained into the role of estrogens in non-reproductive pathophysiological processes, including neoplasia, vascular disease and osteoporosis. Intriguingly, the skin appears to act as an end-organ target for estrogenic action; marked structural and functional skin changes occurring after the menopause can be related to altered hormonal profiles. One of the most important consequences of such hormonal changes is the age-related delay in cutaneous wound healing, leading to substantial morbidity and mortality, and increased costs to health services. Reduced estrogen levels have major downstream effects on cellular and tissue responses to injury; such downstream effects include impaired cytokine signal transduction, unchecked inflammation, and altered protein balance, and have a major impact on the rate of wound healing. Further understanding of the complex interaction between aging cells and the hormonal micro-environment is essential to develop focused therapeutic strategies to improve cutaneous wound healing in hypogonadal individuals, including the elderly.
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PMID:Potential role of estrogens in wound healing. 1457 96


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