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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the advent of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has declined substantially, and cardiovascular, liver, and renal diseases have emerged as major causes of morbidity and mortality in individuals with human immunodeficiency virus (HIV). Acute renal failure is common in HIV-infected patients and is associated with acute infection and medication-related nephrotoxicity. HIV-associated nephropathy is the most common cause of chronic kidney disease in HIV-positive African American populations and may respond to HAART. Other important HIV-associated renal diseases include HIV immune complex kidney diseases and thrombotic microangiopathy. The increasing importance of non-HIV-associated diseases, such as diabetes mellitus, hypertension, and vascular disease, to the burden of chronic kidney disease has been recognized, focusing attention on prevention and control of these diseases in HIV-positive individuals. HIV-positive individuals who experience progression to end-stage renal disease and who have undetectable HIV-1 viral loads while receiving HAART should be evaluated for renal transplant. Emerging evidence suggests that HIV-positive individuals may have graft and patient survival comparable to HIV-negative individuals. Several studies suggest that HIV-1 can potentially infect renal cells, and HIV transgenic mice have clarified the roles of a number of HIV proteins in the pathogenesis of HIV-associated renal disease. Host factors may modify disease expression at the level of cytokine networks and the renal microvasculature and contribute to the pathogenic effects of HIV-1 infection on the kidney.
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PMID:HIV-1 infection and the kidney: an evolving challenge in HIV medicine. 1780 78

Adipose tissue expresses cytokines which inhibit insulin signalling pathways. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We have previously suggested that adipocytokines might contribute to the coexistence of insulin resistance and endothelial dysfunction. However, the adipocytokine best characterised as causing insulin resistance is tumour necrosis factor-alpha (TNF-alpha), a molecule which under normal circumstances circulates in low concentrations. We propose a vasoregulatory role for local deposits of fat around blood vessels, which may contribute both to insulin action and to vascular endothelial dysfunction. In particular, we propose that the localised fat depot around the origin of skeletal muscle arterioles may play a physiological role in blood flow distribution. Isolated rat arterioles are under dual regulation by insulin, which activates both endothelin-1 mediated vasoconstriction and nitric oxide mediated vasodilatation. In obese rat arterioles, insulin-stimulated nitric oxide synthesis is impaired, resulting in unopposed vasoconstriction. We propose this to be the consequence of production of TNF-alpha from the fat surrounding the vessel origin - a depot to which we ascribe a specialist vasoregulatory role. We suggest that this cytokine accesses the nutritive vascular tree to inhibit insulin-mediated capillary recruitment - a mechanism we term 'vasocrine' signalling. We also suggest a homology between periarteriolar fat and both periarterial and visceral fat, which may, through outside-to-inside signalling, play a direct role in producing the inflammatory changes found in atherosclerotic plaques, so explaining relationships between visceral fat, insulin resistance, and vascular disease.
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PMID:Inflammation, obesity, and the metabolic syndrome. 1795 30

Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and memory impairment in transgenic mouse models of Alzheimer's disease (AD). Active Abeta immunization has also yielded favorable results in a subset of AD patients. However, a small percentage of patients developed severe aseptic meningoencephalitis associated with brain inflammation and infiltration of T-cells. We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates Abeta-induced inflammatory responses and enhances Abeta clearance. Here, we utilized genetic and pharmacologic approaches to test whether CD40-CD40L blockade could enhance the efficacy of Abeta(1-42) immunization, while limiting potentially damaging inflammatory responses. We show that genetic or pharmacologic interruption of the CD40-CD40L interaction enhanced Abeta(1-42) immunization efficacy to reduce cerebral amyloidosis in the PSAPP and Tg2576 mouse models of AD. Potentially deleterious pro-inflammatory immune responses, cerebral amyloid angiopathy (CAA) and cerebral microhemorrhage were reduced or absent in these combined approaches. Pharmacologic blockade of CD40L decreased T-cell neurotoxicity to Abeta-producing neurons. Further reduction of cerebral amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from brain to blood, but was rather correlated with anti-inflammatory cytokine profiles and reduced plasma soluble CD40L. These results suggest CD40-CD40L blockade promotes anti-inflammatory cellular immune responses, likely resulting in promotion of microglial phagocytic activity and Abeta clearance without generation of neurotoxic Abeta-reactive T-cells. Thus, combined approaches of Abeta immunotherapy and CD40-CD40L blockade may provide for a safer and more effective Abeta vaccine.
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PMID:CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation. 1805 9

Interferon-alpha and ribavirin are widely used treatments for chronic hepatitis C. It is believed to be a cytokine made by T lymphocytes upon activation by foreign antigens. Complications of interferon and ribavirin therapy include systemic flulike symptoms, marrow suppression, emotional liability, auto immune reactions (especially auto immune thyroiditis) and miscellaneous side effects such as alopecia, rashes, diarrhea, numbness, and tingling of the extremities. With the possible exception of autoimmune thyroiditis, all these side effects are reversed upon dose lowering or cessation of therapy. We report a case of a 51-year-old man, with no previous history of vascular disease, who developed ischemic colitis after interferon-alpha and ribavirin therapy for chronic hepatitis C. In the literature, there have been only 2 published accounts associating interferon-alpha use with ischemic colitis in 2 patients. This report illustrates a better association of interferon-alpha and ribavirin with ischemic colitis.
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PMID:Interferon-ribavirin-associated ischemic colitis. 1822 89

The cytokine macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory regulator of many acute and chronic inflammatory diseases. In the pathogenesis of atherosclerosis, chronic inflammation of the arterial wall characterized by chemokine-mediated influx of leukocytes plays a central role. The contribution of MIF to atherosclerotic vascular disease has come into focus of many studies in recent years. MIF is highly expressed in macrophages and endothelial cells of different types of atherosclerotic plaques, and functional studies established the contribution of MIF to lesion progression and plaque inflammation. This proatherogenic effect may partly be explained by the finding that MIF regulates inflammatory cell recruitment to lesion areas. Similar to chemokines, MIF induces integrin-dependent arrest and transmigration of monocytes and T cells. These chemokine-like functions are mediated through interaction of MIF with the chemokine receptors CXCR2 and CXCR4 as a non-canonical ligand. In atherogenic monocyte recruitment, MIF-induced monocyte adhesion involves CD74 and CXCR2, which form a signaling receptor complex. In addition to lesion progression, MIF has been implicated in plaque destabilization, since MIF is predominantly expressed in vulnerable plaques and can induce collagen-degrading matrix metalloproteinases. The latter could be a relevant mechanism in atherosclerotic abdominal aneurysm formation, where MIF expression is correlated with aneurysmal expansion. In summary, MIF has been identified as an important regulator of atherosclerotic vascular disease with exceptional chemokine-like functions. Detailed analysis of the interaction of MIF with its receptors could provide valuable information for drug development for the anti-inflammatory treatment of established and unstable atherosclerosis.
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PMID:Chemokine-like functions of MIF in atherosclerosis. 1838 67

Impaired wound healing in diabetes is a significant clinical problem which is thought to be associated with neuropathy and angiopathy previously . The present study indicates that accumulation of glucose and glycometabolic products in skin tissue, as the result of glycometabolic disorders, which contributes to cutaneous environmental alterations in diabetes mellitus, and subsequently induces the abnormal cell behaviors, cytokine alteration and matrix modification. Thus, diabetic neuropathy and angiopathy might be regarded as the pathological outcome of cutaneous environmental alterations. In conclusion, glycometabolism disorders could be described as one of the initial events for the alteration involving in the underlying cutaneous disorder which impair healing process. The related research focuses on the initial event of controlling disorders in wound healing and therefore contribute to providing the strategy of treatment as based on these approaches.
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PMID:[A potential mechanism for impaired wound healing--cutaneous environmental disorders in diabetes mellitus]. 1851 49

Interleukin-18 (IL-18), a product of dendritic cells (DC), is a pro-inflammatory cytokine involved in the pathogenesis of allograft rejection, vascular disease, arthritis and diabetes. Rapamycin (Rapa) is an immunosuppressant that inhibits T cell mTOR kinase activation. In contrast, Sanglifehrin A (SFA), is a cyclophilin-binding immunosuppressant that does not act on calcineurin phosphatases but appears to inhibit IL-2-dependent T cell proliferation. Rapa and SFA exert some immunosuppressive effects on DC by inhibiting IL-12 production, although their effects on DC have not been investigated as comprehensively as those on T cells. We aimed to determine the impact of these drugs on DC IL-18 synthesis in vivo and in vitro. We found in vivo that LPS-stimulated OX62(+) DC produced significantly more IL-18 mRNA, compared to OX62(+) DC depleted splenocytes (p<0.01) and non-LPS-stimulated OX62(+) DC (p<0.01). OX62(+)CD4(+) and OX62(+)CD4(-) cells produced similar amounts of IL-18 mRNA. Rapa and SFA, but not CsA, significantly inhibited IL-18 production from OX62(+) DC in vitro, in a dose-dependent manner (p<0.05). In vivo IL-18 production was also inhibited by Rapa and SFA in splenic OX62(+) DC (p<0.01). Finally, inhibition of IL-18 production by Rapa and SFA was independent of the FK506 or cyclophilin pathways, respectively. In conclusion, Rapa and SFA, but not CsA, block IL-18 production and this novel Rapa blockade effect on IL-18 may contribute to the ability of Rapa to inhibit chronic allograft nephropathy and restenosis.
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PMID:Dentritic cell derived IL-18 production is inhibited by rapamycin and sanglifehrin A, but not cyclosporine A. 1866 82

Anti-inflammatory cytokines may play a protective role in the progression of vascular disease. The purpose of this study was to characterize interleukin (IL)-19 expression and function in the development of intimal hyperplasia, and discern a potential mechanism of its direct effects on vascular smooth muscle cells (VSMCs). IL-19 is an immunomodulatory cytokine, the expression of which is reported to be restricted to inflammatory cells. In the present study, we found that IL-19 is not expressed in quiescent VSMCs or normal arteries but is induced in human arteries by injury and in cultured human VSMCs by inflammatory cytokines. Recombinant IL-19 significantly reduced VSMC proliferation (37.1 +/- 4.8 x 10(3) versus 72.2 +/- 6.1 x 10(3) cells/cm(2)) in a dose-dependent manner. IL-19 adenoviral gene transfer significantly reduced proliferation and neointimal formation in balloon angioplasty-injured rat carotid arteries (0.172 +/- 29.9, versus 0.333 +/- 71.9, and 0.309 +/- 56.6 microm(2)). IL-19 induced activation of STAT3 as well as the expression of the suppressor of cytokine signaling 5 (SOCS5) in VSMCs. IL-19 treatment significantly reduced the activation of p44/42 and p38 MAPKs in stimulated VSMCs. Additionally, SOCS5 was found to interact with both p44/42 and p38 MAPKs in IL-19-treated human VSMCs. This is the first description of the expression of both IL-19 and SOCS5 in VSMCs and of the functional interaction between SOCS5 and MAPKs. We propose that through induction of SOCS5 and inhibition of signal transduction, IL-19 expression in VSMCs may represent a novel, protective, autocrine response of VSMCs to inflammatory stimuli.
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PMID:Expression and suppressive effects of interleukin-19 on vascular smooth muscle cell pathophysiology and development of intimal hyperplasia. 1866 13

Tubulointerstitial fibrosis is an integral part of the structural changes of the kidney in chronic progressive renal failure. The accumulation of the extracellular matrix in the tubulointerstitial space is mediated mainly by myofibroblasts. These are derived from resident interstitial fibroblasts, tubular epithelial cells, periadventitial cells, and possibly also mesenchymal stem cells and endothelial cells. Fibrosis is usually preceded by tubulointerstitial infiltration of mononuclear inflammatory cells. Proteinuria is one of several mechanisms of primary glomerular or vascular disease to transmit the disease process to the interstitial space. Increased protein filtration may have direct toxic effects on tubular epithelial cells, induce chemokine and cytokine secretion and result in increased expression of adhesion molecules, all contributing to the influx of mononuclear cells. Inflammatory cells in return secrete cytokines, which stimulate resident fibroblasts and tubular epithelial cells to differentiate into matrix-producing cells. The phenotypic conversion of primary epithelial cells into mesenchymal cells, termed epithelial-mesenchymal transition (EMT), has been studied in great detail in recent years. Several signal transduction pathways of this process have been clarified and may eventually result in novel therapeutic approaches. The severity of proteinuria and the extent of EMT have both been associated with the decline in renal function in clinical studies. Limiting proteinuria results in a slower decline of renal function deterioration, whereas reducing EMT has had beneficial effects in a number of animal studies, including those indicating reversal of fibrotic lesions. However, the association between proteinuria and EMT and vice versa is far from clear and has not been carefully studied.
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PMID:EMT and proteinuria as progression factors. 1871 3

Graft vascular disease (GVD) is the single most important long-term limitation to solid-organ transplantation. It is a concentric vascular intimal hyperplastic lesion composed of smooth muscle-like cells and associated matrix. GVD diffusely involves allograft vessels, eventually compromising perfusion and resulting in graft ischemia and failure. Animal models and an increasing sophistication in analyzing human GVD have provided important new insights into GVD pathogenesis. Innate and specific immune responses both participate in the initial vascular injury; GVD develops as a consequence of downstream chemokine- and cytokine-effector pathways. Other significant developments in the field include recognition of the central pathogenic role played by interferon-gamma as well as the contribution of host cell precursors to the intimal lesions. Because GVD shares many features with more common vascular pathologies, insights gleaned from our understanding of allograft vasculopathy may well impact our treatment for "traditional" atherosclerosis or restenosis lesions.
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PMID:Graft vascular disease: immune response meets the vessel wall. 1871 41


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