Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of vascular cells during inflammation is critical and is of particular importance in inflammatory diseases, including atherosclerosis, ischemia/reperfusion, and septic shock. Research in vascular biology has progressed remarkably in the last decade, resulting in a better understanding of the vascular cell responses to inflammatory stimuli. Most of the vascular inflammatory responses are mediated through the IkappaB/nuclear factor-kappaB system. Much recent work shows that vascular inflammation can be limited by anti-inflammatory counteregulatory mechanisms that maintain the integrity and homeostasis of the vascular wall. The anti-inflammatory mechanisms in the vascular wall involve anti-inflammatory external signals and intracellular mediators. The anti-inflammatory external signals include the anti-inflammatory cytokines, transforming growth factor-beta, interleukin-10 and interleukin-1 receptor antagonist, HDL, as well as some angiogenic and growth factors. Physiological laminar shear stress is of particular importance in protecting endothelial cells against inflammatory activation. Its effects are partly mediated through NO production. Finally, endogenous cytoprotective genes or nuclear receptors, such as the peroxisome proliferator-activated receptors, can be expressed by vascular cells in response to proinflammatory stimuli to limit the inflammatory process and the injury.
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PMID:Anti-inflammatory mechanisms in the vascular wall. 1134 96

The response of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), macrophage colony stimulating factor (MCSF), white blood cell (WBC), platelet (Plt), lactic acid (LAC) to cardiopulmnary bypass (CPB) were studied until 48 hours after aortic declamping in 11 patients who underwent elective CABG (n = 4), mitral valve plasty or replacement with modified maze procedure (n = 5), and both procedures (n = 2). The highest levels of the cytokines IL-6, IL-8, IL-10, and IL-1ra were observed after the removal of the cross clamp. These cytokines just after the aortic declamping are likely to be occurred not only by an interaction of the blood components with the artificial surfaces, but also by ischemia-reperfusion injury upon discontinuation of the aortic clamping. MCSF increased gradually in the late post-CPB phase and reached a peak at 48 hr after aortic declamping. MCSF may play an important role in regulating hematopoiesis on the postoperative days 1 and 2 in patients. In conclusion, the therapy based on the kinetics of these cytokines would be useful for patients undergoing CPB.
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PMID:[Serum cytokine levels response to cardiac surgery with cardiopulmonary bypass]. 1145 22

We have previously shown that deficiency in the anti-inflammatory cytokine interleukin-10 (IL-10) is responsible for enhanced angiogenesis after hindlimb ischemia. This study examined the putative involvement of matrix metalloproteinase (MMP) activation in this process. Ischemia was produced by artery femoral occlusion in both C57BL6 IL-10(+/+) and IL-10(-/-) mice. Angiographic vessel density and laser Doppler perfusion data at day 28 showed significant improvement in ischemic/nonischemic leg ratio by, respectively, 1.8-fold and 1.4-fold in IL-10(-/-) mice compared with IL-10(+/+) mice. This was associated with an increase in vascular endothelial growth factor (VEGF) protein content in the ischemic hindlimb. Three days after ischemia, gelatin zymography showed a significant increase in both pro- and active forms of MMP-2 and MMP-9 in ischemic hindlimbs of IL-10(-/-) mice compared with IL-10(+/+) mice (P<0.01). This increase in MMP activity in IL-10(-/-) mice was completely inhibited by treatment with BB-94 (5 mg/kg IP), a specific MMP inhibitor. Furthermore, increases in both vessel density and blood perfusion indexes at day 28 in IL-10(-/-) mice were abolished after treatment with BB-94 (0.78+/-0.06 versus 1.17+/-0.09 and 0.62+/-0.02 versus 0.88+/-0.04, for vessel density and blood perfusion ratio, respectively, in IL-10(-/-) mice treated with BB-94 versus untreated IL-10(-/-) mice, P<0.05). In contrast, BB-94 treatment did not affect the rise in VEGF protein content. These findings in IL-10(-/-) mice underscore the critical role of MMP activation, in a context of increased VEGF expression, in promoting ischemia-induced angiogenesis.
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PMID:Regulation of matrix metalloproteinase activity in ischemic tissue by interleukin-10: role in ischemia-induced angiogenesis. 1148 68

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients.
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PMID:Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients. 1180 50

Pharmacological strategies which limit neutrophil recruitment may also limit the damage induced by the reperfusion of an ischemic vascular territory. In the present study, we have investigated the effects of the BLT receptor antagonist, CP-105,696 ((+)-1-(3S,4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid), on the local, remote and systemic inflammatory changes observed during severe intestinal ischemia (120 min) and reperfusion (120 min) injury. The post-ischemic treatment with CP-105,696 (3 mg/kg) virtually abolished the increase in vascular permeability, but not neutrophil accumulation, in the intestine and lungs. CP-105,696 partially inhibited the reperfusion-induced neutropenia, but failed to affect intestinal haemorrhage or lethality. CP-105,696 had no inhibitory effect on the local and systemic increases in the concentrations of tumour necrosis factor (TNF-alpha), interleukin-1 beta and interleukin-10, but markedly suppressed interleukin-6. Overall, our results show that activation of BLT receptor plays a minor role in the local, remote and systemic injuries following severe ischemia and reperfusion in rats.
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PMID:Effect of a BLT receptor antagonist in a model of severe ischemia and reperfusion injury in the rat. 1195 89

Interleukin-10 markedly reduces production of proinflammatory cytokines by activated microglia or macrophages and downregulates the expression of activating molecules on these cells. In studies performed in adults or in cell cultures, interleukin-10 protected against hypoxic-ischemic neuronal death and against lipopolysaccharide-mediated oligodendrocyte cell death. Furthermore, it was recently shown that interleukin-10 counteracts metabolic and microcirculatory effects of hypoxia-ischemia in the perinatal pig brain. Intracerebral injection of the glutamatergic analogue ibotenate to newborn mice induces cortical plate and white matter lesions mimicking the brain damage associated with cerebral palsy, and pretreatment with proinflammatory cytokines such as interleukin-1-beta or with interleukin-9 significantly exacerbates these lesions. The present study evaluated the influence of interleukin-10 on ibotenate-induced brain lesions in newborn mice under basal conditions or after exposure to cytokines. Intraperitoneal injection of interleukin-10 for 3 days following ibotenate significantly reduced the size of excitotoxic brain lesions. Intraperitoneal injection of neutralizing anti-interleukin-10 antibody for 3 days following ibotenate had no detectable effect and no difference in ibotenate-induced brain lesion size was found between wild type pups and pups deleted for the interleukin-10 gene, suggesting that endogenous interleukin-10 in newborn mice may have limited effects. Co-administration of intracerebral ibotenate and interleukin-10 had no detectable effect, arguing against a direct neuroprotective effect of interleukin-10 on neurons. While pretreatment with intraperitoneal interleukin-10 alone had no detectable effect on excitotoxic brain lesions, interleukin-10 given with interleukin-1-beta pretreatment blunted the toxic effects of interleukin-1-beta. On the other hand, combined pretreatment with IL-9 and anti-IL-10 antibody largely reversed the exacerbating effect of IL-9 on excitotoxic brain lesions. Altogether, these data suggest that, in newborn mice, exogenous interleukin-10 can be neuroprotective when acting in an inflammatory context.
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PMID:Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. 1264 45

The effects of Kupffer cells on cytokine responses in endotoxin-enhanced reperfusion injury after total hepatic ischemia were investigated in this study. Male rats pretreated with either normal saline solution (NS group) or gadolinium chloride (GdCl(3)) to inhibit Kupffer cell function (GC group) were subjected to 60 min of hepatic ischemia. These animals received either normal saline solution or sublethal doses of endotoxin (1 mg/kg) at reperfusion. In the NS group, endotoxin administration induced an enhanced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 production 1 h after reperfusion with a subsequent peak of macrophage inflammatory protein-2 (MIP-2) levels, which resulted in a 7-day survival rate of 30%. Despite endotoxin administration, GdCl(3) pretreatment significantly suppressed TNF-alpha and increased interleukin-10 production 1 h after reperfusion, which led to a decline in MIP-2 production and amelioration of functional and structural liver damage with a 7-day survival rate of 80%. Augmented pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells were associated with endotoxin-enhanced reperfusion injury after hepatic ischemia. Kupffer cell blockade has a potential to attenuate the insult via modulation of cytokine responses.
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PMID:Regulation of pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells in endotoxin-enhanced reperfusion injury after total hepatic ischemia. 1273 Aug 3

Heme oxygenase (HO)-1 catabolizes heme into three products: carbon monoxide (CO), biliverdin (which is rapidly converted to bilirubin) and free iron (which leads to the induction of ferritin, an iron-binding protein). HO-1 serves as a "protective" gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. Administration of CO, biliverdin, bilirubin or iron-binding compounds is protective in rodent disease models of ischemia-reperfusion injury, allograft and xenograft survival, intimal hyperplasia following balloon injury or as seen in chronic graft rejection and others. We suggest that the products of HO-1 action could be valuable therapeutic agents and speculate that HO-1 functions as a "therapeutic funnel", mediating the beneficial effects attributed to other molecules, such as interleukin-10 (IL-10), inducible nitric oxide synthase (NOS2; iNOS) and prostaglandins. This Review is the third in a series on the regulation of the immune system by metabolic pathways.
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PMID:Heme oxygenase-1: unleashing the protective properties of heme. 1290 59

This review discusses the myocardial protective property of the insulin/glucose-insulin-potassium regimen and the mechanisms involved in this beneficial action. Several recent studies suggest that insulin not only is useful to control hyperglycemia and maintain glucose homeostasis but also may have the unique property to protect the myocardium from reperfusion injury and ischemia and prevent apoptosis of myocardial cells. The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10. Thus, the insulin/GIK regimen brings about its cardioprotective action. This may also explain why the insulin/GIK regimen is useful in sepsis and septic shock, myocardial recovery in acute myocardial infarction, and critical illness. It is suggested that the infusion of adequate amounts of insulin to patients with acute myocardial infarction, congestive heart failure, cardiogenic shock, and critical illness preserves myocardial integrity and function and ensures rapid recovery. In view of the suppressive action of insulin on the synthesis of proinflammatory cytokines and free radicals, it is possible that the insulin/GIK regimen, when used in a timely and appropriate fashion, may also protect other tissues and organs and facilitate in the recovery of patients who are critically ill.
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PMID:Insulin: an endogenous cardioprotector. 1450 50

The ependyma is one of the feasible targets for gene transfer to the brain. Using two different replication-deficient recombinant adenoviral vectors, AdCMVbetaGal or AdRSVIL10, we examined effects of cortical brain ischemia on transgene expression in the ependyma after administration of the vector into the lateral ventricle of spontaneously hypertensive rats (SHR). Expression of the reporter gene lacZ at the lateral ventricle was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis. Ependymal cells in the ventricles expressed the transgene as early as 6 h after gene transfer in both sham treatment and ischemia treatment. In the sham treatment, the expression peaked at 12 h and slowly decreased toward day 4 and day 7. However, transgene expressions in the ischemic brain on day 4 and day 7 were significantly higher than sham treatment. In the biochemical assay, beta-galactosidase activity detected on day 4 at the periventricular area of the ischemic group (37 +/- 9 mU/mg protein) was significantly greater than that of the sham group (12 +/- 4, P < 0.01). In the enzyme-linked immunosorbent assay for gene transfer of interleukin-10 (IL-10), IL-10 in the cerebrospinal fluid (CSF) of the ischemic group (11,633 +/- 4322 pg/ml) was significantly greater than that in the sham group (2460 +/- 1486, P < 0.05) on day 5. These results suggest that transgene expression in the exo-focal remote area of ependyma is augmented by cortical ischemia, and the ependyma may be a promising target of gene transfer of brain ischemia.
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PMID:Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats. 1476 82


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