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)

Platelets are known to contribute to ischemia/reperfusion in several organs, but their role in inflammation and organ injury after hemorrhagic shock (HS) has not been examined. To address this issue, we rendered mice thrombocytopenic (20% of normal platelet count) by treatment with pOp3, a rat monoclonal antibody against platelet glycoprotein Ibalpha, 24 h before subjecting them to either a standard HS or sham protocol. Liver apoptosis increased 3- to 5-fold (P<0.05), and focal liver necrosis increased 11-fold (P<0.01) in placebo-treated shock mice compared with sham; these increased indices of liver injury were completely prevented by pOp3 pretreatment. Neutrophils infiltrating the liver increased nearly 3-fold in placebo-treated shock mice versus sham (P<0.05); this shock-induced increase in neutrophil infiltration was also eliminated by pretreatment with pOp3. Alveolar cross-sectional area, used to histologically assess interstitial lung edema and cellular infiltration, was reduced by 25% in pOp3-treated shock mice versus placebo-treated shock mice (P<0.05). Similar to the results in liver, pOp3 pretreatment decreased neutrophil infiltration in the lung after HS. Thus, platelets contribute to the inflammatory injuries of the liver and lung after HS, in part, perhaps by facilitating neutrophil infiltration into tissues.
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PMID:Essential role for platelets in organ injury and inflammation in resuscitated hemorrhagic shock. 1698 Aug 86

Acute coronary syndromes (ACS) are frequent in the elderly and carry a poor prognosis. Severe coronary artery disease, frequent comorbidity, late diagnosis, and treatments themselves are responsible for high morbidity and mortality rates. Reluctance to treat elderly patients with new mechanical or chemical revascularization techniques is due to the higher risk profile. ACS may or may not be accompanied by ST elevation: STEMI corresponds to acute myocardial infarction before myocardial necrosis, while non STEMI corresponds to unstable angina and subendocardial necrosis. Despite the high incidence of STEMI in the elderly, older patients have been excluded from large randomized trials. Chemical and mechanical reperfusion are the two recommended treatments for patients hospitalized before the 6th hour. Intravenous thrombolysis is the most common strategy: it offers a 26% reduction in mortality compared to conventional treatment, but carries a higher risk of brain hemorrhage than in younger patients. In high-throughput centers with experienced cardiologists, primary angioplasty seems to be the optimal strategy, with fewer deaths and recurrent ischemia. Two approaches are possible for NST-ACS: conservative or interventional. The latter includes medical treatment, early coronarography and revascularization by angioplasty or surgery. This strategy, combined with aspirin, clopidogrel, and glycoprotein II B/IIIa receptor inhibitors, offers a larger absolute reduction in the 30-day major adverse clinical event rate than conservative management. Dedicated randomized trials are needed to provide a more thorough picture of ACS management in the elderly.
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PMID:[Coronary syndromes in the elderly]. 1719 8

Osteopontin (OPN) is an adhesive glycoprotein linked to a variety of pathophysiological processes, with neuroprotective properties in ischemic injury. We examined the postischemic expression and localization of OPN in the rat brain after transient forebrain ischemia. The semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that OPN expression in the hippocampal CA1 region was biphasic, peaking at day 3 after reperfusion and again between days 14 and 28. The two phases of OPN induction occurred in a time- and cell-dependent manner in the ischemic hippocampus. OPN mRNA expression in activated microglia was first induced 1 day after reperfusion, reached a peak at 3 days, and returned to basal levels by 7 days. In contrast, OPN expression in reactive astrocytes was first induced by 10 days after reperfusion in the hippocampal CA1. Astroglial OPN expression further increased, reaching a peak at day 14 and was maintained up to day 28, the latest time point we examined. OPN immunoreactivity in the ischemic hippocampus matched the mRNA induction patterns. OPN protein was first localized in the astroglial cytoplasm and later in the extracellular matrix of the hippocampal CA1. The temporal and cellular patterns of OPN induction in the ischemic hippocampus suggest a multifunctional capacity in the pathogenesis of ischemic injury, with the increased OPN production and secretion by reactive astrocytes being involved in subsequent tissue repair and reorganization.
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PMID:Transient microglial and prolonged astroglial upregulation of osteopontin following transient forebrain ischemia in rats. 1739 66

To evaluate the safety and efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein llb/llla receptor, in the treatment of unstable angina and myocardial infarction without persistent ST elevation (acute coronary syndrome, ACS), a total of 200 patients were randomly assigned to a heparin group and a tirofiban+heparin group on double-blind basis and the treatment effects of the two protocols on ACS were compared when the patients of both groups were taking aspirin at the same time. The composite primary end-point events consisted of death, myocardial infarction, or refractory ischemia. Our results showed that the frequency of the composite primary end point events in 30 days was lower in tirofiban+heparin group as compared with that of heparin group (13.9% vs 29.3 %, P=0.010). The rates of the other composite end point events in the tirofiban+heparin group were also lower than those in the heparin group in 4.5 days and in 30 days. Bleeding complication occurred in 7.0% of the patients receiving heparin alone and in 12.7% of the patients receiving tirofiban and heparin in combination (P=0.1717). The study showed that the incidence of ischemic events in patients with ACS receiving tirofiban+heparin was lower when compared with that of patients who received only heparin and aspirin, suggesting that tirofiban might be of special value in the treatment of ACS.
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PMID:Evaluation on the safety and efficacy of tirofiban in the treatment of acute coronary syndrome. 1749 80

Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization; however, only a small proportion of injected cells home to the lesion and incorporate into the neocapillaries. Consequently, this type of cell therapy requires substantial improvement to be of clinical value. Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors and their ephrin ligands are key regulators of vascular development. We postulated that activation of the EphB4/ephrin-B2 system may enhance EPC proangiogenic potential. In this report, we demonstrate in a nude mouse model of hind limb ischemia that EphB4 activation with an ephrin-B2-Fc chimeric protein increases the angiogenic potential of human EPCs. This effect was abolished by EphB4 siRNA, confirming that it is mediated by EphB4. EphB4 activation enhanced P selectin glycoprotein ligand-1 (PSGL-1) expression and EPC adhesion. Inhibition of PSGL-1 by siRNA reversed the proangiogenic and adhesive effects of EphB4 activation. Moreover, neutralizing antibodies to E selectin and P selectin blocked ephrin-B2-Fc-stimulated EPC adhesion properties. Thus, activation of EphB4 enhances EPC proangiogenic capacity through induction of PSGL-1 expression and adhesion to E selectin and P selectin. Therefore, activation of EphB4 is an innovative and potentially valuable therapeutic strategy for improving the recruitment of EPCs to sites of neovascularization and thereby the efficiency of cell-based proangiogenic therapy.
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PMID:PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells. 1751 Jul 5

Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information.Moreover, in the failing human heart, multiple components of the IL-6- glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection. This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.
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PMID:Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis. 1791 16

Peripheral artery disease (PAD) is mostly related to atherosclerosis. Autoimmunity and, in particular, antibodies to cardiolipin (aCL) and phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) might influence the development of atheroma. Beta2-glycoprotein I (beta2-gpI) has been found in atheroma. It has previously been shown that immunoglobulin A (IgA) anti-beta2-gpI antibodies are associated with a risk of cerebral ischemia and myocardial infarction. This case control study aimed to determine whether elevated levels of aCL/anti-beta2-gpI antibodies are associated with a risk of symptomatic PAD (sPAD). Cases comprised a nonselected population of patients with sPAD (intermittent claudication or critical ischemia). Patient recruitment was based on arteriography changes. Controls were selected from patients admitted to orthopedic wards as a result of fractures or muscle-ligamentous disorders. Age, sex, race, hypertension, smoking, diabetes mellitus, and hypercholesterolemia were evaluated as risk factors in both groups. IgG/IgM/IgA aCL and anti-beta2-gpI were detected by enzyme-linked immunoabsorbant assays (ELISA). To estimate the grade of association of antibodies with sPAD, odds ratios (OR) were calculated. Logistic regression was utilized for adjustment of confounding factors. Seventy-seven cases and 93 controls were studied. The mean age was 61.5 years for cases and 47.5 years for controls (p <0.001). Among the risk factors evaluated, the presence of hypertension showed the strongest association with sPAD (OR 12.1; 95%CI 5.8-30). The presence of IgA anti-beta2-gpI was independently associated with sPAD (OR 5.4; 95%CI 1.8-15.8; p = 0.01). IgA aCL was strongly associated with the outcome (nonadjusted OR 11.5 after Agresti correction). IgA aCL and IgA anti-beta2-gpI antibodies were not associated with any known risk factors for sPAD or with arteriography changes. The occurrence of these autoantibodies might represent one of the links between autoimmunity and atherosclerosis in patients with sPAD.
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PMID:Autoantibodies to the atheroma component beta2-glycoprotein I and risk of symptomatic peripheral artery disease. 1762 83

Interleukin (IL)-6 family cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, play important roles in the maintenance of cardiac homeostasis. IL-11, a member of IL-6 family cytokines, is expressed in cardiac myocytes, though it remains to be elucidated how IL-11 functions in the hearts. In the present study, first, we showed that IL-11 administration reduced the ischemia/reperfusion injury in the hearts. IL-11 receptor alpha was expressed in cardiomyocytes. IL-11 treatment rapidly activated signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) 1/2 in cardiac myocytes. IL-11 stimulation resulted in the translocation of phosphorylated STAT3 into nuclei. Immunofluorescence microscopic analyses revealed that IL-11 treatment led to the cell elongation, as is the case with other cardiotrophic members of IL-6 family, such as leukemia inhibitory factor. Finally we showed that IL-11 treatment conferred the resistance to cell death induced by hydrogen peroxide, which was abrogated by adenoviral transfer of dominant negative STAT3, but not by the inhibition of ERK1/2 with U0126. These findings indicate that IL-11 mediates cytoprotective signals in cardiomyocytes, proposing that IL-11 has the potential to exhibit cardioprotection as a novel biological function.
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PMID:Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine. 1762 6

Erythropoietin (EPO) is a 30,400 daltons glycoprotein, consisting of 165 amino acids produced mainly in the kidney and in the liver and regulating erythrocyitosis. It primarily acts on erythroid precursor cell at colony-forming units-erythroid stage inhibiting the apoptosis. EPO binds on a specific membrane receptor thereby activating at least three specific intracellular signaling pathways, such as phosphatidylinositol 3-kinase/ protein kinase B, Ras-mitogen-activated protein kinase and some members of the signal transducers and activators of transcription family. In addition to kidney and liver, EPO mRNA has been detected in other tissues; accordingly EPO receptor has been identified in several type of cells and recent reports have suggested new roles for EPO in non-haematopoietic tissues with a robust evidence for neuroprotective and cardioprotective activity. In different animal models, in vitro, in isolated perfused heart and in vivo, recombinant human erythropoietin protects heart from ischemia reperfusion injury and reduces myocardial damage. EPO tissue protective activity can be separated from erythropoietic activity. Molecules owing the first property but not the second one have been described. In patients with acute myocardial infarction serum EPO level correlates inversely with infarct size. Acute coronary syndrome, extracorporeal circulation and percutaneous coronary intervention are potential fields of application for tissue protective EPO activity to reduce myocardial damage, increase cardiac function ad improve outcome.
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PMID:Structure, production and function of erythropoietin: implications for therapeutical use in cardiovascular disease. 1789 76

Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information. Moreover, in the failing human heart, multiple components of the IL-6- glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology. Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection. This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.
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PMID:Survival pathways in hypertrophy and heart failure: the gp130-STAT axis. 1753 Mar 15


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