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)

Neutrophil activation and tumor necrosis factor-alpha (TNF-alpha) induction play a critical role in ischemia-reperfusion-induced intestinal inflammation. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate reperfusion-induced intestinal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression. Intestinal damage was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 30 min followed by reperfusion. Reperfusion after 30 min ischemia resulted in an increase in luminal protein concentrations with levels reaching a maximum after 60 min of reperfusion. In contrast, pretreatment with pioglitazone 2 h before ischemia inhibited the increase in luminal protein concentrations after 60 min reperfusion in a dose-dependent manner (1-30 mg/kg). The increase in tissue-associated myeloperoxidase activity, an index of neutrophil infiltration, after reperfusion was significantly inhibited by pretreatment with pioglitazone. Pioglitazone also inhibited increases in intestinal TNF-alpha protein and mRNA expression determined by ELISA and RT-PCR, respectively. In conclusion, activation of PPAR-gamma may represent a novel approach to the treatment of intestinal inflammation induced by ischemia-reperfusion.
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PMID:Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, in rats. 1268 13

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. The aim of the present study was to investigate the effects of pioglitazone on ischemia-reperfusion (I/R)-induced gastric mucosal injury in rats. Gastric ischemia was induced for 30 min by applying a small vascular clamp to the celiac artery and reperfusion was produced by removal of the clamp in male Sprague-Dawley rats treated with and without pioglitazone. Pioglitazone was given to the rats intraperitoneally 2 h before the vascular clamping. The area of gastric mucosal erosion (erosion index) significantly increased from mean basal levels after 60 min of reperfusion. This erosion index was significantly inhibited by pretreatment with pioglitazone in a dose-dependent manner. The concentration of thiobarbituric acid reactive substances (TBARS) and myeloperoxidase (MPO) activity in the gastric mucosa were both significantly increased after I/R, and pretreatment with pioglitazone significantly reduced these increases. The contents of both mucosal TNF-alpha and CINC-2beta in the I/R group were significantly increased compared with the levels in the sham-operated group. These increases in TNF-alpha and CINC-2beta were significantly inhibited by pretreatment with pioglitazone at a dose of 10 mg/kg. The results of the present study indicate that pioglitazone inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats. This investigation suggests that pioglitazone has potential as a new therapeutic agent for reperfusion injury.
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PMID:A specific peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, pioglitazone, ameliorates gastric mucosal damage induced by ischemia and reperfusion in rats. 1268 26

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors which regulate the expression of target genes. Three types of PPAR have been identified: PPAR alpha, PPAR beta/delta and PPAR gamma. The known endogenous PPAR ligands are polyunsaturated fatty acids and eicosanoids, such as 15-deoxy-delta 12,14-prostaglandin J2 and leukotriene B4. Two classes of drugs, fibrates and thiazolidinediones, bind to PPAR alpha and PPAR gamma, respectively. PPARs are involved in the regulation of the lipid metabolism and adipogenesis but are also expressed in the vasculature. PPARs activators inhibit inflammatory reactions within the vascular wall, inhibit vascular smooth muscle cells migration and proliferation and affect foam cells formation by changing the expression of scavenger receptors. PPAR agonists lower blood pressure and improve endothelial function in different animal models of hypertension as well as in humans. PPAR gamma ligands inhibit the development of atherosclerosis in LDL receptor deficient and apolipoprotein E deficient mice and in diabetic humans. PPAR gamma agonists have also been shown to attenuate myocardial hypertrophy and protect against ischemia-reperfuion injury.
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PMID:[Peroxisome proliferator-activated receptors (PPAR) in pathophysiology of the circulatory system and prospective use of agonists of these receptors in therapy]. 1286 56

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a transcription factor that in some in vitro systems has been linked with downregulation of proinflammatory mediators, thus implicating a potential role for PPARalpha in the regulation of inflammatory processes. Hepatic ischemia-reperfusion injury is characterized by an intense acute inflammatory response that is dependent on a number of proinflammatory mediators. PPARalpha is abundantly expressed in hepatic parenchymal cells but not in Kupffer cells. This study examined whether PPARalpha is involved in regulation of the hepatic inflammatory response to ischemia-reperfusion. Mice nullizygous for PPARalpha had significantly greater liver injury than did their wild-type counterparts. Consistent with these findings, C57BL/6 mice treated with the PPARalpha agonist, WY-14643, had significantly less liver injury than mice receiving vehicle. PPARalpha-knockout mice also had greatly augmented liver neutrophil accumulation and modest increases in activation of the transcription factors NF-kappaB and activator protein-1. However, these effects were not associated with increased expression of proinflammatory cytokines or chemokines. In addition, PPARalpha-knockout mice expressed far less inducible nitric oxide synthase in liver than did wild-type mice after ischemia-reperfusion. Finally, treatment of cultured murine hepatocytes with WY-14643, a specific agonist of PPARalpha, protected cells against oxidant-induced injury. The data suggest that PPARalpha is an important regulator of the hepatic inflammatory response to ischemia-reperfusion in a manner that is independent of proinflammatory cytokines.
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PMID:Peroxisome proliferator-activated receptor-alpha regulates postischemic liver injury. 1461 82

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. PPAR-gamma has recently been implicated as a regulator of cellular proliferation and inflammatory responses. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce tissue injury associated with ischemia and reperfusion. The potential utility of PPAR-gamma ligands in ischemia and reperfusion will be discussed in this review.
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PMID:Peroxisome proliferator-activated receptors gamma ligands and ischemia and reperfusion injury. 1565 94

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR-gamma regulates gene expression by forming a heterodimer with the retinoid X receptor (RXR) before binding to sequence-specific PPAR response elements (PPREs) in the promoter region of target genes, thereby regulating several metabolic pathways, including lipid biosynthesis and glucose metabolism. Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic PPAR-gamma agonists, act as insulin sensitizers and are used in the treatment of type 2 diabetes. In the last few years, it has, however, become evident that the therapeutic effects of PPAR-gamma ligands reach far beyond their use as insulin sensitizers. Recently, PPAR-gamma has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR-gamma agonists may exert their anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes induced during macrophage differentiation and activation, by either PPAR-gamma-dependent or -independent mechanisms. Several lines of evidence suggest that TZDs protect the heart and other organs against the tissue injury caused by ischemia/reperfusion (I/R) injury and shock. This review discusses the anti-inflammatory signalling pathways activated by PPAR-gamma, as well as the potential therapeutic effects of PPAR-gamma agonists in animal models of ischemia/reperfusion, inflammation and shock.
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PMID:Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock. 1572 57

The pathogenesis of ischemia-reperfusion injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Peroxisome proliferator-activated receptor (PPAR)-gamma is considered an important immunomodulatory factor as well as a fatty acid regulator. In this study, we researched the expression of PPAR-gamma in renal ischemia-reperfusion injury of the rat. The right kidney was harvested and left renal artery and vein were clamped under laparotomy. The kidney was reperfused after 90 minutes of ischemia, and rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. PPAR-gamma expression was analyzed by immunohistochemical staining using monoclonal antibody. In normal kidney, PPAR-gamma staining was weak on endothelial cells, including mesangial cells. On the other hand, PPAR-gamma staining was weak on interstitial cells and strong on collecting ducts of medulla. From 1.5 to 5 hours after reperfusion, PPAR-gamma staining was strong on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. Twelve hours after reperfusion, PPAR-gamma staining was weak on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. PPAR-gamma is induced on collecting ducts, interstitial cells, and endothelial cells in a rat model having renal ischemia-reperfusion injury.
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PMID:Expression of peroxisome proliferator-activated receptor-gamma in renal ischemia-reperfusion injury. 1591 30

Thiazolidinediones, used for the treatment of diabetes mellitus type 2, modulate gene expression by binding to nuclear transcription factor, peroxisome proliferator-activated receptor-gamma. Peroxisome proliferator-activated receptor-gamma is expressed in several tissues, therefore, thiazolidinediones have biological effects on multiple organ systems. Here, we describe evidence that thiazolidinediones have beneficial effects on the cardiovascular system independent of their antidiabetic effect. Studies in animals have clearly shown that thiazolidinediones decrease blood pressure, left ventricular hypertrophy, development of atherosclerotic lesions, and protect myocardium from ischemia/reperfusion injury. Although relatively few studies in humans have been reported, the preponderance of available evidence suggests a beneficial effect of thiazolidinediones. Thus, by modulating gene expression, thiazolidinediones may provide a novel method for the prevention and treatment of cardiovascular diseases.
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PMID:Cardiovascular effects of the thiazolidinediones. 1618 18

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that regulate the expression of genes involved in a variety of biological processes, including lipid metabolism and insulin sensitivity. Members of the PPAR family-in particular, PPAR-gamma-have more recently been shown to broadly regulate inflammatory and reparative responses. PPAR-gamma is expressed in both alveolar macrophages and neutrophils, and the ligand-dependent activation of this receptor results in suppression of leukocyte effector responses, including cytokine production, the elaboration of reactive oxygen and nitrogen species, and migratory responses. In addition to antiinflammatory effects, PPAR-gamma regulates diverse processes in lung stromal/parenchymal cells, including cell growth, differentiation, and apoptosis. Studies examining in vivo effects of PPAR-gamma have produced complex and at times conflicting results. However, evidence to date generally suggests that PPAR-gamma functions to dampen inflammation and injury in various animal models of acute lung injury. PPAR-gamma may also play an important role in other inflammatory/immune lung diseases, including ischemia-reperfusion injury, allergic airway inflammation, and cancer. The role of PPAR-gamma in human lung diseases, including acute lung injury, requires further study.
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PMID:Peroxisome proliferator-activated receptor-{gamma} as a regulator of lung inflammation and repair. 1622 42

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, not only improves insulin resistance in patients with type II diabetes but also exerts a broad spectrum protective effects in variable animal models of neurologic or cardiovascular diseases. We studied the effect of rosiglitazone on angiogenesis and neurological recovery after focal cerebral ischemia. Rosiglitazone (3 mg/kg or 0.3 mg/kg, p.o.) was administered for 7 days prior to and 3 days after the induction of focal ischemia (total 10 days) in adult rats. The rosiglitazone-treated group showed the enhanced neurologic improvement, the reduced infarction volume compared to the ischemia-vehicle group with dose dependency, and the reduced hemispheric atrophy. Rosiglitazone treatment reduced TUNEL(+)/activated caspase-3(+) cells, MPO(+)/Ox-42(+) inflammatory cell infiltrations, caspase-3 activity, and Bax(+) cells, as compared to the ischemia-vehicle group. The vascular surface area, the vascular branch points, the vascular length, and the number of BrdU(+) endothelial cells were significantly increased in the rosiglitazone group compared with the ischemia-vehicle group. Rosiglitazone increased eNOS expression around the ischemic margin with downregulation of FasL. Here, we show that rosiglitazone treatment enhances angiogenesis and functional recovery with dose-dependent induction of ischemic tolerance.
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PMID:Peroxisome proliferator-activated receptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia. 1669 56


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