UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day 1 (pre-treatment: aspirin = 3.1 +/- 0.5%, nitroaspirin = 3.9 +/- 0.7%, p = NS), and on day 28 (aspirin = 3.4 +/- 0.7%, NCX 4016 = 3.2 +/- 0.6%, p = NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = -1.15%, nitroaspirin = -1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirintreated group (-1.46%) while it was abolished in the NCX 4016-treated group (+0.79%, p = 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-1 which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.
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PMID:Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication. 1733 96

Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. The mechanism(s) by which acute and chronic myocardial ischemia translate into the characteristic features of ischemic cardiomyopathy is unresolved at present. We hypothesized that such translation relates to modification of specific gene expression programs during acute and chronic ischemic insults to the myocardium. Global mRNA expression profiles by Affymetrix HG_U133A GeneChip analysis on 33 samples was performed on non-failing human left ventricular myocardium during acute and chronic ischemia in 6 patients undergoing coronary artery by-pass grafting. Results were confirmed by real-time quantitative RT-PCR in 14 patients and supported by histology and immunohistochemistry analyses. Acute ischemia elicited an acute inflammatory response including IL-6, IL-8, MCP-1, VCAM-1 and CYR-61 with an attenuated increase of IL-6 and IL-8 in chronic ischemic myocardium compared to normal myocardium. High mRNA expression of connective tissue growth factor (CTGF) was present in chronic ischemic myocardium with a high degree of correlation between CTGF and mRNA expression of specific genes (e.g. thrombospondin 4, collagen type Ialpha2, versican, adlican, latent transforming growth factor beta binding protein 2 and fibronectin) involved in extracellular matrix remodelling. In conclusion, acute inflammatory induction (e.g. IL-8, IL-6, VCAM-1 and MCP-1) and an acute phase CCN family gene with effects on matrix interactions (CYR-61) might play important roles in the coupling between acute ischemic episodes and chronic myocardial remodelling. In addition, the findings support an important role of CTGF signalling in chronic extracellular matrix remodelling in chronic coronary artery disease.
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PMID:Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. 1734 75

In this study, we have investigated the role of the cannabinoid CB(2) (CB(2)) receptor in an in vivo mouse model of hepatic ischemia/reperfusion (I/R) injury. In addition, we have assessed the role of the CB(2) receptor in TNF-alpha-induced ICAM-1 and VCAM-1 expression in human liver sinusoidal endothelial cells (HLSECs) and in the adhesion of human neutrophils to HLSECs in vitro. The potent CB(2) receptor agonist HU-308, given prior to the induction of I/R, significantly attenuated the extent of liver damage (measured by serum alanine aminotransferase and lactate dehydrogenase) and decreased serum and tissue TNF-alpha, MIP-1alpha, and MIP-2 levels, tissue lipid peroxidation, neutrophil infiltration, DNA fragmentation, and caspase 3 activity. The protective effect of HU-308 against liver damage was also preserved when given right after the ischemic episode. HU-308 also attenuated the TNF-alpha-induced ICAM-1 and VCAM-1 expression in HLSECs, which expressed CB(2) receptors, and the adhesion of human neutrophils to HLSECs in vitro. These findings suggest that selective CB(2) receptor agonists may represent a novel, protective strategy against I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis.
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PMID:Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. 1765 47

Apolipoprotein A-I (apoA-I) mimetic peptides may represent an alternative to apoA-I for large-scale production of synthetic high-density lipoproteins (sHDL) as a therapeutic agent. In this study, the cardioprotective activity of sHDL made with either L37pA peptide or its d-stereoisomer, D37pA, was compared to sHDL made with apoA-I. The peptides were reconstituted with palmitoyl-oleoyl-phosphatidylcholine, which yielded sHDL particles comparable to apoA-I sHDL in diameter, molecular weight, and alpha-helical content. Pretreatment of endothelial cells with either peptide sHDL reduced tumor necrosis factor alpha-stimulated vascular cell adhesion molecule-1 expression to the same extent as apoA-I sHDL. In an isolated rat heart model of ischemia/reperfusion (I/R) injury, L37pA and D37pA sHDL significantly reduced postischemic cardiac contractile dysfunction compared to the saline control, as indicated by a 49.7 +/- 6.4% (L37pA; P < 0.001) and 53.0 +/- 9.1% (D37pA; P < 0.001) increase of left ventricular-developed pressure (LVDP) after reperfusion and by a 45.4 +/- 3.4% (L37pA; P < 0.001) and 49.6 +/- 2.6% (D37pA; P < 0.001) decrease of creatine kinase (CK) release. These effects were similar to the 51.3 +/- 3.0% (P < 0.001) increase of LVDP and 51.3 +/- 3.0 (P < 0.001) reduction of CK release induced by apoA-I sHDL. Consistent with their cardioprotective effects, all three types of sHDL particles mediated an approximate 20% (P < 0.001) reduction of cardiac tumor necrosis factor alpha (TNFalpha) content and stimulated an approximate 35% (P < 0.05) increase in postischemic release of prostacyclin. In summary, L37pA and D37pA peptides can form sHDL particles that retain a similar level of protective activity as apoA-I sHDL on the endothelium and the heart; thus, apoA-I mimetic peptides may be useful therapeutic agents for the prevention of cardiac I/R injury.
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PMID:Anti-inflammatory and cardioprotective activities of synthetic high-density lipoprotein containing apolipoprotein A-I mimetic peptides. 1804 29

Oxidative stress is important in several pathologies, including cardiovascular diseases such as atherosclerosis and cardiac ischemia-reperfusion injury. An important mechanism for adaptation to oxidative stress is induction of genes through the antioxidant response element (ARE), which regulates the expression of antioxidant and cytoprotective genes via the transcription factor Nrf2 (nuclear factor E2-related factor 2). As Nrf2-regulated genes are induced during oxidant stress occurring, for example, in reperfusion after ischemia, we took a novel approach to exploit ARE for the development of oxidative stress-inducible gene therapy vectors. To this end, one, two or three ARE-containing regions from human NAD(P)H:quinone oxidoreductase-1, glutamate-cysteine ligase modifier subunit and mouse heme oxygenase-1 were cloned into a vector expressing luciferase under a minimal SV40 promoter. The construct, which was the most responsive to ARE-inducing agents, was chosen for further studies in which a lentiviral vector was produced for an efficient transfer to endothelial cells. Heme oxygenase-1 (HO-1), which has well-characterized anti-inflammatory properties, was used as the therapeutic transgene. In human endothelial cells, ARE-driven HO-1 overexpression inhibited nuclear factor-kappaB activation and subsequent vascular cell adhesion molecule-1 expression induced by tumor necrosis factor-alpha. We conclude that the ARE element is a promising alternative for the development of oxidative stress-inducible gene therapy vectors.
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PMID:Oxidative stress-inducible lentiviral vectors for gene therapy. 1844 15

Ischaemia followed by reperfusion (I/R) can induce inflammation and injury and is a risk factor for delayed graft function and rejection of transplanted kidneys. Inflammation is regulated by NF-kappaB transcription factors which induce pro-inflammatory molecules in endothelial cells (EC). We examined whether A20, a negative regulator of NF-kappaB, can protect kidneys from I/R injury. To mimic the fluctuations in endothelial oxygenation that occur during I/R we exposed cultured human umbilical vein EC (HUVEC) to hypoxia (1% O(2) for 4 h) followed by re-oxygenation (21% O(2) for 1 h-24 h). We observed transient expression of pro-inflammatory molecules (E-selectin, VCAM-1 and IL-8) and sustained expression of A20 in HUVEC exposed to hypoxia/re-oxygenation. The effect of A20 on endothelial responses to hypoxia/re-oxygenation was assessed. We observed that pre-treatment of HUVEC with an adenovirus containing A20 (Ad-A20) suppressed activation of NF-kappaB and induction of pro-inflammatory molecules by hypoxia/re-oxygenation, whereas a control adenovirus had little or no effect. Thus the induction of A20 may form a negative feedback loop in pro-inflammatory signalling in cells exposed to hypoxia/re-oxygenation. To validate our cell culture experiments we examined the role of A20 in renal responses to I/R. We observed that A20 was induced in rat kidneys exposed to I/R. Moreover, pre-treatment of animals with Ad-A20 significantly reduced acute tubular necrosis, renal expression of VCAM-1 and NF-kappaB activation in response to I/R, whereas pre-treatment with control adenovirus did not. Our observations suggest that A20 maintains physiological homeostasis in kidneys exposed to I/R by protecting them from inflammation and injury.
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PMID:The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation. 1894 30

Nuclear factor-kappa B (NF-kappaB) comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory responses. The NF-kappaB signals are activated via the canonical and/or noncanonical pathways in response to diverse stimuli. The excessive action of NF-kappaB signal-transduction pathways frequently causes self-injurious phenomena such as allergic diseases, vascular disorders, and ischemia-reperfusion neuronal damage. In the inner ear, the role of NF-kappaB has not been clarified because the activated NF-kappaB signals potentially induce both cytoprotective and cytotoxic target genes after ototoxic stimulation. In the present study, we investigated the response of NF-kappaB in both the canonical and noncanonical pathways to acoustic overstimulation (117 dB/SPL/2 hr) and followed the change of inflammatory factors (inducible nitric oxide synthase [iNOS], intracellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) in the cochlear lateral wall (CLW) and the rest of cochlea (RoC). By means of immunohistochemistry combined with confocal microscopy and reverse transcriptase-polymerase chain reaction techniques, we found the response of NF-kappaB family members (NF-kappa B1, 2, RelA, and RelB) at the transcription level. After the NF-kappaB signaling, the inflammatory factors were significantly increased in the CLW and the RoC. Additionally, at the protein level, the prominent expression of adhesion molecules (ICAM-1 and VCAM-1) was observed in the tissue around the capillaries in the stria vascularis. These results show that acoustic overstimulation causes the NF-kappaB signaling to overexpress the inflammatory factors in the inner ear, and the up-regulation of the adhesion molecules (ICAM-1 and VCAM-1) and iNOS potentially influence the hemodynamics and the cellular integrity in the stria vascularis.
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PMID:The influence of NF-kappaB signal-transduction pathways on the murine inner ear by acoustic overstimulation. 1918 19

The impairment of organ function due to ischemia-reperfusion injury is still an important problem in solid organ transplantation. Numerous experimental and clinical studies of native organs have shown that ischemia-reperfusion constitutes an acute inflammatory process involving cell surface adhesion molecule expression. These markers are crucial for the recruitment and infiltration of effector cells into the postischemic tissue. Purines released by the postischemic tissue as the products of the degradation of high-energy nucleotides can be regarded as markers of disturbed energy metabolism. The aim of this study was to examine the correlation between circulating adhesion molecules and purine metabolites in graft renal vein plasma during 49 cases of kidney reperfusion. E-selectin, ICAM-1, and VCAM-1 concentrations correlated positively with hypoxanthine concentrations during reperfusion, whereas the concentrations of ICAM-1 correlated negatively with xanthine concentrations. The results of the present study suggested that the concentrations of adhesion molecules in the renal vein during reperfusion correlated with purine metabolites, reflecting metabolic changes in renal tissue.
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PMID:Circulating adhesion molecules and purine nucleotides during kidney allograft reperfusion. 1924 70

Brain ischemia can usually disrupt the blood-brain barrier (BBB), increasing the permeability of BBB. Ischemic preconditioning could not only reduce neurons damage, but also protect the functions of BBB during brain ischemia. In this study, we used BBB model in vitro to examine the effects of preconditioning on cell viability, BBB permeability, tight junction and cell adhesion of rat brain microvascular endothelial cells (BMECs). The rat BMECs were exposed to 2.5 h of oxygen glucose deprivation (OGD) following 3 h of reoxygenation to simulate ischemia/reperfusion in vivo, using 0.5 h OGD as preconditioning. Results showed that OGD/reoxygenation induced cell death, increased BBB permeability, changed the distribution of endothelial cells tight junction protein ZO-1 and cellular framework protein F-actin, and increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). OGD preconditioning could partially protect cell viability and BBB permeability, maintain the membrane location of ZO-1 and F-actin, and decrease the expression of ICAM-1 and VCAM-1. Our study suggests that OGD preconditioning could stabilize the tight junction protein and alleviate cell adhesion to protect BBB function during ischemic stress.
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PMID:Effects of preconditioning on tight junction and cell adhesion of cerebral endothelial cells. 1933 28

The reperfusion of blood flow occurred in a number of conditions such as stroke and organ transplantation immensely augments tissue injury and causes more severe damage than prolonged ischemia. In the present study, we designed a novel double-layer parallel-plate flow chamber (PPFC) to develop an in vitro ischemia/reperfusion (I/R) injury model and examined the effects of I/R on inflammatory responses in human microvascular endothelial cells (HMEC-1). The expression of pro-inflammatory mediators, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in HMEC-1 was measured by quantitative real-time RT-PCR. The cells were also pre-treated with antioxidant pyrrolidine dithiocarbamate (PDTC) to verify involvement of an oxidative mechanism in I/R injury in vitro. The morphological changes and attenuated expression of pro-inflammatory mediators were observed in HMCE-1 exposed to the physiological flow. In contrast, I/R markedly and significantly up-regulated expression of pro-inflammatory mediators in HMEC-1. Additionally, pretreatment with PDTC significantly reduced I/R-mediated overexpression of pro-inflammatory mediators. The data from the present study provide evidence demonstrating that our newly designed PPFC can be utilized as an effective in vitro cell culture model system to develop new drugs specifically targeting against ischemia/reperfusion (I/R) injury.
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PMID:A novel in vitro ischemia/reperfusion injury model. 1938 87

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