The role of endogenous heme oxygenase in the initiation of liver injury following limb ischemia/reperfusion

Nie, Robert G.; McCarter, Sarah D.; Harris, Kenneth A.; Lee, Patricia; Zhang, Xuchen; Bihari, Aurelia; Gray, Daryl; Wunder, Christian; Brock, Robert W.; Potter, Richard F.

doi:10.1016/s0168-8278(02)00025-9

Cited by 21 publications

(14 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using intravital video microscopy, we showed that induction of heme oxygenase (HO-1), the rate-limiting enzyme in the catabolism of heme into carbon monoxide (CO), biliverdin, and free iron (7), prevented hepatocellular death, microvascular perfusion deficits, and inflammation that results following hind limb ischemia/reperfusion (I/R) (8)(9)(10)(11)(12). It is now generally accepted that increased HO activity is protective in several models of hepatic stress.…”

mentioning

confidence: 99%

Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion

Ott¹,

Scott

Bihari

et al. 2004

FASEB j.

Self Cite

View full text Add to dashboard Cite

The induction of heme oxygenase (HO), the rate limiting enzyme in the conversion of heme into carbon monoxide (CO) and biliverdin, limits liver injury following remote trauma such as hind limb ischemia/reperfusion (I/R). Using intravital video microscopy, we tested the hypothesis that inhaled CO (250 ppm) would mimic HO-derived liver protection. Hind limb I/R significantly decreased sinusoidal diameter and volumetric flow, increased leukocyte accumulation within sinusoids, increased leukocyte rolling and adhesion within postsinusoidal venules, and significantly increased hepatocyte injury compared with naive animals. Inhalation of CO alone did not alter any microcirculatory or inflammatory parameters. Inhalation of CO following I/R restored volumetric flow, decreased stationary leukocytes within sinusoids, decreased leukocyte rolling and adhesion within postsinusoidal venules, and significantly reduced hepatocellular injury following hind limb I/R. HO inhibition did not alter microcirculatory parameters in naive mice, but did increase inflammation, as well as increase hepatocyte injury following hind limb I/R. Inhalation of CO during HO inhibition significantly reduced such microcirculatory deficits, hepatic inflammation, and injury in response to hind limb I/R. In conclusion, these results suggest that HO-derived hepatic protection is mediated by CO, and inhalation of low concentrations of CO may represent a novel therapeutic approach to prevent remote organ injury during systemic inflammatory response syndrome, or SIRS.

show abstract

mentioning

confidence: 99%

Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion

Ott¹,

Scott

Bihari

et al. 2004

FASEB j.

Self Cite

View full text Add to dashboard Cite

show abstract

“…They demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. They selected the HO-1 as a therapeutic target from among many other potential therapeutic genes, such as superoxide dismutase [50], nitric oxide synthase [51], and vascular endothelial growth factor [52] on the basis of its documented cytoprotective effects [53] for the purpose of demonstrating the feasibility and therapeutic potential of this strategy with a validated cardioprotective gene. However, they emphasize that this strategy can be extended to the expression of any gene or combination of gene(s) with therapeutic value for protection from ischemia-induced injury.…”

Section: Discussionmentioning

confidence: 99%

Comparison of continuous vs. pulsed focused ultrasound in treated muscle tissue as evaluated by magnetic resonance imaging, histological analysis, and microarray analysis

et al. 2008

View full text Add to dashboard Cite

The purpose of this study was to investigate the effect of different application modes of high intensity focused ultrasound (HIFU) to muscle tissue. HIFU was applied to muscle tissue of the flank in C3H/Km mice. Two dose regimes were investigated, a continuous HIFU and a short-pulsed HIFU mode. Three hours after HIFU treatment pre- and post-contrast T1-weighted, T2-weighted images and a diffusion-weighted STEAM sequence were obtained. After MR imaging, the animals were euthanized and the treated, and the non-treated tissue was taken out for histology and functional genomic analysis. T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the central parts throughout the tissue of both HIFU modes. A significantly higher diffusion coefficient was found in the muscle tissue treated with continuous wave focused ultrasound. Gene expression analysis revealed profound changes of 54 genes. For most of the analyzed genes higher expression was found after treatment with the short-pulse mode. The highest up-regulated genes encoded for the MHC class III (FC approximately 84), HSP 70 (FC approximately 75) and FBJ osteosarcoma related oncogene (FC approximately 21). Immunohistology and the immunoblot analysis confirmed the presence of HSP70 protein in both applied HIFU modes. The use of HIFU treatment on muscle tissue results in dramatic changes in gene expression; however, the same genes are up-regulated after the application of continuous or pulsed HIFU, indicating that the tissue reaction is independent of the type of tissue damage.

show abstract

“…In addition, given the widespread tropism of AAV (23) and its capability for long-term expression of therapeutic genes, the prevalence of hypoxia as a principal trigger of injury in diverse tissues, the ubiquitous distribution of hypoxia-inducible factor 1␣ (24,25), and the effectiveness of HO-1 in mediating tissue protection from I͞R injury, this approach is generally applicable to a variety of tissues that may undergo I͞R injury, such as the kidneys, lungs, liver, and brain. The selection of HO-1 as a therapeutic target from among many other potential therapeutic genes, such as superoxide dismutase (26), nitric oxide synthase (27,28), and vascular endothelial growth factor (29), was made on the basis of its documented cytoprotective effects (30,31) for the purpose of demonstrating the feasibility and therapeutic potential of this strategy with a validated cardioprotective gene. However, we emphasize that this strategy can be extended to the expression of any gene or combination of gene(s) with therapeutic value for protection from ischemia-induced injury.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Pachori

Melo

Hart

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia͞reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia͞reperfusion injury.

show abstract

The role of endogenous heme oxygenase in the initiation of liver injury following limb ischemia/reperfusion

Cited by 21 publications

References 20 publications

Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion

Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion

Comparison of continuous vs. pulsed focused ultrasound in treated muscle tissue as evaluated by magnetic resonance imaging, histological analysis, and microarray analysis

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

Contact Info

Product

Resources

About