Ischemia-Induced Up-Regulation of Heme Oxygenase-1 Protects From Apoptotic Cell Death and Tissue Necrosis

Harder, Yves; Amon, M.; Schramm, René; Rücker, Martin; Scheuer, Cláudia; Pittet, Brigitte; Erni, Dominique; Menger, Michael D.

doi:10.1016/j.jss.2007.12.773

Cited by 15 publications

(14 citation statements)

References 46 publications

(58 reference statements)

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“…Interestingly, HO‐1 expression in group II was significantly higher than that in group I. This may be due to the protective mechanism that counteracts the ischemic insult, which has been demonstrated in a previous study …”

Section: Discussionsupporting

confidence: 53%

“…First, in the cell therapy group, HO‐1 expression increased significantly. HO‐1 is an enzyme that disassembles heme into ferrous iron, biliverdin, and carbon monoxide (CO); biliverdin from heme could be a free radical scavenger, and CO has a potent vasodilatory function . For this reason, increase of HO‐1 in the cell therapy group may have enhanced skin flap survival in our study.…”

Section: Discussionmentioning

confidence: 81%

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Improved skin flap survival in venous ischemia‐reperfusion injury with the use of adipose‐derived stem cells

et al. 2015

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 81%

Improved skin flap survival in venous ischemia‐reperfusion injury with the use of adipose‐derived stem cells

et al. 2015

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“…Among the three mammalian isoforms of HO, only the HO-1 is inducible. Activation of HO-1 has been shown to minimize the damage after ischemia followed by reperfusion in a number of organ systems including the skin flap tissues [6,18,34,35]. VEGF is one of the most important growth factors involved in vasculogenesis and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Angiogenesis is an important factor for the survival of random-pattern skin flap [4]. HIF-1α is known to regulate angiogenesis and microcirculation through mediators, such as vascular endothelial growth factor (VEGF) [5] and heme oxygenase (HO)-1 [6]. Thus, indicating the role of HIF-1α expression in the survival of random-pattern skin flaps.…”

Section: Introductionmentioning

confidence: 99%

Isoflurane Preconditioning Increases Survival of Rat Skin Random-Pattern Flaps by Induction of HIF-1a Expression

Sun

Zhang

et al. 2013

Cell Physiol Biochem

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Background: Survival of random-pattern skin flaps is important for the success of plastic and reconstructive surgeries. This study investigates isoflurane-induced protection against ischemia of skin flap and the underlying molecular mechanism in this process. Methods: Human umbilical vein endothelial cells (HUVECs) and human skin fibroblast cells were exposed to isoflurane for 4 h. Expression of hypoxia inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) were analyzed up to 24 h post isoflurane exposure using qRT-PCR and western blot, or ELISA analyses. PI3K inhibitors - LY 294002 and wortmannin, mTOR inhibitor - rapamycin, and GSK3β inhibitor - SB 216763 were used respectively to assess the effects of isoflurane treatment and HIF-1α expression. Furthermore, 40 rats were randomly divided into 5 groups (control, isoflurane, scrambled siRNA plus isoflurane, HIF-1α siRNA plus isoflurane, and DMOG) and subjected to random-pattern skin flaps operation. Rats were prepared for evaluation of flap survival and full-feld laser perfusion imager (FLPI) (at 7 day) and microvessel density evaluation (at 10 day). Results: Isoflurane exposure induced expression of HIF-1α protein, HO-1 and VEGF mRNA and proteins in a time-dependent manner. Both LY 294002 and wortmannin inhibited phospho-Akt, phospho-mTOR, phospho-GSK 3β and HIF-1α expression after isoflurane exposure. Both wortmannin and rapamycin inhibited isoflurane-induced phospho-4E-BP1 (Ser 65) and phospho-P70^s6k (Thr 389) and HIF-1α expression. SB 216763 pre-treatment could further enhance isoflurane-induced expression of phospho-GSK 3β (Ser 9) and HIF-1α protein compared to the isoflurane-alone cells. In animal experiments, isoflurane alone, scrambled siRNA plus isoflurane, or DMOG groups had significantly upregulated vascularity and increased survival of the skin flaps compared to the controls. However, HIF-1α knockdown abrogated the protective effect of isoflurane preconditioning in rats. Conclusions: Isoflurane preconditioning improves survival of skin flaps by up the regulation of HIF-1α expression via Akt-mTOR and Akt-GSK 3β signaling pathways.

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“…In all of these studies, flaps are designed to demonstrate maximum necrosis in the control group with endpoints of improved flap survival over the control group. Multiple studies demonstrate necrosis in the control group [4][5][6][7][8] . This stands in opposition to the primary goal of clinical flap design, which is to ensure 100% flap survival without necrosis.…”

Section: Introductionmentioning

confidence: 99%

Novel Irradiated Axial Rotational Flap Model in the Rodent

Luginbuhl

Modest

Yan

et al. 2013

JAMA Facial Plast Surg

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Part of the Otolaryngology Commons This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in

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Ischemia-Induced Up-Regulation of Heme Oxygenase-1 Protects From Apoptotic Cell Death and Tissue Necrosis

Cited by 15 publications

References 46 publications

Improved skin flap survival in venous ischemia‐reperfusion injury with the use of adipose‐derived stem cells

Improved skin flap survival in venous ischemia‐reperfusion injury with the use of adipose‐derived stem cells

Isoflurane Preconditioning Increases Survival of Rat Skin Random-Pattern Flaps by Induction of HIF-1a Expression

Novel Irradiated Axial Rotational Flap Model in the Rodent

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