The importance of the effect of shear stress on endothelial cells in determining the performance of hemoglobin based oxygen carriers

Gaucher, Caroline; Paternotte, Estelle; Prin-Mathieu, Christine; Reeder, Brandon J.; Poitevin, Gael; Labrude, Pierre; Stoltz, Jean‐François; Cooper, Chris E.; Menu, Patrick

doi:10.1016/j.biomaterials.2008.09.051

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…Studies have documented induction of HO-1 as a cellular response to high oxidation states of Hb, as well as other proinflammatory responses. HO-1 transcription is markedly increased when Hb or HBOCs are added to endothelial cells (92). Extracellular addition of Hb and polymerized Hb to rats and guinea pigs caused HO-1 induction, as well as ferritin production (46).…”

Section: A the Rational Design Of Hemoglobin-based Oxygen Carriersmentioning

confidence: 99%

“…Noncovalently bound, oxidatively modified d-type chlorin hemes have been detected in humans under conditions of mild stress (278) and with HBOCs (Hb-Dex-BTC and Oxyglobin) added to endothelial cells (92). However, the highest percentages of damaged hemes detected were in stock preparations of HBOCs and decreased rapidly after shear stress to endothelial cells, suggesting that stress conditions facilitate the apparatus to repair or remove oxidatively modified heme groups (92). The reactivity between Hbs with oxidatively modified heme groups and HO-1 is not currently known.…”

Section: A the Rational Design Of Hemoglobin-based Oxygen Carriersmentioning

confidence: 99%

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The Redox Activity of Hemoglobins: From Physiologic Functions to Pathologic Mechanisms

Reeder

2010

Antioxidants & Redox Signaling

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Pentacoordinate respiratory hemoproteins such as hemoglobin and myoglobin have evolved to supply cells with oxygen. However, these respiratory heme proteins are also known to function as redox enzymes, reacting with compounds such as nitric oxide and peroxides. The recent discoveries of hexacoordinate hemoglobins in vertebrates and nonsymbiotic plants suggest that the redox activity of globins is inherent to the molecule. The uncontrolled formation of radical species resulting from such redox chemistry on respiratory hemoproteins can lead to oxidative damage and cellular toxicity. In this review, we examine the functions of various globins and the mechanisms by which these globins act as redox enzymes under physiologic conditions. Evidence that redox reactions also occur under disease conditions, leading to pathologic complications, also is examined, focusing on recent discoveries showing that the ferryl oxidation state of these hemoproteins is present in these disease states in vivo. In addition, we review the latest advances in the understanding of globin redox mechanisms and how they might affect cellular signaling pathways and how they might be controlled therapeutically or, in the case of hemoglobin-based blood substitutes, through rational design.

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Section: A the Rational Design Of Hemoglobin-based Oxygen Carriersmentioning

confidence: 99%

Section: A the Rational Design Of Hemoglobin-based Oxygen Carriersmentioning

confidence: 99%

The Redox Activity of Hemoglobins: From Physiologic Functions to Pathologic Mechanisms

Reeder

2010

Antioxidants & Redox Signaling

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166

184

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“…Scaling the process up to produce the quantities required to meet the anticipated demands were feared to exceed the costs that could be sustained in the eventual marketplace. Nevertheless, this recombinant technology remains an excellent approach for future research.Current HBOCs result in vasoconstriction, which is evident as a rapid rise in peripheral vascular resistance and blood pressure, commonly associated with bradycardia, decreased cardiac output, and reduced perfusion to vital organs (15,28,36). Vasoconstriction is currently perceived to be the critical barrier hampering HBOC development (1, 41).…”

mentioning

confidence: 98%

“…Current HBOCs result in vasoconstriction, which is evident as a rapid rise in peripheral vascular resistance and blood pressure, commonly associated with bradycardia, decreased cardiac output, and reduced perfusion to vital organs (15,28,36). Vasoconstriction is currently perceived to be the critical barrier hampering HBOC development (1,41).…”

mentioning

confidence: 99%

Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins

Cabrales

Zhou

Harris

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Hemoglobin (Hb)-based O(2) carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O(2) deficit under conditions of anemia and traumatic blood loss. The O(2) transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O(2) delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). After an initial moderate hemodilution to 18% hematocrit, animals were randomly assigned to exchange transfusion groups based on the type of PolybHb solution used (namely, T-state PolybHb and R-state PolybHb groups). Measurements of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O(2) levels were performed at 11% hematocrit. Both PolybHbs were infused at 10 g/dl, and their viscosities were higher than nondiluted blood. Restitution of the O(2) carrying capacity with T-state PolybHb exhibited lower arterial pressure and higher functional capillary density compared with R-state PolybHb. Central arterial O(2) tensions increased significantly for R-state PolybHb compared with T-state PolybHb; conversely, microvascular O(2) tensions were higher for T-state PolybHb compared with R-state PolybHb. The increased tissue Po(2) attained with T-state PolybHb results from the larger amount of O(2) released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O(2) affinity of R-state PolybHb prevented O(2) bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O(2) carrier, is a quintessential example of an appropriately engineered O(2) carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs.

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“…S-nitrosation can have antioxidant effects by inhibiting NADPH oxidase activity (Selemidis et al, 2007), or by promoting the ROS scavenging activity of thioredoxin-1 via S-nitrosation on Cys-69 residue (Haendeler et al, 2002;Liu et al, 2004a,b). Indeed, endothelial cells subjected to physiological shear stress produce NO (Gaucher et al, 2007;Gaucher-Di Stasio et al, 2009) and increase protein S-nitrosation independently of cGMP-dependent signaling (Hoffmann et al, 2003;Huang et al, 2009). In contrast, after TNF-α or mild oxidized LDL treatment endothelial cells present with decreased S-nitrosation (Hoffmann et al, 2001).…”

Section: Protein S-nitrosationmentioning

confidence: 99%

Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology

Belcastro

Gaucher

Corti

et al. 2017

Biological Chemistry

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Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the so-called 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins. The peculiar reactivity of these residues results in two major classes of modifications, with incorporation of NO moieties (S-nitrosation, leading to formation of protein S-nitrosothiols) or binding of low molecular weight thiols (S-thionylation, i.e . in particular S-glutathionylation, S-cysteinylglycinylation and S-cysteinylation).A wide array of proteins have been thus analyzed in detail as far as their susceptibility to either modification or both, and the resulting functional changes have been described in a number of experimental settings. The present review aims to provide an update of available knowledge in the field, with a special focus on the respective (sometimes competing and antagonistic) roles played by protein S-nitrosations and S-thionylations in biochemical and cellular processes specifically pertaining to pathogenesis of cardiovascular diseases.

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The importance of the effect of shear stress on endothelial cells in determining the performance of hemoglobin based oxygen carriers

Cited by 14 publications

References 31 publications

The Redox Activity of Hemoglobins: From Physiologic Functions to Pathologic Mechanisms

The Redox Activity of Hemoglobins: From Physiologic Functions to Pathologic Mechanisms

Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins

Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology

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