Pretreatment of Human Cerebrovascular Endothelial Cells with <scp>CO</scp>‐releasing Molecule‐3 Interferes with <scp>JNK</scp>/<scp>AP</scp>‐1 Signaling and Suppresses <scp>LPS</scp>‐induced Proadhesive Phenotype

Serizawa, Fukashi; Patterson, Eric K.; Potter, Richard F.; Fraser, Douglas D.; Cepinskas, Gediminas

doi:10.1111/micc.12161

Cited by 19 publications

(16 citation statements)

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“…These results support our recent findings demonstrating significant accumulation of leukocytes in the microcirculation of the skeletal muscle of CS animals . The potency of CS serum in the induction of PMN adhesion to endothelial cells in vitro was greater in comparison with that observed in sepsis‐relevant stimulus (lipopolysaccharide (LPS)‐challenged human cerebrovascular endothelial cells) or endothelial cells stimulated with plasma of diabetic ketoacidosis patients …”

Section: Discussionsupporting

confidence: 90%

“…CORM‐3‐dependent inhibition of E‐selectin and VCAM‐1 expression in TNF‐α‐stimulated HUVECs has also been demonstrated . On the other hand, and contrary to the above, CORM‐3 failed to suppress ICAM‐1 and E‐selectin expression in TNF‐α‐stimulated HUVECs or LPS‐stimulated human cerebrovascular endothelial cells, while showing high effectiveness in reducing expression of VCAM‐1 . Finally, it has been found that CORM‐3 suppressed PMN‐HUVEC adhesive interaction by reducing CD11b (α M β 2 ‐integrin) surface levels in platelet‐activating factor (PAF)‐stimulated PMN …”

Section: Discussionmentioning

confidence: 79%

“…ing high effectiveness in reducing expression of VCAM-1. 50 Finally, it has been found that CORM-3 suppressed PMN-HUVEC adhesive interaction by reducing CD11b (α M β 2 -integrin) surface levels in platelet-activating factor (PAF)-stimulated PMN. 53 Following firm leukocyte adhesion to the vascular endothelium, Despite the demonstrated protective effects of CORM-3 (as well as other CO donors), several aspects still need to be considered for its future clinical applicability.…”

Section: Lps-stimulated Human Cerebrovascular Endothelial Cells Whilmentioning

confidence: 99%

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Carbon monoxide‐releasing molecule‐3 (CORM‐3) offers protection in an in vitro model of compartment syndrome

et al. 2019

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Objective Limb compartment syndrome (CS), a complication of trauma, results in muscle necrosis and cell death; ischemia and inflammation contribute to microvascular dysfunction and parenchymal injury. Carbon monoxide‐releasing molecule‐3 (CORM‐3) has been shown to protect microvascular perfusion and reduce inflammation in animal models of CS. The purpose of the study was to test the effect of CORM‐3 in human in vitro CS model, allowing exploration of the mechanism(s) of CO protection and potential development of pharmacologic treatment. Methods Confluent human vascular endothelial cells (HUVECs) were stimulated for 6 h with serum isolated from patients with CS. Intracellular oxidative stress (production of reactive oxygen species (ROS)) apoptosis, transendothelial resistance (TEER), polymorphonuclear leukocyte (PMN) activation and transmigration across the monolayer in response to the CS stimulus were assessed. All experiments were performed in the presence of CORM‐3 (100 μM) or its inactive form, iCORM‐3. Results CS serum induced a significant increase in ROS, apoptosis and endothelial monolayer breakdown; it also increased PMN superoxide production, leukocyte rolling and adhesion/transmigration. CORM‐3 completely prevented CS‐induced ROS production, apoptosis, PMN adhesion, rolling and transmigration, while improving monolayer integrity. Conclusion CORM‐3 offers potent anti‐oxidant and anti‐inflammatory effects, and may have a potential application to patients at risk of developing CS.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 79%

Section: Lps-stimulated Human Cerebrovascular Endothelial Cells Whilmentioning

confidence: 99%

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Carbon monoxide‐releasing molecule‐3 (CORM‐3) offers protection in an in vitro model of compartment syndrome

et al. 2019

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“…It is known that caspase-1 is responsible for generation of the active forms of IL-1β from pro-IL-1β. Thus lipopolysaccharide (LPS, 1β g/ml [35]) was used to induce pro-IL-1β. Though high glucose alone did not induce IL-1β expression, it was found that IL-1β was increased in high glucose and LPS treated EPCs compared with the LPS treated one.…”

Section: Resultsmentioning

confidence: 99%

PPARα Agonist Stimulated Angiogenesis by Improving Endothelial Precursor Cell Function Via a NLRP3 Inflammasome Pathway

Deng¹,

Han²,

Zheng³

et al. 2017

Cell Physiol Biochem

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Background: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators–activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice. Methods: Male C57BL/6 mice were randomly divided into three groups: control, STZ-induced diabetic mice and fenofibrate treated diabetic group. Wound closure was assessed by wound area and CD31 positive capillaries. Both the migration and tube formation capacities of EPCs were measured. Intracellular nitric oxide (NO) and superoxide (O₂^-) levels were determined. Activity of NLRP3 inflammasome in EPCs was assessed by measuring thioredoxin-interacting protein (TXNIP), NLRP3, and caspase-1 expression. Results: Compared with the untreated diabetic mice, wound closure and capillary densities were significantly increased in fenofibrate treated group. Fenofibrate treatment restored EPC function, increased NO production, and decreased O₂^- level in EPCs of diabetic mice. Furthermore, fenofibrate deregulated the activity of NLRP3 inflammasome by reducing TXNIP, NLRP3 and caspase-1 expression in EPCs of diabetic mice. In vitro, fenofibrate prevented high glucose induced EPC dysfunction, deregulated NLRP3 inflammasome activity. In addition, fenofibrate inhibited IL-1β expression caused by combination use of high glucose and lipopolysaccharide. Conclusion: Fenofibrate can accelerate wound healing in diabetic mice, which at least in part was mediated by improving the impaired EPC function via a NLRP3 inflammasome pathway, suggesting the significance of PPARα agonists in the treatment of diabetes.

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“…The metabolic activity of HO-1 that provides CO, biliverdin and bilirubin would then amplify these protective and anti-inflammatory functions in multiple ways. For example, HO-1 induction, biliverdin/bilirubin and CO have been shown to inhibit the expression of adhesion molecules in the endothelium 88;113-117 and reduce leukocyte rolling and adhesion as early control of inflammation. In addition, CO liberated by CORM-3 inhibits myeloperoxidase activity, which produces in leukocytes strong oxidizing compounds like hypochlorous acid which cause endothelial oxidative stress and dysfunction.…”

Section: Ho-1 and Cardiovascular Protectionmentioning

confidence: 99%

Heme Oxygenase-1 and Carbon Monoxide in the Heart

Otterbein

Foresti

Motterlini

2016

Circulation Research

170

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Understanding the processes governing the ability of the heart to repair and regenerate after injury is crucial for developing translational medical solutions. New avenues of exploration include cardiac cell therapy and cellular reprogramming targeting cell death and regeneration. An attractive possibility is the exploitation of cytoprotective genes that exist solely for self-preservation processes and serve to promote and support cell survival. While the antioxidant and heat shock proteins are included in this category, one enzyme that has received a great deal of attention as a master protective sentinel is heme oxygenase-1 (HO-1), the rate-limiting step in the catabolism of heme into the bioactive signaling molecules carbon monoxide, biliverdin and iron. The remarkable cardioprotective effects ascribed to HO-1 are best evidenced by its ability to regulate inflammatory processes, cellular signaling and mitochondrial function ultimately mitigating myocardial tissue injury and the progression of vascular-proliferative disease. We discuss here new insights into the role of HO-1 and heme on cardiovascular health, and importantly, how they might be leveraged to promote heart repair after injury.

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Pretreatment of Human Cerebrovascular Endothelial Cells with CO‐releasing Molecule‐3 Interferes with JNK/AP‐1 Signaling and Suppresses LPS‐induced Proadhesive Phenotype

Cited by 19 publications

References 65 publications

Carbon monoxide‐releasing molecule‐3 (CORM‐3) offers protection in an in vitro model of compartment syndrome

Carbon monoxide‐releasing molecule‐3 (CORM‐3) offers protection in an in vitro model of compartment syndrome

PPARα Agonist Stimulated Angiogenesis by Improving Endothelial Precursor Cell Function Via a NLRP3 Inflammasome Pathway

Heme Oxygenase-1 and Carbon Monoxide in the Heart

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