Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs

Zardi, Enrico Maria; Zardi, Domenico Maria; Cacciapaglia, Fabio; Dobrina, Aldo; Amoroso, Antonio; Picardi, Antonio; Afeltra, Antonella

doi:10.1016/j.intimp.2004.10.016

Cited by 41 publications

(21 citation statements)

References 240 publications

(252 reference statements)

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“…PGI 2 has been postulated to play a key role in regulating both innate and acquired immunity and the effects are, for the most part, immunosuppressive or antiinflammatory, resulting from IP-mediated increases in cAMP (reviewed in Ref. 27). Inhibitory effects on innate immunity include the suppression of adhesion molecule expression by endothelial cells and leukocytes (27), the reduction of reactive oxygen intermediate production by neutrophils (28), the impairment of inflammatory cytokine generation by pathogen-stimulated macrophages (29) and dendritic cells (R.S.…”

Section: Discussionmentioning

confidence: 99%

“…27). Inhibitory effects on innate immunity include the suppression of adhesion molecule expression by endothelial cells and leukocytes (27), the reduction of reactive oxygen intermediate production by neutrophils (28), the impairment of inflammatory cytokine generation by pathogen-stimulated macrophages (29) and dendritic cells (R.S. Peebles, unpublished observation), and the inhibition of NK-cell mediated cytotoxicity (30).…”

Section: Discussionmentioning

confidence: 99%

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Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Aronoff

Peres

Serezani

et al. 2007

The Journal of Immunology

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PGI2 (prostacyclin) is a lipid mediator with vasodilatory and antithrombotic effects used in the treatment of vasoconstrictive/ischemic diseases including pulmonary artery hypertension. However, emerging research supports a role for PGs, including PGI2, in the regulation of both innate and acquired immunity. As PGI2 is unstable, we sought to define the effects of various PGI2 analogs on resident alveolar macrophage (AM) and peritoneal macrophage (PM) innate immune functions. The effects of iloprost, carbaprostacyclin, and treprostinil on the regulation of phagocytosis, bacterial killing, and inflammatory mediator production were determined in both macrophage populations from rats. Iloprost failed to suppress AM functions to the same degree that it did in PMs, a characteristic shared by carbaprostacyclin. This difference reflected greater expression of the Gαs protein-coupled I prostanoid receptor and greater cAMP generation in PMs than AMs. Treprostinil inhibited phagocytosis, bacterial killing, and cytokine generation in AMs to a much greater degree than the other PGI2 analogs and more closely resembled the effects of PGE2. Studies with the E prostanoid (EP) 2 receptor antagonist AH-6809 and EP2-null macrophages indicated that this was due in part to the previously unknown ability of treprostinil to stimulate the EP2 receptor. The present investigation for the first time identifies differences in immunoregulatory properties of clinically administered PGI2 analogs. These studies are the first to explore the capacity of PGI2 to regulate bacterial killing and phagocytosis in macrophages, and our findings may hold important consequences regarding the risk of infection for patients receiving such agents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Aronoff

Peres

Serezani

et al. 2007

The Journal of Immunology

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“…25) It has been shown previously that hyperglycemia induces increased adhesion of leukocytes (especially monocytes) to endothelial cells as an early event in atherosclerosis and certain in‰ammatory disorders in diabetes-induced endothelial dysfunction. 26) Inhibition of adhesion of monocytes is a pharmacological approach to attenuate hyperglycemia-induced vascular in‰ammatory disorders.…”

Section: Ešects Of Scutellarin On Monocyte-endothelial Cell Adhesion mentioning

confidence: 99%

Scutellarin Isolated from <i>Erigeron multiradiatus</i> Inhibits High Glucose-mediated Vascular Inflammation

et al. 2008

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Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to in‰ammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known ‰avone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular in‰ammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 mM) reversed these eŠects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce signiˆcant antihyperglycemic action, it lowered the serum MCP-1 levels signiˆcantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-in‰ammation eŠect that may aŠord some protection against hyperglycemiainduced vascular in‰ammatory both in vitro and in vivo.

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“…Endotheliumderived PGI 2 also plays a role in maintaining a healthy endothelium and regulating EC function (Zardi et al, 2005). Beraprost increases EC barrier integrity by promoting cortical F-actin ring formation and inhibiting central stress fibers at areas covered by adherens junctions, a process mediated via Rac1 and its effector p21-activated kinase, and effectively counteracts the stimulatory effects of RhoA/Rho-associated protein kinase on stress fiber formation (Birukova et al, 2007 -independent signaling pathways.…”

Section: A Effects Of Prostacyclin On Endothelial Cellsmentioning

confidence: 99%

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

2012

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Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs

Cited by 41 publications

References 240 publications

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Scutellarin Isolated from <i>Erigeron multiradiatus</i> Inhibits High Glucose-mediated Vascular Inflammation

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

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