Updates on Endothelial Functions of Proangiogenic Prokineticin

Nebigil, Canan G.

doi:10.1161/hypertensionaha.116.08037

Cited by 4 publications

(3 citation statements)

References 64 publications

(76 reference statements)

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“…It has been shown that exogenous TIMP-1 prevents endothelial cell apoptosis through the activation of cell survival pathways [43]. Furthermore, the aorta of endothelial-specific prokineticin receptor-1 deficient mice displayed progressive impairment of ACh mediated endothelium-dependent relaxation, because of decreased nitric oxide synthesis [44]. It should also be mentioned that both pro-apoptotic and anti-apoptotic proteins were detected in the CM.…”

Section: Mechanisms Underlying the Vascular Protective Effects Of CM After Ir Injury When Using Vascular Grafts From Bd Donorsmentioning

confidence: 99%

Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

et al. 2021

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Background Brain death (BD) has been suggested to induce coronary endothelial dysfunction. Ischemia/reperfusion (IR) injury during heart transplantation may lead to further damage of the endothelium. Previous studies have shown protective effects of conditioned medium (CM) from bone marrow-derived mesenchymal stem cells (MSCs) against IR injury. We hypothesized that physiological saline-supplemented CM protects BD rats’ vascular grafts from IR injury. Methods The CM from rat MSCs, used for conservation purposes, indicates the presence of 23 factors involved in apoptosis, inflammation, and oxidative stress. BD was induced by an intracranial-balloon. Controls were subjected to a sham operation. After 5.5 h, arterial pressures were measured in vivo. Aortic rings from BD rats were harvested and immediately mounted in organ bath chambers (BD group, n = 7) or preserved for 24 h in 4 °C saline-supplemented either with a vehicle (BD-IR group, n = 8) or CM (BD-IR+CM group, n = 8), prior to mounting. Vascular function was measured in vitro. Furthermore, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) have been performed. Results BD in donors was associated with significantly impaired hemodynamic parameters and higher immunoreactivity of aortic myeloperoxidase (MPO), nitrotyrosine, caspase-3, caspase-8, caspase-9, and caspase-12 compared to sham-operated rats. In organ bath experiments, impaired endothelium-dependent vasorelaxation to acetylcholine in the BD-IR group compared to BD rats was significantly improved by CM (maximum relaxation to acetylcholine: BD 81 ± 2% vs. BD-IR 50 ± 3% vs. BD-IR + CM 72 ± 2%, p < 0.05). Additionally, the preservation of BD-IR aortic rings with CM significantly lowered MPO, caspase-3, caspase-8, and caspase-9 immunoreactivity compared with the BD-IR group. Furthermore, increased mRNA expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the aortas from the BD-IR rats compared to BD group were significantly decreased by CM. Conclusions The preservation of BD rats’ vascular grafts with CM alleviates endothelial dysfunction following IR injury, in part, by reducing levels of inflammatory response and caspase-mediated apoptosis.

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Section: Mechanisms Underlying the Vascular Protective Effects Of CM After Ir Injury When Using Vascular Grafts From Bd Donorsmentioning

confidence: 99%

Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

et al. 2021

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“…In ECs cultured in vitro, activation of PKR2, unlike PKR1, does not induce angiogenesis but couples to G α 12-13-mediated degradation of zonula occludens one, a cell-cell adhesion molecule, at tight junctions and forms a fenestration of ECs. PKR1 expression is dominant in the physiologic state, whereas PKR2 becomes dominant upon pathologic stimuli ( Guilini et al, 2010 ; Nebigil, 2016 ).…”

Section: Role Of the Prokineticins In Cardiovascular Diseasesmentioning

confidence: 99%

Therapeutic Potential of Targeting Prokineticin Receptors in Diseases

Vincenzi,

Kremić,

Jouve

et al. 2023

Pharmacol Rev

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The prokineticins (PKs) were discovered approximately 20 years ago as small peptides inducing gut contractility. Today, they are established as angiogenic, anorectic, and proinflammatory cytokines, chemokines, hormones, and neuropeptides involved in variety of physiologic and pathophysiological pathways. Their altered expression or mutations implicated in several diseases make them a potential biomarker. Their G-protein coupled receptors, PKR1 and PKR2, have divergent roles that can be therapeutic target for treatment of cardiovascular, metabolic, and neural diseases as well as pain and cancer. This article reviews and summarizes our current knowledge of PK family functions from development of heart and brain to regulation of homeostasis in health and diseases. Finally, the review summarizes the established roles of the endogenous peptides, synthetic peptides and the selective ligands of PKR1 and PKR2, and nonpeptide orthostatic and allosteric modulator of the receptors in preclinical disease models. The present review emphasizes the ambiguous aspects and gaps in our knowledge of functions of PKR ligands and elucidates future perspectives for PK research. Significance Statement This review provides an in-depth view of the prokineticin family and PK receptors that can be active without their endogenous ligand and exhibits “constitutive” activity in diseases. Their non- peptide ligands display promising effects in several preclinical disease models. PKs can be the diagnostic biomarker of several diseases. A thorough understanding of the role of prokineticin family and their receptor types in health and diseases is critical to develop novel therapeutic strategies with safety concerns.

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“…This effect may be attributed to the autocrine/paracrine mode of action of the prokineticin ligand, which might be secreted under normal conditions to maintain normal physiological cell function. By antagonizing the receptors, we may be able to prevent the aberrant, non-physiological actions of the prokineticin system [56][57][58][59][60].…”

Section: Effect Of Proks and Prokrs' Antagonists On Bbbmentioning

confidence: 99%

Effects of Prokineticins on Cerebral Cell Function and Blood–Brain Barrier Permeability

Younes,

Kyritsi,

Mahrougui

et al. 2023

IJMS

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Prokineticins are a family of small proteins with diverse roles in various tissues, including the brain. However, their specific effects on different cerebral cell types and blood–brain barrier (BBB) function remain unclear. The aim of this study was to investigate the effects of PROK1 and PROK2 on murine cerebral cell lines, bEnd.3, C8.D30, and N2a, corresponding to microvascular endothelial cells, astrocytes and neurons, respectively, and on an established BBB co-culture model. Western blot analysis showed that prokineticin receptors (PROKR1 and PROKR2) were differentially expressed in the considered cell lines. The effect of PROK1 and PROK2 on cell proliferation and migration were assessed using time-lapse microscopy. PROK1 decreased neural cells’ proliferation, while it had no effect on the proliferation of endothelial cells and astrocytes. In contrast, PROK2 reduced the proliferation of all cell lines tested. Both PROK1 and PROK2 increased the migration of all cell lines. Blocking PROKRs with the PROKR1 antagonist (PC7) and the PROKR2 antagonist (PKR-A) inhibited astrocyte PROK2-mediated migration. Using the insert co-culture model of BBB, we demonstrated that PROKs increased BBB permeability, which could be prevented by PROKRs’ antagonists.

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Updates on Endothelial Functions of Proangiogenic Prokineticin

Cited by 4 publications

References 64 publications

Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

Therapeutic Potential of Targeting Prokineticin Receptors in Diseases

Effects of Prokineticins on Cerebral Cell Function and Blood–Brain Barrier Permeability

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