Thrombin Induces Inositol Trisphosphate–Mediated Spatially Extensive Responses in Lung Microvessels

Escue, Rachel; Kandasamy, Kathirvel; Parthasarathi, Kaushik

doi:10.1016/j.ajpath.2016.12.014

Cited by 4 publications

(2 citation statements)

References 63 publications

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“…Previous studies have demonstrated the thrombin-induced permeability increment within Transwell chamber in vivo and observed thrombin-induced organ permeability in vitro (Escue et al, 2017). Clinically, the causal role of thrombin in lung ischemia-reperfusion injury has been established (Farivar et al, 2006).…”

Section: S1pr2 Is Critical To Thrombin-induced Tissue Level Permeability Changesmentioning

confidence: 99%

Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

Zhang

Huang

et al. 2021

Front. Pharmacol.

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Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway.Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro. An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo, an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect.Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance.

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Section: S1pr2 Is Critical To Thrombin-induced Tissue Level Permeability Changesmentioning

confidence: 99%

Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

Zhang

Huang

et al. 2021

Front. Pharmacol.

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“…The propagation of intercellular Ca 2+ waves in the vascular intima can be supported either by the diffusion of cytosolic second messengers [128,139], e.g., Ca 2+ and/or InsP 3 , through gap junctions or by the paracrine release of extracellular mediators [140,141], e.g., ATP. An alternative mechanism has been proposed for the hemodynamic response to prolonged (5 s) somatosensory stimulation in the whisker barrel cortex.…”

Section: Intercellular Ca 2+ Waves In Vascular Endothelial Cellsmentioning

confidence: 99%

Cracking the Endothelial Calcium (Ca2+) Code: A Matter of Timing and Spacing

Moccia,

Brunetti,

Soda

et al. 2023

IJMS

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A monolayer of endothelial cells lines the innermost surface of all blood vessels, thereby coming into close contact with every region of the body and perceiving signals deriving from both the bloodstream and parenchymal tissues. An increase in intracellular Ca2+ concentration ([Ca2+]i) is the main mechanism whereby vascular endothelial cells integrate the information conveyed by local and circulating cues. Herein, we describe the dynamics and spatial distribution of endothelial Ca2+ signals to understand how an array of spatially restricted (at both the subcellular and cellular levels) Ca2+ signals is exploited by the vascular intima to fulfill this complex task. We then illustrate how local endothelial Ca2+ signals affect the most appropriate vascular function and are integrated to transmit this information to more distant sites to maintain cardiovascular homeostasis. Vasorelaxation and sprouting angiogenesis were selected as an example of functions that are finely tuned by the variable spatio-temporal profile endothelial Ca2+ signals. We further highlighted how distinct Ca2+ signatures regulate the different phases of vasculogenesis, i.e., proliferation and migration, in circulating endothelial precursors.

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The Pulmonary Vascular Barrier: Insights into Structure, Function, and Regulatory Mechanisms

Parthasarathi

2017

Molecular and Functional Insights Into the Pulmonary Vasculature

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Pulmonary blood vessels act as a well-regulated barrier to the flux of fluid and solutes between the lumen and the air space. Perturbation of the barrier function results in excessive fluid leak into the interstitium and alveoli, and impairs gas exchange. Recent studies provide deeper insight into the precise control mechanisms involved in the regulation of the barrier. This chapter will highlight these mechanisms and discuss the current understanding on the fluid and solute transport pathways across the vascular endothelial layer. In addition, the chapter summarizes the contributions of extra-endothelial structures such as pericytes and glycocalyx in regulating fluid flux across pulmonary vessels. The chapter concludes with an analysis on the impact of pulmonary endothelial heterogeneity and experimental models on current interpretations of barrier function and regulatory mechanisms.

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Thrombin Induces Inositol Trisphosphate–Mediated Spatially Extensive Responses in Lung Microvessels

Cited by 4 publications

References 63 publications

Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

Cracking the Endothelial Calcium (Ca2+) Code: A Matter of Timing and Spacing

The Pulmonary Vascular Barrier: Insights into Structure, Function, and Regulatory Mechanisms

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