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A vascular injury model using focal heat-induced activation of endothelial cells.

ABSTRACT: Endothelial cells (EC) both inhibit and promote platelet function depending on their activation state. Quiescent EC inhibit platelet activation by constitutive secretion of platelet inhibitors. Activated EC promote platelet adhesion by secretion of von Willebrand factor (vWF). EC also secrete an extracellular matrix that support platelet adhesion when exposed following vascular injury. Previous studies of EC-platelet interactions under flow activate entire monolayers of cells by chemical activation. In this study, EC cultured in microfluidic channels were focally activated by heat from an underlying microelectrode. Based on finite element modeling, microelectrodes induced peak temperature increases of 10-40 °C above 37 °C after applying 5-9 V for 30 s resulting in three zones: (1) a quiescent zone corresponded to peak temperatures of less than 15 °C characterized by no EC activation or platelet accumulation. (2) An activation zone corresponding to an increase of 16-22 °C yielded EC that were viable, secreted elevated levels of vWF, and were P-selectin positive. Platelets accumulated in the retracted spaces between EC in the activation zone at a wall shear rate of 150 and 1500 s(-1). Experiments with blocking antibodies show that platelets adhere via GPIb?-vWF and ?6?1-laminin interactions. (3) A kill zone corresponded to peak temperatures of greater than 23 °C where EC were not viable and did not support platelet adhesion. These data define heating conditions for the activation of EC, causing the secretion of vWF and the exposure of a subendothelial matrix that support platelet adhesion and aggregation. This model provides for spatially defined zones of EC activation that could be a useful tool for measuring the relative roles of anti- and prothrombotic roles of EC at the site of vascular injury.

SUBMITTER: Sylman JL

PROVIDER: S-EPMC4494879 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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A vascular injury model using focal heat-induced activation of endothelial cells.

Sylman J L JL Artzer D T DT Rana K K Neeves K B KB

Integrative biology : quantitative biosciences from nano to macro 20150701 7

Endothelial cells (EC) both inhibit and promote platelet function depending on their activation state. Quiescent EC inhibit platelet activation by constitutive secretion of platelet inhibitors. Activated EC promote platelet adhesion by secretion of von Willebrand factor (vWF). EC also secrete an extracellular matrix that support platelet adhesion when exposed following vascular injury. Previous studies of EC-platelet interactions under flow activate entire monolayers of cells by chemical activat ...[more]

PMID: 26087748

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Project description:PurposeTo evaluate the mechanical compression of retinal nerve fiber layer (RNFL) by intraretinal cysts in macular edema and its relief with anti-vascular endothelial growth factor (anti-VEGF) treatment.MethodsOptical coherence tomography scans were used to measure RNFL thickness and reflectance at seven preselected points at and around the peak of the edema before and after anti-VEGF treatment in 10 patients (11 eyes) with branch retina vein occlusion (BRVO) and diabetic macular edema (DME). Scans through nonedematous retina and from the fellow eyes were taken as controls. Correlations were sought between the changes in retinal and RNFL thickness, RNFL reflectance, and the size of the intraretinal cysts.ResultsPostinjection RNFL thickness decreased significantly only at peak point of the edema (18.1 ± 2.7 vs. 13.8 ± 1.2 µm; P = 0.038), at its nasal edge (20.1 ± 2.7 vs. 15.5 ± 1.4 µm; P = 0.026), and 500 µm away from its nasal border (35.7 ± 6.0 vs. 20.1 ± 2.7 µm; P = 0.006) suggesting focal stagnation of the axoplasmic flow owing to compression at its peak point. Significant postinjection decreases in RNFL reflectivity were also noted at peak point of the cyst (164.9 ± 10.3 vs. 141.5 ± 12.6 arbitrary units [AU]; P = 0.037), at its nasal edge (166.8 ± 7.8 vs. 135.1 ± 10.2 AU; P = 0.02), and 1500 µm away from temporal edge (160.2 ± 6.2 vs. 141.1 ± 6.4 AU; P = 0.022). Cyst proximity to RNFL (D50 = 50 µm) was the only determinant significantly affecting the magnitude of the RNFL thickness change after anti-VEGF treatment (P = 0.001).ConclusionsIntraretinal cysts due to BRVO and DME locally compress overlying axons and induce anatomic changes suggestive of axoplasmic stagnation. This compression can be relieved with anti-VEGF treatment.Translational relevanceFocal compression of RFNL by retinal cysts may indicate a need for early treatment of macular edema to prevent axonal loss, especially in patients with low axonal reserve.

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A vascular injury model using focal heat-induced activation of endothelial cells.

Publications

A vascular injury model using focal heat-induced activation of endothelial cells.

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