Related Experiment Video
Updated: Jul 5, 2026

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
Counter regulatory effects of PKCbetaII and PKCdelta on coronary endothelial permeability
Nathalie Gaudreault1, Rachel M Perrin, Mingzang Guo
1Department of Surgery, University of California Davis School of Medicine, 4625 2nd Avenue, Room 3006, Sacramento, CA 95817, USA.
Objective:
The aim of this study was to examine the endothelial distribution and activity of selected PKC isoforms in coronary vessels with respect to their functional impact on endothelial permeability under the experimental conditions relevant to diabetes.
Methods And Results:
En face immunohistochemistry demonstrated a significant increase of PKC(betaII) and decrease of PKCdelta expression in coronary arterial endothelium of Zucker diabetic rats. To test whether changes in PKC expression alter endothelial barrier properties, we measured the transcellular electric resistance in human coronary microvascular endothelial monolayers and found that either PKC(betaII) overexpression or PKCdelta inhibition disrupted the cell-cell adhesive barrier. Three-dimensional fluorescence microscopy revealed that hyperpermeability was caused by altered PKC activity in association with distinct translocation of PKC(betaII) to the cell-cell junction and PKCdelta localization to the cytosol. Further analyses in fractionated endothelial lysates confirmed the differential redistribution of these isozymes. Additionally, FRET analysis of PKC subcellular dynamics demonstrated a high PKC(betaII) activity at the cell surface and junction, whereas PKCdelta activity is concentrated in intracellular membrane organelles.
Conclusions:
Taken together, these data suggest that PKC(betaII) and PKCdelta counter-regulate coronary endothelial barrier properties by targeting distinctive subcellular sites. Imbalanced PKC(betaII)/PKCdelta expression and activity may contribute to endothelial hyperpermeability and coronary dysfunction in diabetes.
More Related Videos
Related Concept Videos
Pharmacokinetic–Pharmacodynamic Relationship: Exposure, Response and Effect
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
cAMP-dependent Protein Kinase Pathways
Pharmacokinetic–Pharmacodynamic Relationship: Model Components
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

