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Endothelial Cell Transcytosis Assay as an In Vitro Model to Evaluate Inner Blood-Retinal Barrier Permeability
Published on: June 7, 2022
Protein kinase C-beta inhibition and diabetic microangiopathy: effects on endothelial permeability responses in vitro
Iskandar Idris1, Samuel Gray, Richard Donnelly
1Centre for Integrated Systems Biology and Medicine, School of Medical and Surgical Sciences, University of Nottingham, Nottingham, UK.
Abstract:
Protein kinase C (PKC)-beta and other PKC isozymes have been implicated in the loss of endothelial barrier function in diabetic microangiopathy. The effects of a PKC-beta-specific inhibitor, LY379196, on hyperpermeability responses to high-glucose, angiotensin II, alpha-thrombin and endothelin-1 were evaluated using an in vitro model of human pulmonary artery endothelial cell monolayers. LY379196 attenuated the increase in transendothelial albumin flux induced by glucose 40 mM (e.g. 411+/-160% [high-glucose] vs. 167+37% [high-glucose+LY379196], P<0.001) and angiotensin II 10 microM (e.g. 121+/-12% vs. 246+/-35%, P<0.01); endothelin-1 had no significant effect on monolayer permeability. LY379196 had no significant effect on the marked hyperpermeability response to alpha-thrombin 1 microM. Thus, two major pathways involved in vascular leakage in diabetic microangiopathy are amenable to therapeutic blockade by PKC-beta inhibition.
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