Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells

• Published in: Journal of cellular physiology Vol. 233; no. 1; pp. 186 - 200
• Main Authors: Wilkinson, Emma L., Sidaway, James E., Cross, Michael J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018; John Wiley and Sons Inc
• Subjects: Antibiotics, Antineoplastic - toxicity; Capillary Permeability - drug effects; Cardiotoxicity; Cell activation; Cell permeability; Cells, Cultured; Coronary Vessels - drug effects; Coronary Vessels - enzymology; Cytoprotection; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - toxicity; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Enzyme Activation; ERK5; Gene expression; Gene silencing; Heart; Heart diseases; Heart Diseases - chemically induced; Heart Diseases - enzymology; Heart Diseases - genetics; Heart Diseases - prevention & control; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Kinases; Localization; Microvasculature; Mitogen-Activated Protein Kinase 7 - genetics; Mitogen-Activated Protein Kinase 7 - metabolism; Original; Original s; Permeability; Pretreatment; Protein Prenylation - drug effects; Protein Transport - drug effects; Quinolines - pharmacology; Reductase; RNA Interference; Rosuvastatin Calcium - pharmacology; Signal Transduction - drug effects; Simvastatin - pharmacology; siRNA; statin; Statins; Tight Junctions - drug effects; Tight Junctions - enzymology; Transfection; Translocation; Zonula occludens-1 protein; Zonula Occludens-1 Protein - metabolism; ZO‐1; cardiotoxicity; ZO-1; statin; ERK5; permeability

The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co‐A reductase inhibitor drugs. We utilized human cardiac microva...