Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA330

Poster Communications

Vascular Scrib Limits Atherosclerosis by Maintaining Arterial Integrity

C. Schürmann1,2, F. Dienst1, E. Vasconez1, K. Pálfi1, J. A. Oo1, F. Hahner1, S. Wang3, S. Offermanns3, M. S. Leisegang1,2, C. Kruse1, R. Brandes1,2

1. Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany. 2. Partner site RheinMain, German Center for Cardiovascular Research, Frankfurt, Germany. 3. Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

The polarity protein Scrib contributes to planar cell polarity. Because endothelial Scrib facilitates endothelial inflammatory signaling, we hypothesized that Scrib contributes to atherosclerosis development. Spontaneous atherosclerosis development was determined in tamoxifen-inducible Scrib conditional knockout (KO) mice, crossed into ApoE KO mice, under high fat diet (HFD). Accelerated atherosclerosis was determined in the partial carotid artery ligation model during HFD treatment. Deletion of Scrib resulted in increased vascular lumen loss in the partial ligation model. Similarly, spontaneous atherosclerosis-development was accelerated in the brachiocephalic trunk of Scrib ApoE double KO animals compared to Cre negative littermates. Mechanistically, Scrib KO decreased acetylcholine- as well as flow-induced vascular relaxation of isolated arteries and flow-induced AKT-phosphorylation of carotid endothelial cells (CEC). As determined by next generation sequencing of CEC, knockout of Scrib reduced the expression of eNOS, shear stress-responsive genes and of cell adhesion molecules. In line with altered cell adhesion, basal lung permeability to Evans blue was increased in endothelial specific Scrib deficient mice. Immune cell extravasation into the lung was elevated after endothelial specific Scrib KO (2h LPS treatment). Conclusion: Scrib maintains arterial integrity and has anti-atherosclerotic functions.

Where applicable, experiments conform with Society ethical requirements