Abstract 360: Molecular and Cellular Dynamics of Merlin in Vascular Cells via Mechanotransduction

Abstract

Endothelial integrity plays a pivotal role in normal blood vessel function and disruption of which will lead to the initiation and progression of atherosclerosis. The actin cytoskeleton which provides endothelial structural integrity can be greatly disrupted by many factors, such as inflammation and haemodynamic forces. Altered actin dynamics underpins many (patho-) physiological processes in endothelial cells such as migration, differentiation, proliferation and adhesion. The ERM (ezrin/radixin/moesin) proteins which belong to erythrocyte 4.1 superfamily are actin adaptor proteins and play an important role in controlling cytoskeleton dynamics. This study focuses on one member of the ERM protein family- Merlin. Merlin (moesin, ezrin and radixin-like protein), has been well characterised as a tumour suppressor, contributing to brain tumours such as schwannoma and meningiomas. However, the role of merlin within the vasculature is poorly understood as is its function in various cellular processes such as migration, proliferation and cell adhesion. In this current study we exposed Human Aortic Endothelial Cells (HAECs), in an in vitro model, to haemodynamic force (i.e. shear stress and cyclic strain) to exam its influence on the temporal and spatial expression of Merlin. We also investigate if Merlin mediates the regulation of Cell-ECM adhesion, migration and proliferation. Results demonstrate that the expression of Merlin is decreased by exposed to haemodynamic force. Furthermore, we have concluded that Merlin knock-down, via siRNA, decreases HAECs adhesion, migration and proliferation as studied in real-time by an xCELLigence system.