Abstract
Background: Intracranial aneurysms (IAs) result from abnormal enlargement of the arterial lumen. IAs are mostly quiescent and asymptomatic, but their rupture leads to severe brain damage or death. As the evolution of IAs is hard to predict and intricates medical decision, it is essential to improve our understanding of their pathophysiology. Wall shear stress (WSS) is proposed to influence IA growth and rupture. In this study, we investigated the effects of low and supra-high aneurysmal WSS on endothelial cells (ECs).Methods: Porcine arterial ECs were exposed for 48 h to defined levels of shear stress (2, 30, or 80 dyne/cm2) using an Ibidi flow apparatus. Immunostaining for CD31 or γ-cytoplasmic actin was performed to outline cell borders or to determine cell architecture. Geometry measurements (cell orientation, area, circularity and aspect ratio) were performed on confocal microscopy images. mRNA was extracted for RNAseq analysis.Results: ECs exposed to low or supra-high aneurysmal WSS were more circular and had a lower aspect ratio than cells exposed to physiological flow. Furthermore, they lost the alignment in the direction of flow observed under physiological conditions. The effects of low WSS on differential gene expression were stronger than those of supra-high WSS. Gene set enrichment analysis highlighted that extracellular matrix proteins, cytoskeletal proteins and more particularly the actin protein family were among the protein classes the most affected by shear stress. Interestingly, most genes showed an opposite regulation under both types of aneurysmal WSS. Immunostainings for γ-cytoplasmic actin suggested a different organization of this cytoskeletal protein between ECs exposed to physiological and both types of aneurysmal WSS.Conclusion: Under both aneurysmal low and supra-high WSS the typical arterial EC morphology molds to a more spherical shape. Whereas low WSS down-regulates the expression of cytoskeletal-related proteins and up-regulates extracellular matrix proteins, supra-high WSS induces opposite changes in gene expression of these protein classes. The differential regulation in EC gene expression observed under various WSS translate into a different organization of the ECs’ architecture. This adaptation of ECs to different aneurysmal WSS conditions may affect vascular remodeling in IAs.
Highlights
Intracranial aneurysms (IAs) resulting from the deformation and enlargement of the lumen in arteries of the circle of Willis affect three to five percent of the population (Lawton and Vates, 2017)
Wall shear stress (WSS) defined as the tangential force per unit area imposed by the blood flow on the arterial wall per unit area is sensed by endothelial cells (ECs)
ECs exposed to either type of aneurysmal WSS (2 or 80 dyne/cm2) failed to elongate (Figure 1A—left and right)
Summary
Intracranial aneurysms (IAs) resulting from the deformation and enlargement of the lumen in arteries of the circle of Willis affect three to five percent of the population (Lawton and Vates, 2017). In human IAs, low WSS close to 2 dyne/cm is typically observed in wide-neck aneurysms with a slow recirculating flow whereas supra-high WSS (> 70 dyne/cm2) is found in aneurysms with impinging jet flow (Meng et al, 2014; Munarriz et al, 2016; Staarmann et al, 2019) These aneurysmal flow patterns affect IA pathophysiology: while low WSS seems to promote atherosclerotic, inflammatory and thrombotic processes, supra-high WSS has been associated with smooth muscle cell phenotypic changes and apoptosis (Meng et al, 2014; Munarriz et al, 2016; Cebral et al, 2019; Frosen et al, 2019; Staarmann et al, 2019). We investigated the effects of low and supra-high aneurysmal WSS on endothelial cells (ECs)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
