Journal ArticleDOI
Effects of Flow Patterns on the Localization and Expression of VE-Cadherin at Vascular Endothelial Cell Junctions: In vivo and in vitro Investigations
Hui Miao,Ying Li Hu,Yan-Ting Shiu,Suli Yuan,Yihua Zhao,Roland Kaunas,Yingxiao Wang,Gang Jin,Shunichi Usami,Shu Chien +9 more
TLDR
The findings suggest that the cell junction remodeling induced by different flow patterns may result from a redistribution of VE-cadherin within the cell membrane.Abstract:
Atherosclerosis occurs preferentially at vascular curvature and branch sites where the vessel walls are exposed to fluctuating shear stress and have high endothelial permeability. Endothelial permeability is modulated by intercellular adhesion molecules such as VE-cadherin. This study was designed to elucidate the effects of different flow patterns on the localization and expression of VE-cadherin in endothelial cells (ECs) both in vivo and in vitro. VE-cadherin staining at EC borders was much stronger in the descending thoracic aorta and abdominal aorta, where the pulsatile flow has a strong net forward component than in the aortic arch and the poststenotic dilatation site beyond an experimental constriction, where the flow near the wall is complex and reciprocating with little net flow. With the use of flow chambers the effects of pulsatile flow (12 +/- 4 dyn/cm2 at 1 Hz) and reciprocating flow (0.5 +/- 4 dyn/cm2 at 1 Hz) on VE-cadherin organization in endothelial monolayers were studied in vitro. VE-cadherin staining was continuous along cell borders in static controls. Following 6 h of either pulsatile or reciprocating flow, the VE-cadherin staining at cell borders became intermittent. When the pulsatile flow was extended to 24, 48 or 72 h the staining around the cell borders became continuous again, but the staining was still intermittent when the reciprocating flow was similarly extended. Exposure to pulsatile or reciprocating flow for 6 and 24 h neither change the expression level of VE-cadherin nor its distribution between membrane and cytosol fractions as determined by Western blot and compared with static controls. These findings suggest that the cell junction remodeling induced by different flow patterns may result from a redistribution of VE-cadherin within the cell membrane. Both the in vivo and in vitro data indicate that pulsatile and reciprocating flow patterns have different effects on cell junction remodeling. The lack of junction reorganization in regions of reciprocating flow in vivo and in vitro may provide a mechanistic basis for the high permeability and the preferential localization of atherosclerosis in regions of the arterial stress with complex flow patterns and fluctuating shear stress.read more
Citations
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Journal ArticleDOI
Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives
Jeng Jiann Chiu,Shu Chien +1 more
TL;DR: Current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications are summarized to contribute to the understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
Journal ArticleDOI
MicroRNA Regulation of Atherosclerosis.
TL;DR: Current paradigms of miRNA-mediated effects in atherosclerosis progression and regression are highlighted, and an update on the potential use of miRNAs diagnostically for detecting increasing severity of coronary disease and clinical events is provided.
Journal ArticleDOI
Molecular Biology of Atherosclerosis
TL;DR: Key signaling pathways are presented to provide a context for the gene manipulations summarized herein and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.
Journal ArticleDOI
Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow
Li Wang,Jiang-Yun Luo,Bochuan Li,Xiao Yu Tian,Li-Jing Chen,Yuhong Huang,Jian Liu,Dan Deng,Chi Wai Lau,Song Wan,Ding Ai,Kinglun Kingston Mak,Ka Kui Tong,Kin Ming Kwan,Nanping Wang,Jeng-Jiann Chiu,Yi Zhu,Yu Huang +17 more
TL;DR: The results indicate that integrin–Gα13–RhoA–YAP pathway holds promise as a novel drug target against atherosclerosis.
Journal ArticleDOI
Effects of Disturbed Flow on Endothelial Cells
TL;DR: Understanding of the EC responses to different flow patters helps to elucidate the mechanism of the region-specific localization of atherosclerosis in the arterial system.
References
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