Title: Effect of low shear stress on permeability and occludin expression in porcine artery endothelial cells Authors
|Conklin, Brian - BAYLOR COLLEGE OF MED|
|Vito, Raymond - SCHOOL OF MECHANICAL E|
|Chen, Changyi - MOLECULAR SURGEON RESE|
Submitted to: World Journal of Surgery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 8, 2007
Publication Date: March 8, 2007
Citation: Conklin, B.S., Vito, R.P., Chen, C. 2007. Effect of low shear stress on permeability and occludin expression in porcine artery endothelial cells. World Journal of Surgery. 31:733-743. Interpretive Summary: There is a well-known correlation between certain blood flow patterns, namely low wall shear stress, and the development of atherosclerotic arterial disease, which can lead to heart attack and stroke. One of the early hallmarks of atherosclerosis is the accumulation of cholesterol in the blood vessel wall. This research investigated the effects of blood flow patterns on the ability of the vascular wall to exclude cholesterol-size particles. The results demonstrated that low wall shear stress correlated with an increase in the accumulation of these particles within the vascular wall and corresponding changes in proteins that could help explain this change. These results may provide a better understanding of the atherosclerotic disease process and help lead to improved prevention strategies.
Technical Abstract: INTRODUCTION: Although both fluid shear stress and mass transport of atherogenic substances into the vascular wall are known to be important factors in atherogenesis, there has been little research on the effect of shear stress on vascular permeability. Therefore, the effects of shear stress on the permeability of arteries and the expression of the endothelial cell tight junction molecule occludin, an important regulator of vascular permeability, were investigated. METHODS: Porcine carotid arteries were perfusion cultured ex vivo with low (1.5 dyne/cm(2)) or physiologic (15 dyne/cm(2)) shear stress and 100 mmHg pressure for 24 hours. Subsequently, 20 nm gold particles in solution were infused into the lumen of vessels at 100 mmHg for 30 minutes. Frozen sections were then cut and stained for gold particles. Image analysis was used to determine the density of the particles in the vessel walls. The expression of endothelial cell occludin mRNA and protein were determined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: Permeability results showed a 2.8-fold increase in the apparent permeability of vessels cultured with low versus physiologic shear stress. RT-PCR and Western blotting results showed significant decreases in occludin mRNA and protein expression at 12 and 24 hours in vessels cultured with low versus physiologic shear stress. CONCLUSIONS: These results demonstrate that low shear stress increases vascular permeability in porcine carotid arteries, possibly owing to decreased occludin expression. These results may have implications in the preferential formation of atherosclerotic vascular disease adjacent to branches and bifurcations where low mean shear stresses may occur.