Title

Assessing the effect of shear stress, statin on aquaporin 1 expression in vascular endothelial cells in vitro

Author

Kyle McGrail

Date of Award

2016

Degree Name

M.S. in Biology

Department

Department of Biology

Advisor/Chair

Advisor: Carissa M. Krane

Abstract

The human saphenous vein (HSV) is commonly used in coronary artery bypass grafts. The patency of the vein graft in an arterial environment is limited, thereby requiring a high percentage of autograft recipients to repeat the bypass surgery within 5 years. The main problem that ensues with HSV grafts is due to the development of intimal hyperplasia (IH) which compromises vessel function. The mechanistic reasons for the development of IH and limited HSV patency are not currently understood. However, it has been proposed that the change from venous to arterial shear stress may be a trigger. Aquaporin 1 (AQP1), a water channel protein, is expressed in the plasma membrane of vascular endothelial cells. It is hypothesized that enhanced AQP1 expression may be an early biomarker for the development of IH. It is also well known that statins, a group of cholesterol lowering drugs that reduce the progression of atherosclerosis may also function to prevent or lessen the development of IH in these grafts. However, the process(es) by which 1.) IH is triggered in the HSV grafts, and 2.) statins may help to prevent the development of IH is currently unknown. The goal of this study was to assess the effect of shear stress and statins on AQP1 expression in cultured endothelial cells. Primary vascular endothelial cells seeded on a gelatin-coated Ibidi flow chamber grown in static conditions express low levels of AQP1 protein that localizes around the nucleus. AQP1 was present in vesicles throughout the cytoplasm in increasing abundance in cells subjected to low shear stress (6 dynes/cm², venous flow) and high shear stress (16 dynes/cm², arterial flow (p<0.05). In static cultures in the presence of pravastatin", the expression of AQP1 decreases when compared static cultures not incubated with pravastatin (p<0.05). As a consequence, pravastatin may target and control AQP1 expression, thereby preventing the development of IH. As a result of changes in shear stress, AQP1 translocation from perinuclear expression to the membrane could be the likely response to environmental change that triggers cellular response for IH. As a consequence, statins may target and control AQP1 expression, thereby preventing the development of IH. The main focus of this research on endothelial cells is to understand the implications of how aquaporin expression and function in endothelial cells may contribute to the initiation of intimal hyperplasia in grafted HSVs, which can eventually lead to graft failures."

Keywords

Aquaporins, Vascular endothelial cells, Shear flow, Statins (Cardiovascular agents), Intimal hyperplasia, Physiology, Aquaporins

Rights Statement

Copyright 2016, author

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