Assessing the Pleiotropic Role of Pravastatin TM on the Expression of AQP1 in Vascular Endothelial Cells Cultured under Static, Venous, and Arterial Flow Conditions in vitro

The current surgical procedure to address coronary artery disease (CAD) involves the grafting of the human saphenous vein (HSV) into an arterial environment in the heart in a process called a coronary artery bypass graft (CABG). However, a high percentage of HSV grafts fail within five years due to the development of intimal hyperplasia (IH). The trigger for IH development is currently unknown. It is possible that difference in exposure to venous vs. arterial shear stress plays a role. Statins, a class of cholesterol lowering drugs, have been shown to suppress the early development of IH. Statins have also been shown to differentially regulate the expression of some members of the aquaporin water channel family of transmembrane proteins. Preliminary results suggest that the expression of aquaporin 1 (AQP1), a water channel abundantly expressed in vascular endothelium, is regulated in part by changes in shear stress in human umbilical vein endothelial cells (HUVECs) in vitro . Based on these observations, it is hypothesized that AQP1 may function as an early environmental sensor in HSV grafts to promote IH development, and therefore, may be a novel target for the early intervention and prevention of IH. The aim of this investigation is to determine the effects of changes in shear stress and Pravastatin™ exposure on the gene regulation of AQP1. The time‐dependent effects of venous and arterial shear stress (6 dynes/cm 2 and 16 dynes/cm 2 ) on AQP1 protein expression after 0, 24, 48, and 72 hours of static, venous, and arterial flow conditions were assessed using immunocytochemistry (ICC). The expression of AQP1 mRNA isolated from HUVECs cultured under static and flow conditions for 0, 24, and 48 hours with and without Pravastatin™ was analyzed using qPCR. Combined, the results of these experiments will contribute to an understanding of the relationship between the pleiotropic effects of statins and vascular shear stress and the combinatorial role of the two conditions in the early onset and possible prevention of IH in HSV grafts. Support or Funding Information Support for this research was funded by the 2015 APS Undergraduate Summer Research Fellowship and the University of Dayton Department of Biology.