Honors Theses


Carissa M. Krane, Ph.D.



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Honors Thesis


Background: Aquaporins (AQPs) are transmembrane water channels that facilitate osmotically-driven transmembrane water flux. AQP1 is abundantly expressed in vascular endothelium, where it functions in endothelial cell migration, wound healing, and cell volume regulation in response to mechanical stimuli. AQP1 protein abundance is enhanced in cultured human umbilical vein endothelial cells (HUVECs) in response to fluid shear stress. Statins, a pharmacological class of HMG-CoA reductase inhibitors, suppress the early development of vein graft intimal hyperplasia by improving endothelial cell function, most likely by affecting endothelial response to arterial shear stress. Statins may also differentially regulate the expression of specific AQPs by altering their abundance and/or subcellular localization. Therefore, it is hypothesized that AQP1 may function as a component of the mechanosensory complex in endothelial cells and therefore is subject to shear stress-induced gene regulation and modulation of expression by statins.

Methods: HUVECs were cultured in microfluidic chambers under static (0 dynes/cm2) and venous fluid shear stress (6 dynes/cm2) in the presence or absence of 5 μM Pravastatin™. Fluorescent immunocytochemistry was used to detect AQP1 protein expression. Images were captured using confocal laser scanning microscopy. Mean fluorescent intensity (in arbitrary units) was determined using ImageJ software and normalized to control conditions (time zero, static culture with no Pravastatin™). Twenty-five to thirty cells from two independent experiments were analyzed for each experimental condition.

Results: AQP1 expression increased 1.4-fold (p<0.05) after 24 hours, and 1.5-fold (p<0.05) after 48 hours in cells cultured under venous fluid shear stress as compared to the control. This shear stress-induced expression was blocked by incubation with Pravastatin™ and reduced by 27% (p<0.05; control vs. venous shear stress with Pravastatin™). Pravastatin™ had no effect on AQP1 expression in static cultures (p>0.05 vs. control). These data indicate that Pravastatin™ suppresses shear stress dependent induction of AQP1 in cultured HUVECs.

Conclusions: Results show that the shear stress-dependent induction of AQP1 protein expression is suppressed by Pravastatin™. Results further demonstrate a potential function of statin drugs in regulating the expression of AQPs that is both independent of their cholesterol-lowering function and related to the regulation of AQP1 in vascular endothelial cells.

Funding Sources: This research was funded by the Schuellein Chair in the Biological Sciences (CMK), University Honors Program of the University of Dayton (RJC), and a 2015 American Physiological Society Summer Undergraduate Research Fellowship Award to RJC.

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Undergraduate research


Biology | Life Sciences

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