Document Type

Research Poster

Publication Date

2014

Abstract

Blood flow feeding tissues and organs is closely regulated in order to meet metabolic and functional needs. Control of blood flow is accomplished by regulating the diameter of the arteries and arterioles feeding different organs. Several neural, hormonal, chemical and mechanical mechanisms contribute to the constriction and dilation of arteries. Shear stress, the frictional force created by streaming blood on the endothelial layer of arteries, is one of these mechanical mechanisms (1). Shear stress causes both acute and long term effects on endothelial cells (1,2,5).

Blood in arteries typically flows away from the heart towards organs (causing antegrade shear stress) during cardiac contraction and briefly flows back toward the heart (causing retrograde shear stress) during cardiac filling. Retrograde flow occurs more often in some disease situations, and studies have shown that retrograde shear stress decreases endothelial cell function (3,4). The specific mechanisms for endothelial dysfunction are unknown, but altered mechanisms could include impaired cell signaling pathways. The most important endothelial cell dilatory signaling pathway is the production of nitric oxide (NO). Retrograde shear stress causes endothelial cells to secrete NO, and increased rates of shear stress cause increased expression and phosphorylation of nitric oxide synthase (eNOS). Regulatory phosphorylation of eNOS can potentially occur on at least four sites: Ser 1177, Ser 116, Ser 635 and Thr 497 (3). The most well characterized of these is Ser 1177, which is phosphorylated by a by PI3K/AKT shear dependent pathway. Regulating phosphorylation of eNOS is critical to endothelial health and maintaining cardiovascular equilibrium. Using rat soleus muscle feed arteries, we seek to determine the effects of changes in shear stress direction on both endothelial cell function and phosphorylation of eNOS at the Ser 1177 site.

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