CHARACTERIZING ENDOTHELIAL NOTCH1 RELEASE IN RESPONSE TO CHANGES IN VASCULAR WALL SHEAR STRESS
Date of Award
Atherosclerosis, Cardiovascular disease, Endothelium, Mechanosensor, Notch1, Shear stress
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Murine and cell culture models have identified Notch1 as a novel endothelial mechanosensor that may exert a protective role for vascular adjustments in response to changes in vascular wall shear stress. However, in vivo studies in humans are lacking. Accordingly, we sought to characterize the concentrations of Notch1 extracellular domain (ECD) prior to, during, and following 20-min of altered shear stress in the brachial artery of ten young and healthy adults (6M/4F). Alterations in shear were induced by placing a pneumatic cuff inflated to 220mmHg around the left wrist. Cuffs were also placed below the axilla of both arms and inflated to 40mmHg to trap the released Notch1 ECD. The right arm (no wrist cuff) was treated as a time control. Blood samples were collected from a superficial antecubital vein of both arms at baseline, 20-min of wrist cuff inflation, as well as 1-min and 15-min following wrist cuff release. The Notch1 ECD was quantified from plasma using a commercially available ELISA kit. Duplex ultrasound was used to confirm alterations in shear stress. In the experimental arm, concentrations of Notch1 ECD remained statistically similar to baseline values following 20-min of reduced antegrade shear stress, but were significantly elevated by ~50% (P=0.033) immediately following cuff release, coinciding with a ~100% increase in antegrade shear. Concentrations of Notch1 ECD remained unchanged in the control arm and were statistically similar to baseline values at 15 min recovery in both the control and experimental arm. These data indicate that Notch1 may be an important mechanistic regulator of vascular function, particularly in response to increased antegrade shear.
Badour, Matthew Indiana, "CHARACTERIZING ENDOTHELIAL NOTCH1 RELEASE IN RESPONSE TO CHANGES IN VASCULAR WALL SHEAR STRESS" (2022). Electronic Theses and Dissertations. 8908.