Effects of Exercise‐Induced Shear Stress on Endothelial Gene Expression
Authors: Morales‐Acuna Francisco , Coovert Daniel , Gurovich Alvaro N. 
Published: June 2021

PurposeEndothelial dysfunction is the first step in the development of atherosclerosis and one possible protective regulatory mechanism is exercise‐induced endothelial shear stress. It has been proposed that endurance exercise‐induced shear stress could guide treatment strategies in clinical settings; nevertheless, research on this topic is limited. The aims of this study are (1) to characterize exercise‐induced shear stress patterns and (2) to analyze the effect of simulated exercise‐induce shear stress on endothelial gene expression.MethodsFor the initial in vivo assessment, a total of 12 young healthy subjects (age 13–31) (10 males) were recruited to perform two exercise tests on a cycle ergometer. The first test was a maximal incremental test which established the workloads for the next session, according to blood lactate levels. The second one, performed at least 48 hours after the first exercise test, was a 3 workload steady‐state test at lactate levels of <2 mmol/L (low intensity) for 5 minutes, 2–4 mmol/L (moderate intensity) for 5 minutes, and >4 mmol/L (high intensity) for 3 minutes. Blood flow patterns were recorded during both tests through Doppler ultrasound of the brachial artery (GE Logic E) and shear stress was calculated by Womersley's approximation. In addition, measures of heart rate, oxygen uptake, blood lactate, and rate of perceived exertion (RPE) were obtained at the end of the third minute for each stage. After characterizing exercise‐induced shear stress patterns, in vitro experiments were performed. Cultured human vein endothelial cells (HUVEC) were exposed to anterograde pulsatile flow (OsciFlow Device) in a parallel flow plate (Flex Flow) during 13 hours to simulate resting and exercise conditions: (1) resting shear stress (13 hours at 15 dynes/cm2), (2) low‐to‐moderate shear stress (12 hours at 15 dynes/cm2 followed by 1 hour at 50 dynes/cm2), and (3) high shear stress (12 hours at 15 dynes/cm2 followed by 1 hour at 75 dynes/cm2). Finally, cells were collected and analyzed for pro‐atherogenic VCAM‐1 mRNA expression for each condition. Statistical analysis used one‐way repeated measures ANOVA with Fisher's LSD as post‐hoc analysis. Significance was set at p‐value ≤ 0.05.ResultsAnterograde shear stress showed an intensity‐dependent relationship (rest: 34.7 ± 5.8 dynes/cm2, low: 41.1 ± 13.7 dynes/cm2, moderate: 44.12 ± 17.2 dynes/cm2, and high: 56.96 ± 21.6 dynes/cm2), with significant difference only between low‐to‐moderate intensities vs. high intensity (p < 0.05). Meanwhile, retrograde shear stress exhibited the same intensity trend (rest: 6.9 ± 3.9 dynes/cm2, low: 11.5 ± 5.6 dynes/cm2, moderate: 17.37 ± 9.2 dynes/cm2, and high: 19.6 ± 8.4 dynes/cm2); however, significant differences were seen only between low intensity vs. high‐to‐moderate intensities (p < 0.01). An inverted U shaped curve for VCAM‐1 mRNA expression was observed for resting, low‐to‐moderate, and high simulated shear stress, respectively.ConclusionExercise‐induced shear stress increases in an intensity‐dependent manner. Shear stress observed during high‐intensity exercise might downregulate pro‐atherogenic gene expression on endothelial cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.