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Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study Coronary Microcirculation in Ischemic Heart Disease Evolving understanding of the heterogeneous natural history of individual coronary artery plaques and the role of local endothelial shear stress Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study High Coronary Shear Stress in Patients With Coronary Artery Disease Predicts Myocardial Infarction Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway
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Original Research2018 Feb;233(2):1384-1395.

JOURNAL:J Cell Physiol. Article Link

Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway

Chao Y, Ye P, Chen SL et al. Keywords: angiotensin II type 1 receptor; eNOS uncoupling; low shear stress; nitric oxide; reactive oxygen species

ABSTRACT


Reactive oxygen species (ROS) contribute to many aspects of physiological and pathological cardiovascular processes. However, the underlying mechanism of ROS induction by low shear stress (LSS) remains unclear. Accumulating evidence has shown that the angiotensin II type 1 receptor (AT1R) is involved in inflammation, apoptosis, and ROS production. Our aim was to explore the role of AT1R in LSS-mediated ROS induction. We exposed human umbilical vein endothelial cells (HUVECs) to LSS (3 dyn/cm2 ) for different periods of time. Western blotting and immunofluorescence showed that LSS significantly induced AT1R expression in a time-dependent manner. Using immunohistochemistry, we also noted a similar increase in AT1R expression in the inner curvature of the aortic arch compared to the descending aorta in C57BL/6 mice. Additionally, HUVECs were cultured with a fluorescent probe, either DCFH, DHE or DAF, after being subjected to LSS. Cell chemiluminescence and flow cytometry results revealed that LSS stimulated ROS levels and suppressed nitric oxide (NO) generation in a time-dependent manner, which was reversed by the AT1R antagonist Losartan. We also found that Losartan markedly increased endothelial NO synthase (eNOS) phosphorylation at Ser(633,1177) and dephosphorylation at Thr(495), which involved AKT and ERK. Moreover, the ROS level was significantly reduced by endogenous and exogenous NO donors (L-arginine, SNP) and increased by the eNOS inhibitor L-NAME. Overall, we conclude that LSS induces ROS via AT1R/eNOS/NO.