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Akihiro Ishibazawa, Taiji Nagaoka, Harumasa Yokota, Youngseok Song, Akitoshi Yoshida; Low Shear Stress Up-Regulates Pro-Inflammatory Gene Expression in Human Retinal Microvascular Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3021. doi: https://doi.org/.
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The vascular endothelium responds to shear stress generated by blood flow and changes functions to regulate blood flow and maintain tissue homeostasis. Recently, we found that physiologic high shear stress leads to increased expression of vasodilatory and antithrombotic genes in human retinal microvascular endothelial cells (HRMECs) (Ishibazawa et al. Invest Ophthalmol Vis Sci, 2011), but the manner in which low shear stress affects retinal endothelial function remains to be elucidated. We studied the effect of low shear stress especially in pro-inflammatory gene expression in HRMECs.
HRMECs cultured on glass plates were exposed to laminar shear stresses of 0 (=static), 1.5 and 15 dyne/cm2 for 24 hours using parallel plate-type flow-loading devises. The mRNA expression of adhesion molecules, cytokines/chemokines, pro-coagulant factors, and cyclooxygenase (COX) were evaluated using real-time reverse-transcriptase polymerase chain reaction.
HRMECs exposed to 1.5 dyne/cm2 significantly up-regulated the mRNA expression of intracellular adhesion molecule-1 (4.2-fold vs static), vascular adhesion molecule-1 (2.5-fold vs static, 4.3-fold vs 15 dyne/cm2), and E-selectin (3.7-fold vs statc, 2.4-fold vs 15 dyne/cm2). The 1.5 dyne/cm2 group also had increased cytokine/chemokine mRNA expression (> double vs static and 15 dyne/cm2), such as interleukin 1A (IL1A), IL6, IL8, platelet-derived growth factor-B, and monocyte chemotactic protein-1. Pro-coagulant factors, i.e., tissue factor and the plasminogen activator inhibitor-1 mRNA were significantly increased in the 1.5 dyne/cm2 group (2.1-fold vs static, 1.5-fold vs 15 dyne/cm2). COX2 mRNA expression increased in a shear-magnitude-dependent manner.
Our results demonstrate that relatively low shear stress causes the up-regulation of pro-inflammatory gene in HRMECs.
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