View : 37 Download: 0
Fluid shear stress regulates the expression of Lectin-like oxidized low density lipoprotein receptor-1 via KLF2-AP-1 pathway depending on its intensity and pattern in endothelial cells
- Fluid shear stress regulates the expression of Lectin-like oxidized low density lipoprotein receptor-1 via KLF2-AP-1 pathway depending on its intensity and pattern in endothelial cells
- Lee, Ji Yoon; Chung, Jihwa; Kim, Kyoung Hwa; An, Shung Hyun; Kim, Minsuk; Park, Junbeom; Kwon, Kihwan
- Ewha Authors
- 권기환; 김민석; 박준범
- SCOPUS Author ID
- 권기환; 김민석; 박준범
- Issue Date
- Journal Title
- ATHEROSCLEROSIS vol. 270, pp. 76 - 88
- Fluid shear stress; Vascular endothelial cells; LOX-1; Mechanosensory complex; Kruppel-like factor 2; Activator protein-1
- ELSEVIER IRELAND LTD
- SCI; SCIE; SCOPUS
- Document Type
- Background and aims: Vascular endothelial cells (ECs) are exposed to fluid shear stress (FSS), which modulates vascular pathophysiology. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is crucial in endothelial dysfunction and atherosclerosis. We elucidated the mechanism regulating LOX-1 expression in ECs by FSS. Methods: Human umbilical vein endothelial cells were exposed to laminar shear stress (LSS) of indicated intensities using a unidirectional steady flow, or to oscillatory shear stress (OSS) using a bidirectional disturbed flow. In vivo studies were performed in a mouse model of partial carotid ligation and human pulmonary artery sections. Results: Within ECs, OSS upregulated LOX-1 expression, while LSS (20 dyne/cm(2)) downregulated it. We confirmed that OSS-induced LOX-1 expression was suppressed when the mechanotransduction was inhibited by knockdown of the mechanosensory complex. In addition, we demonstrated that Kruppellike factor 2 (KLF2) has an inhibitory role on OSS-induced LOX-1 expression. Next, we determined that activator protein-1 (AP-1) was the key transcription factor inducing LOX-1 expression by OSS, which was inhibited by KLF2 overexpression. To explore whether the intensity of LSS affects LOX-1 expression, we tested three different intensities (20, 60, and 120 dyne/cm(2)) of LSS. We observed higher LOX-1 expression with high shear stresses of 120 dyne/cm(2) compared to 20 and 60 dyne/cm(2), with OSS-like KLF2-AP-1 signaling patterns. Furthermore, ECs within disturbed flow regions showed upregulated LOX-1 expression in vivo. Conclusions: We concluded that LOX-1 expression on ECs is regulated via FSS depending on its intensity as well as pattern. Furthermore, this is mediated through the KLF2-AP1 pathway of mechanotransduction. (C) 2018 Elsevier B.V. All rights reserved.
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.