Details

Autor(en) / Beteiligte

• Ding, Zufeng
• Liu, Shijie
• Deng, Xiaoyan
• Fan, Yubo
• Wang, Xianwei
• Mehta, Jawahar L

Titel

Hemodynamic shear stress modulates endothelial cell autophagy: Role of LOX-1

Ist Teil von

• International journal of cardiology, 2015-04, Vol.184, p.86-95

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Objectives Shear stress, autophagy and LOX-1 are important players in atherogenesis. Direct impact of shear stress on autophagy development in endothelial cells and role of LOX-1 therein are undelineated. Methods and results A parallel-plate flow chamber was used to vary shear stress (3 to 30 dyn/cm2 ), and determine autophagy in endothelial cells. We observed that low shear stress (3 dyn/cm2 ) enhanced autophagy (expression of LC3-II) 2–3 fold, and increasing shear stress (15 to 30 dyn/cm2 ) resulted in a gradual decline. Autophagy increased when cells were treated with an inflammatory stimulus lipopolysaccharide (LPS). LOX-1 expression paralleled autophagy development. The in vitro observations were confirmed in the in vivo setting by studying autophagy (LC3-II and Beclin-1) and LOX-1 expression in wild-type mice given LPS. Expression of both autophagy and LOX-1 was most pronounced in aorto-iliac bifurcation region where shear stress is lower compared with aortic arch, thoracic aorta and iliac artery. To define the role of LOX-1 in the development of autophagy, we studied LOX-1 knockout mice. These mice despite LPS administration exhibited less autophagy (vs. wild-type mice). Role of LOX-1 in the regulation of autophagy was further established with LOX-1 inhibition (siRNA transfection and use of antibody) or overexpression (cDNA transfection), which showed that LOX-1 knockdown reduced while LOX-1 overexpression enhanced LC3-II expression in endothelial cells. Conclusions These observations suggest that low shear stress is a powerful regulator on autophagy, particularly in state of inflammation, and LOX-1 plays an important role in shear stress induced autophagy.