Laminar shear stress promotes mitochondrial homeostasis in endothelial cells. Issue 6 (15th January 2018)

• Record Type: Journal Article
• Authors: Wu, Li‐Hong; Chang, Hao‐Chun; Ting, Pei‐Ching; Wang, Danny L.
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 6(2018:Jun.)
• Page Start: 5058
• Page End: 5069
• Publication Date: 2018-01-15
• Subjects: endothelial cells -- laminar shear stress -- mitochondrial dynamics -- mitochondrial homeostasis -- TNFα; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26375
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Vascular endothelial cells (ECs) are constantly subjected to flow‐induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm 2 ) generated by a parallel‐plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long‐ and short‐ OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission‐controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα‐induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation‐induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity. Abstract : Laminar Shear Stress Promotes Mitochondrial Homeostasis in Endothelial Cells.