TY - JOUR
T1 - Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell‐Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells
AU - Chung, Jihwa
AU - Kim, Kyoung Hwa
AU - Yu, Namhee
AU - An, Shung Hyun
AU - Lee, Sanghyuk
AU - Kwon, Kihwan
N1 - Funding Information:
Funding: This work was supported by the Basic Science Research Program (No. NRF‐ 2017R1A2B2001922) and the Korea Tech Incubator Program for Startup (TIPS) (No. S2832841).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiol-ogy. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)‐derived sEVs (EC‐sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low‐oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. The EC‐sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm2) and atheroprone OSS (±5 dyne/cm2). We explored the miRNA profiles in FSS‐induced EC‐sEVs (LSS-sEVs and OSS‐sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs’ miRNAs‐targeted genes were enriched for endothelial activation such as angio-genesis, cell migration, and vascular inflammation. OSS‐sEVs promoted tube formation, cell migra-tion, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS‐induced EC‐sEVs had the same effects on endothelial mechanotrans-duction signaling as direct stimulation by FSS. In vivo studies showed that LSS‐sEVs reduced the expression of pro‐inflammatory genes, whereas OSS‐sEVs had the opposite effect. Understanding the landscape of EC‐exosomal miRNAs regulated by differential FSS patterns, this research estab-lishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs.
AB - Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiol-ogy. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)‐derived sEVs (EC‐sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low‐oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. The EC‐sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm2) and atheroprone OSS (±5 dyne/cm2). We explored the miRNA profiles in FSS‐induced EC‐sEVs (LSS-sEVs and OSS‐sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs’ miRNAs‐targeted genes were enriched for endothelial activation such as angio-genesis, cell migration, and vascular inflammation. OSS‐sEVs promoted tube formation, cell migra-tion, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS‐induced EC‐sEVs had the same effects on endothelial mechanotrans-duction signaling as direct stimulation by FSS. In vivo studies showed that LSS‐sEVs reduced the expression of pro‐inflammatory genes, whereas OSS‐sEVs had the opposite effect. Understanding the landscape of EC‐exosomal miRNAs regulated by differential FSS patterns, this research estab-lishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs.
KW - Endothelial cell
KW - MicroRNA
KW - Shear stress
KW - Small extracellular vesicles
KW - Systemic network analyses
UR - http://www.scopus.com/inward/record.url?scp=85123369113&partnerID=8YFLogxK
U2 - 10.3390/ijms23031314
DO - 10.3390/ijms23031314
M3 - Article
C2 - 35163238
AN - SCOPUS:85123369113
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 3
M1 - 1314
ER -