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Heparan sulfate proteoglycan mediates shear stress‐induced endothelial gene expression in mouse embryonic stem cell‐derived cells
Author(s) -
Nikmanesh Maria,
Shi ZhongDong,
Tarbell John M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1043.17
Subject(s) - embryonic stem cell , glycocalyx , cd31 , microbiology and biotechnology , endothelial stem cell , heparan sulfate , mechanotransduction , stem cell , chemistry , biology , cell , gene , in vitro , biochemistry
The goal of this study is to evaluate the role of wall shear stress (SS) on the development of vascular endothelial cells from mouse embryonic stem cells (mESCs) differentiated in vitro . The CD31 + /CD45 − cells have been derived from embryonic stem cells (ESCs) and these derivatives can be further maturated into endothelial like cells by SS. However, the underlying mechanisms of SS in this process have yet to be investigated. In this work, the role of glycocalyx in shear stress mechanotransduction will be investigated. Results ESC‐derived CD31 + /CD45 − cells were subjected to SS (5 dyn/cm 2 ) for 8 hours with or without heparinase III (Hep) treatment. Hep is an enzyme which specifically digests cell surface heparan sulfate proteoglycan (HSPG). We observed that shear stress increased gene expression of the vascular endothelial cell‐specific markers (vWF, VE‐cadherin, PECAM‐1) and tight junction molecules (ZO‐1, OCLD, CLDN5). Shear stress also increased vasoactive genes (eNOS, COX‐2) expression, while it decreased vasoconstricive gene (ET‐1) expression. After removal of HSPG, the SS‐induced expression of vWF, VE‐cadherin, ZO‐1, eNOS, and COX‐2 were abolished, suggesting that SS‐induced expression of these genes is dependent on HSPG. Conclusion These findings indicate that HSPG plays as a mechanosensor in mediating shear stress‐induced EC maturation from ESC‐derived cells. Supported by: NIH/NHLBI 1 RO1 HL086543 ‐01 and State of New York Department of Health (NYSTEM)