Mechanotransduction of the endothelial glycocalyx mediates nitric oxide production through activation of TRP channels.
The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the vascular endothelium, serving critical functions in the mechanotransduction of blood flow-induced forces. One of the most important protective functions of the ESG is to mediate the production of nitric oxide (NO) in response to blood flow. However, the detailed mechanism underlying ESG's mechanotransduction of the production of NO has not been completely identified. Herein, using the cultured rat brain microvascular endothelial cells (bEnd.3) as a model system, we have implemented a combined atomic force and fluorescence microscopy approach to show that the ESG senses and transduces vertical mechanical stretch to produce NO. This rapid NO production is dependent on the presence of both heparan sulfate (HS) and hyaluronic acid (HA) in ESG, as the removal of HS and/or HA leads to a significant decrease in NO production. Moreover, the production of NO is dependent on the intake of Ca2+via endothelial transient receptor potential (TRP) channels. Together, our results demonstrate the molecular mechanism of rapid production of NO in response to vertical mechanical stretch.
Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, Pennsylvania.
Matthew A
MA
Dragovich
Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
Daniel
D
Chester
Department of Biomedical Engineering, The City College of the City University of New York, New York, New York; and.
Bingmei M
BM
Fu
Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
Chenyu
C
Wu
Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, Pennsylvania.
Yan
Y
Xu
Department of Medicine and Pharmacology, New York Medical College, Valhalla, New York.
Michael S
MS
Goligorsky
Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, Pennsylvania; xiz310@lehigh.edu.|Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
X Frank
XF
Zhang
D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology*; D019276:Glycocalyx / Q000378:metabolism* / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D009569:Nitric Oxide; D050051:Transient Receptor Potential Channels
TRP channels; atomic force microscopy; endothelial cells; glycocalyx; mechanotransduction