Published online before print October 16, 2003, doi: 10.1161/01.RES.0000101744.47866.D5
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Submitted on June 11, 2003
Revised on October 6, 2003
Accepted on October 6, 2003
Heparan Sulfate Proteoglycan Is a Mechanosensor on Endothelial Cells
Jeffry A. Florian ;
From the Biomolecular Transport Dynamics Laboratory (J.A.F., J.R.K., K.A., Z.P., J.M.T.), Departments of Chemical Engineering and Bioengineering, The Pennsylvania State University, University Park, Pa; and the Department of Anesthesiology and Critical Care Medicine (R.O.D.), The Johns Hopkins University School of Medicine, Baltimore, Md.
* To whom correspondence should be addressed. E-mail: tarbell{at}ccny.cuny.edu.
The objective of this study was to test whether a glycosaminoglycan component of the surface glycocalyx layer is a fluid shear stress sensor on endothelial cells (ECs). Because enhanced nitric oxide (NO) production in response to fluid shear stress is a characteristic and physiologically important response of ECs, we evaluated NOx (NO2- and NO3-) production in response to fluid shear stress after enzymatic removal of heparan sulfate, the dominant glycosaminoglycan of the EC glycocalyx, from cultured ECs. The significant NOx production induced by steady shear stress (20 dyne/cm2) was inhibited completely by pretreatment with 15 mU/mL heparinase III (E.C.2.2.2.8) for 2 hours. Oscillatory shear stress (10±15 dyne/cm2) induced an even greater NOx production than steady shear stress that was completely inhibited by pretreatment with heparinase III. Addition of bradykinin (BK) induced significant NOx production that was not inhibited by heparinase pretreatment, demonstrating that the cells were still able to produce abundant NO after heparinase treatment. Fluorescent imaging with a heparan sulfate antibody revealed that heparinase III treatments removed a substantial fraction of the heparan sulfate bound to the surfaces of ECs. In summary, these experiments demonstrate that a heparan sulfate component of the EC glycocalyx participates in mechanosensing that mediates NO production in response to shear stress. The full text of this article is available online at http://www.circresaha.org.
Key words: shear stress • endothelial cells • heparan sulfate • nitric oxide • glycocalyx
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