Nitric oxide regulation of platelet function

NOflux
Activated platelets adhere to and aggregate on type I fibrillar collagen on NO releasing polymer surfaces at 500 1/s. Annexin V (red) labels PS positive platelets and anti-CD41 (green) labels all platelets. A control and two NO fluxes are shown. Scale bar = 25 µm.

Nitric oxide (NO) is an important regular of vascular health and disease. Among it many functions is the inhibition of platelet activation. NO is secreted from the endothelial cells that line blood vessels in a shear stress dependent manner. When a blood vessel is injured, endothelial cells can be damaged causing the exposure of the subendothelial matrix, which contains adhesive proteins for platelets (e.g. collagen) and procoagulant tissue factor. It is unknown how the NO expressed by endothelial cells adjacent to an injury regulate clot growth. We have developed computational models of NO transport that suggest that NO is contained only within the 2-5 micrometer red blood cell free region near the vessel wall, and that its concentration in this near wall region is weakly dependent on shear rate, but strongly dependent on wall flux. In collaboration with Mellisa Reynolds at Colorado State University, we have integrated a NO releasing polymer into our microfluidic vascular injury models. The figure above shows how the NO wall flux can reduce platelet aggregation on collagen. We have also used this system to determine the relative role of the soluble guanylyl cylase pathway on NO-mediated platelet inhibition.

Relevant Publications

J.L. Sylman, D.T. Artzer, K. Rana, K.B. Neeves. A vascular injury model using focal heat-induced activation of endothelial cells. Integrative Biology, 15 (2015): 801-814. PMID:26087748

J.L. Sylman, S.M. Lantvit, M.M. Reynolds, K.B. Neeves. The relative role of soluble guanylyl cylase dependent and independent pathways in nitric oxide inhibition of platelet aggregation under flow. Cellular and Molecular Bioengineering, 7 (2014): 421-431.

J.L. Sylman, S.M. Lantvit, M.C. VeDepo, M.M. Reynolds, K.B. Neeves. Transport limitations of nitric oxide inhibition of platelet aggregation under flow. Annals of Biomedical Engineering, 41 (2013): 2193-2205. PMID: 23563992