Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth

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Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth

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dc.contributor.author Sefcik Anderson, Lauren
dc.contributor.author Petrie Aronin, C. E.
dc.contributor.author Awojoodu, A. O.
dc.contributor.author Shin, S. J.
dc.contributor.author Mac Gabhann, F.
dc.contributor.author MacDonald, T. L.
dc.contributor.author Wamhoff, B. R.
dc.contributor.author Lynch, K. R.
dc.contributor.author Peirce, S. M.
dc.contributor.author Botchwey, E. A.
dc.date.accessioned 2011-03-18T19:48:25Z
dc.date.available 2011-03-18T19:48:25Z
dc.date.issued 2011-03
dc.identifier.citation Sefcik Anderson, L., et al. (2011). "Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth." Tissue Engineering Part A 17 (5-6): 617-629. en_US
dc.identifier.uri http://hdl.handle.net/10385/826
dc.description.abstract Proper spatial and temporal regulation of microvascular remodeling is critical to the formation of functional vascular networks, spanning the various arterial, venous, capillary, and collateral vessel systems. Recently, our group has demonstrated that sustained release of sphingosine 1-phosphate (S1P) from biodegradable polymers promotes microvascular network growth and arteriolar expansion. In this study, we employed S1P receptor-specific compounds to activate and antagonize different combinations of S1P receptors to elucidate those receptors most critical for promotion of pharmacologically induced microvascular network growth. We show that S1P(1) and S1P(3) receptors act synergistically to enhance functional network formation via increased functional length density, arteriolar diameter expansion, and increased vascular branching in the dorsal skinfold window chamber model. FTY720, a potent activator of S1P(1) and S1P(3), promoted a 107% and 153% increase in length density 3 and 7 days after implantation, respectively. It also increased arteriolar diameters by 60% and 85% 3 and 7 days after implantation. FTY720-stimulated branching in venules significantly more than unloaded poly(D, L-lactic-co-glycolic acid). When implanted on the mouse spinotrapezius muscle, FTY720 stimulated an arteriogenic response characterized by increased tortuosity and collateralization of branching microvascular networks. Our results demonstrate the effectiveness of S1P(1) and S1P(3) receptor-selective agonists (such as FTY720) in promoting microvascular growth for tissue engineering applications. en_US
dc.publisher Tissue Engineering Part A en_US
dc.title Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth en_US
dc.type Article en_US
dc.identifier.doi 10.1089/ten.tea.2010.0404

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