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

Sefcik Anderson, Lauren; Mac Gabhann, F.; Botchwey, E. A.; Wamhoff, B. R.; MacDonald, T. L.; Shin, S. J.; Petrie Aronin, C. E.; Peirce, S. M.; Awojoodu, A. O.; Lynch, K. R.

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

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.

Title	Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth
Creator	Sefcik Anderson, Lauren
	Mac Gabhann, F.
	Botchwey, E. A.
	Wamhoff, B. R.
	MacDonald, T. L.
	Shin, S. J.
	Petrie Aronin, C. E.
	Peirce, S. M.
	Awojoodu, A. O.
	Lynch, K. R.
Publisher	Tissue Engineering Part A
Academic Department	Chemical & Biomolecular Engineering
Division	Engineering
Organization	Lafayette College
Date Issued	March 2011
Date Available	2011-03-18T19:48:25Z
Type	Article
Language	English
Bibliographic 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.
Standard Identifier	DOI 10.1089/ten.tea.2010.0404
Standard Identifier	Handle 10385/826
Permalink	http://hdl.handle.net/10385/826
Rights Statement	In Copyright
Rights Holders	Mary Ann Liebert, Inc.