Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1)
| Autor: | Caren E. Petrie Aronin, Meghan M. Nickerson, Edward A. Botchwey, Richard J. Price, Mikell Paige, Kristen A. Wieghaus, Lauren S. Sefcik, Milton L. Brown |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Indoles Materials science Receptors CCR2 Biophysics Neovascularization Physiologic Bioengineering CCL2 Monocytes Article Cell Line Biomaterials Neovascularization Mice Cell Movement In vivo medicine Animals Humans Receptor Microvessel Cell Proliferation Mice Knockout biology Monocyte Cell biology Mice Inbred C57BL medicine.anatomical_structure Integrin alpha M Mechanics of Materials Microvessels Immunology Ceramics and Composites biology.protein Arteriogenesis medicine.symptom |
| Zdroj: | Biomaterials. 29:4698-4708 |
| ISSN: | 0142-9612 |
| Popis: | Phthalimide neovascular factor (PNF1, formerly SC-3-149) is a potent stimulator of proangiogenic signaling pathways in endothelial cells. In this study, we evaluated the in vivo effects of sustained PNF1 release to promote ingrowth and expansion of microvascular networks surrounding biomaterial implants. The dorsal skinfold window chamber was used to evaluate the structural remodeling response of the local microvasculature. PNF1 was released from poly(lactic-co-glycolic acid) (PLAGA) films, and a transport model was utilized to predict PNF1 penetration into the surrounding tissue. PNF1 significantly expanded microvascular networks within a 2mm radius from implants after 3 and 7 days by increasing microvessel length density and lumenal diameter of local arterioles and venules. Staining of histological sections with CD11b showed enhanced recruitment of circulating white blood cells, including monocytes, which are critical for the process of vessel enlargement through arteriogenesis. As PNF1 has been shown to modulate MT1-MMP, a facilitator of CCL2 dependent leukocyte transmigration, aspects of window chamber experiments were repeated in CCR2(-/-) (CCL2 receptor) mouse chimeras to more fully explore the critical nature of monocyte recruitment on the therapeutic benefits of PNF1 function in vivo. |
| Databáze: | OpenAIRE |
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