Controlling Vascular Wall Healing

Healing_1The treatment of lower extremity vascular disease through the use of balloon or laser angioplasty, stenting, or atherectomy remains limited by a significant incidence of restenosis. Thus, new approaches that target thrombotic and inflammatory events, which contribute to restenosis and delayed vessel wall healing are required. We postulate that thrombin and purinergic dependant pathways can be inhibited by antibody mediated targeting of thrombomodulin, CD39, and CD73 to the site of vessel wall injury. Moreover, we hypothesize that nanoparticles produced from recombinant protein polymers will provide an effective mechanism for site-specific delivery of resolvins and their metabolic precursors that will further accelerate both the resolution of the inflammatory response and the reconstitution a functionally intact endothelium. As such, we anticipate that by abrogating early inflammatory and thrombotic responses, intimal hyperplasia will be limited after catheter-based interventions.

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Krishnamurthy VR, Dougherty A, Haller CA, Chaikof EL. Total synthesis and bioactivity of 18R-hydroxy eicosapentaenoic acid. J Organic Chemistry 2011; 76: 5433-5437

Topcic D, Kim W, Holien JK, Jia F, Armstrong PC, Hohmann JD, Straub A, Krippner G, Haller CA, Domeij H, Hagemeyer CE, Parker MW, Chaikof EL*, Peter KP*. An activation-specific platelet inhibitor that can be turned on/off by medically employed hypothermia. Arteriosclerosis Thromb Vasc Biol 2011; 31:2015-23.

Kim W, Xiao J, Chaikof EL. Recombinant amphiphilic protein micelles for drug delivery. Langmuir 2011; 27: 14329-14334

Kim W, Brady C, Chaikof EL. Amphiphilic protein micelles for targeted in vivo imaging. In press Acta Biomaterialia 2012; 8:2476-2482.