Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Bhatnagar, Aruni

Committee Co-Chair (if applicable)

Spite, Matthew

Committee Member

Conklin, Daniel

Committee Member

Schuschke, Dale

Committee Member

D'Souza, Stanley

Committee Member

Wead, William

Subject

Wound healing; Inflammation--Mediators

Abstract

Wound healing is a highly concerted cellular process that begins with inflammation and proceeds to resolution to revascularize the site of injury. Although inflammation is essential to revascularization during wound healing, it is now recognized that resolution is an active process that is equally important. Other investigations have implicated a beneficial effect of resolving inflammation and promoting resolution in the remission of inflammatory pathologies. Recently investigations have yielded a novel class of ?-3 fatty acid derived lipid mediators, biosynthesized by leukocytes, which are capable of resolving inflammation and promoting resolution. We therefore hypothesized that these leukocyte-derived pro-resolving lipid mediators can promote revascularization to enhance wound healing. In the following studies, we provide evidence supporting this hypothesis: 1) that the ?-3 fatty acid derived pro-resolution lipid mediator Resolvin D2 enhances perfusion recovery of ischemic tissue 2) that inflammatory monocytes, which increase during revascularization, synthesize Resolvin D2 through the 12/15-lipoxygenase pathway 3) and that resolvin D2 does not stimulate angiogenesis, but stimulates arteriogenesis through the promotion of endothelial cell migration. These results suggest that Resolvin D2 can enhance revascularization and may be an effective therapeutic agent.

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