Project 1 is an ongoing project of HL 42550 which, historically, utilized a chronic model of ischemia and reperfusion in the dog to characterize the robust inflammatory reaction ensuring upon reperfusion of the infarcted myocardium. The unique features of this model including cannulation of the cardiac lymph duct which allowed collection of extracellular fluid providing an in vivo based reagent for in vitro cell biological experiments. We also utilized tissue samples calibrated for degree of ischemia to localize and quantitate mRNA and protein. In vitro models using isolated cells were developed to incorporate the features observed in vivo and better delineate mechanisms. Utilizing these strategies, we proposed a model of the cellular and molecular mechanisms associated with leukocyte chemotaxis, post-reperfusion myocardial injury, and a generation of inflammatory cascade of growth factors and cytokines that we proposes to be important in the facilitation of tissue repair induced by reperfusion. This paradox of that ordinarily protect healthy tissue from inflammatory injury and the cellular and molecular roles of inflammatory cells and inflammatory based mediators in tissue repair and cytoprotection. This is and has been the long-term goal of this program project grant; each of the Projects relates to these issues. Project 1 will expand on three observations made in the current grant period that examine the cellular and molecular mechanisms and potential roles of reperfusion dependent events. 1) Transition of neutrophils infiltrating the reperfused infarct to the major early source of fibrogenic and angiogenic stimuli. 2) Early attraction of mast cell precursors and increase in mast cell number in the reperfused infarct and its role in ventricular repair. 3) Rapid reperfusion-dependent induction of important chemokines in the venular endothelium and its downstream consequences with regard to leukocyte trafficking and angiogenesis.
| Mann, Douglas L (2014) Colchicine and the failing heart: a ""FINER"" anti-inflammatory agent? JACC Heart Fail 2:138-40 |
| Burns, Alan R; Phillips, Sharon C; Sokoya, Elke M (2012) Pannexin protein expression in the rat middle cerebral artery. J Vasc Res 49:101-10 |
| Mann, Douglas L (2012) Sphingosine 1-phosphate as a therapeutic target in heart failure: more questions than answers. Circulation 125:2692-4 |
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| Wu, Huaizhu; Gower, R Michael; Wang, Hong et al. (2009) Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119:2708-17 |
| Liu, Xiuping; Zuo, Yumei; Zhang, Weina et al. (2009) Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells. J Huazhong Univ Sci Technolog Med Sci 29:527-34 |
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