Aims: One of the hallmarks of myocardial infarction (MI) is excessive inflammation. During an inflammatory insult, damaged endothelial cells shed their glycocalyx, a carbohydrate-rich layer on the cell surface which provides a regulatory interface to immune cell adhesion. Selectin-mediated neutrophilia occurs as a result of endothelial injury and inflammation. We recently designed a novel selectin-targeting glycocalyx mimetic (termed DS-IkL) capable of binding inflamed endothelial cells. This study examines the capacity of DS-IkL to limit neutrophil binding and platelet activation on inflamed endothelial cells, as well as the cardioprotective effects of DS-IkL after acute myocardial infarction. 

In vitro, DS-IkL diminished neutrophil interactions with both recombinant selectin and inflamed endothelial cells, and limited platelet activation on inflamed endothelial cells. Our data demonstrated that DS-IkL localized to regions of vascular inflammation in vivo after 45 min of left anterior descending coronary artery ligation-induced MI. Further, findings from this study show DS-IkL treatment had short- and long-term cardioprotective effects after ischaemia/reperfusion of the left anterior descending coronary artery. Mice treated with DS-IkL immediately after ischaemia/reperfusion and 24 h later exhibited reduced neutrophil extravasation, macrophage accumulation, fibroblast and endothelial cell proliferation, and fibrosis compared to saline controls. 

Our findings suggest that DS-IkL has great therapeutic potential after MI by limiting reperfusion injury induced by the immune response.

DS-IkL_Set1 and DS-IkL_Set2: Collected Jan 2018 – Jan 2020

Flow Cytometry Raw Data Files (zipped folders). Requires a flow cytometry analysis software (e.g., FlowJo) to open. Raw data from the flow cytometry data shown in Figure 7. Data represents the expression of endothelial markers, fibroblast markers, neutrophil markers, macrophage/monocyte markers, and proliferation markers in non-myocyte cells in the hearts of I/R and sham mice. 

IR_compiled_data_as_of_2020.09.05.pzfx and PMN_inhibition_compiled.pzfx: Collected Jan 2018-Aug 2020

Compiled experimental data from figures 1-7. Requires GraphPad PRISM to open. IR compiled data contains all data from the in vivo study. PMN inhibition compiled contains data from in vitro experiments.