Selectin-targeting glycosaminoglycan-peptide conjugate limits neutrophil-mediated cardiac reperfusion injury

Cardiovasc Res. 2022 Jan 7;118(1):267-281. doi: 10.1093/cvr/cvaa312.


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.

Methods and results: 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.

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

Keywords: Endothelial cell dysfunction; Fibrosis; Glycocalyx; Inflammation; Myocardial infarction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • E-Selectin / metabolism*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Fibrosis
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Neutrophil Activation / drug effects*
  • Neutrophil Infiltration / drug effects*
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Platelet Activation / drug effects
  • Signal Transduction


  • Anti-Inflammatory Agents
  • E-Selectin