Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries

J Am Coll Cardiol. 2018 Aug 28;72(9):1015-1026. doi: 10.1016/j.jacc.2018.06.044.


Background: In the months after acute myocardial infarction (MI), risk for acute atherothrombotic events in nonculprit arteries increases several fold.

Objectives: This study investigated whether sustained proinflammatory and prothrombotic endothelial alterations occur in remote vessels after MI.

Methods: Wild-type mice, atherosclerotic mice with double knockout (DKO) of the low-density lipoprotein receptor and Apobec-1, and DKO mice treated with the Nox-inhibitor apocynin were studied at baseline and at 3 and 21 days after closed-chest MI. Ultrasound molecular imaging of P-selectin, vascular cell adhesion molecule (VCAM)-1, von Willebrand factor (VWF) A1-domain, and platelet GPIbα was performed. Intravital microscopy was used to characterize post-MI leukocyte and platelet recruitment in the remote microcirculation after MI.

Results: Aortic molecular imaging for P-selectin, VCAM-1, VWF-A1, and platelets was increased several-fold (p < 0.01) 3 days post-MI for both wild-type and DKO mice. At 21 days, these changes resolved in wild-type mice but persisted in DKO mice. Signal for platelet adhesion was abolished 1 h after administration of ADAMTS13, which regulates VWF multimerization. In DKO and wild-type mice, apocynin significantly attenuated the post-MI increase for molecular targets, and platelet depletion significantly reduced P-selectin and VCAM-1 signal. On intravital microscopy, MI resulted in remote vessel leukocyte adhesion and platelet string or net complexes. On histology, high-risk inflammatory features in aortic plaque increased in DKO mice 21 days post-MI, which were completely prevented by apocynin.

Conclusions: Acute MI stimulates a spectrum of changes in remote vessels, including up-regulation of endothelial inflammatory adhesion molecules and platelet-endothelial adhesion from endothelial-associated VWF multimers. These remote arterial alterations persist longer in the presence of hyperlipidemia, are associated with accelerated plaque growth and inflammation, and are attenuated by Nox inhibition.

Keywords: adhesion molecules; myocardial infarction; platelets; von Willebrand factor.

Publication types

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

MeSH terms

  • Animals
  • Blood Cell Count
  • Disease Models, Animal
  • Mice
  • Myocardial Infarction / blood*
  • P-Selectin / blood
  • Platelet Activation
  • Vascular Cell Adhesion Molecule-1 / blood
  • von Willebrand Factor / metabolism


  • P-Selectin
  • Vascular Cell Adhesion Molecule-1
  • von Willebrand Factor