Endothelial Cells Overexpressing Interleukin-8 (IL8) Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
Background—Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and RB receptors prevents inflammatory responses and promotes structural recovery of arteries following endoluminal injury.
Methods and Results—Young adult male rats received balloon injury of the right carotid artery and were transfused i.v. with ECs (total 1.5x106 cells at 1, 3, and 5 hrs post injury) transduced with adenoviral vectors carry IL8RA, IL8RB, IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited pro-inflammatory mediators expression significantly (by 60-85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day post injury, as well as stimulating a 2-fold increase in re-endothelialization at 14 days post injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days post injury.
Conclusions—ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
- Received November 8, 2011.
- Accepted February 15, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited