Abstract 12784: Targeted Delivery of Endothelial Cells by Overexpressing Interleukin-8 Receptors Inhibits Neointimal Responses to Vascular Injury: Novel Mechanism of Vasoprotection
Introduction: Interleukin receptors IL8RA and IL8RB on neurophil membranes bind to IL8 with high affinity and play a critical role in neutrophil recruitment (e.g. adhesion and trans-endothelial migration) to sites of infection and/or inflammation. We have previously shown that rat carotid artery expresses high levels of IL8 within 2 hrs of endoluminal injury. The current study tested the novel hypothesis that administration of IL8RA- and/or IL8RB-infected endothelial cells (ECs) can accelerate the adhesion of ECs to the injured surface and reendothelialization, suppressing neointima formation in balloon injured carotid arteries.
Methods: 12 wk old male Sprague-Dawley rats received balloon injury of the right carotid artery and were divided into four subgroups: Group 1 received i.v. vehicle; Group 2 received i.v. ECs infected with pAd-IL8RA (total 1.5×106 cells at 1, 3, and 5 hrs post injury); Group 3 received ECs infected with pAd-IL8RB; and Group 4 received ECs infected with both pAd-IL8RA and pAd-IL8RB. Rats were sacrificed 4 wks post-injury. Cross-sectional intima-to-media (I/M) ratios of injured carotid arteries were determined.
Results: Comparisons of I/M ratios for rats received ECs that overexpress IL8RA and/or IL8RB are shown in the figure (results are means±SEM, * p<0.05 vs control). IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced I/M ratios by 80%, 74%, and 95%, respectively.
Conclusions: These provocative findings indicate that ECs with overexppression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to the injured tissues. The targeted delivery of ECs to site of arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
- © 2010 by American Heart Association, Inc.