Abstract 467: Nitric Oxide-Mediated Regulation of the Adiponectin-Adiponectin Receptor Pathway Following Arterial Injury
Objectives Nitric oxide (NO) has been shown to limit the development of neointimal hyperplasia; however, little is known about its effects on the adventitia. Adiponectin is a molecule that originates from periadventitial adipose tissue and has been shown to negatively regulate neointimal growth. Thus, we hypothesize that removal of periadventitial fat from the arterial wall will negatively impact the ability of NO to inhibit the development of neointimal hyperplasia following injury.
Methods The carotid artery injury model was performed on 11-week-old Sprague Dawley rats. Animal models underwent either removal of all periadventitial fat from the artery at the time of surgery (absent) or no disturbance of the periadventitial fat (present). Treatment groups included control, injury, and injury + NO (PROLI/NO, 10mg). Arteries were harvested at 2 weeks. Morphometric analysis was performed using ImageJ software. Immunofluorescent staining was performed for the adiponectin receptor (AR) and assessed using blinded grading (scale 0-4).
Results Morphometric analysis revealed a 29% increase in neointima development in the absent vs. present group (p<0.001). With the application of NO, there was a greater decrease in intima area in the absent than the present group (93% vs. 77%, p<0.001). The results were similar for media area (50% vs. 37%, p<0.001) and the intima/media area ratio (86% vs. 65%, p<0.001). While AR staining showed no significant difference in the media or adventitia with the application of NO in the present group, AR staining was significantly increased in both the media (57%, p=0.009) and adventitia (37%, p<0.05) with the application of NO in the absent group.
Conclusions Removal of the source of periadventitial adiponectin resulted in more neointimal hyperplasia following arterial injury, but a paradoxical NO-mediated increase in AR levels and corresponding responsiveness to NO therapy. These data suggest that AR expression is upregulated in the absence of adiponectin by NO. Further studies that identify the mechanism by which NO may regulate adiponectin may provide a novel therapeutic target to prevent neointimal hyperplasia.
- © 2013 by American Heart Association, Inc.