INTRODUCTION: Patients with diabetes are at high risk of developing cardiovascular complications, including CAD and stroke, due to chronic inflammation leading to the build-up of atherosclerotic plaque in the arterial wall. Recent insights into the use of pro-resolving molecules, such as Lipoxin A4 (LXA4), has highlighted the novel therapeutic potential of Lipoxins against atherosclerosis. Here, we investigated the effectiveness of number of LXA4 mimetics in attenuating diabetes-associated atherosclerosis (DAA). 

AIM: The aim of this study was to investigate the therapeutic potential of LXA4 and two LXA4 mimetics against DAA in diabetic ApoE-/- mice 

METHODS: ApoE-/- mice were rendered diabetic by five-daily intraperitoneal (IP) injections of streptozotocin (55mg/kg); control mice received citrate buffer. LXA4 and LXA4 mimetics were administered twice weekly for 10-weeks via IP injection in control and diabetic mice. At end-point, mice were culled and aortae collected and analysed for plaque deposition, gene expression, immunohistochemistry and histology.

RESULTS: Preliminary results show that diabetic animals had increased blood glucose and serum glycated haemoglobin, as well as significantly elevated aortic plaque deposition(~5-fold) compared to control mice. Administration of LXA4 and mimetics significantly attenuated atherosclerotic plaque area (~70%). We also found that the mimetics significantly attenuated the TNFα induced inflammatory markers and cytokines (MCP1,IL1β,IL6,ICAM1,VCAM1,~50%)  in primary endothelial cells and the PDGF mediated induction of the proliferation marker, PCNA(~70%) in primary aortic smooth muscle cells. 

CONCLUSION: To date, our findings reveal novel pro-resolving effects of LXA4 mimetics against inflammation induced-atherosclerosis, reversing inflammatory processes and plaque deposition. These results support our hypothesis that LXs can be used as a novel approach for the treatment of DAA.

04 - THERAPEUTIC ACTIONS OF PRO-RESOLVING LIPOXIN A4 MIMETICS AGAINST ATHEROSCLEROSIS