Arachidonic Acid (AA) Metabolism, Systemic Inflammation and Cardiovascular Disease (CVD) in Patients with Renal Failure

Patients with renal failure have a significant risk of CVD. AA metabolites are important in the regulation of inflammation and have been implicated in the pathogenesis of CVD. We explored the relationship between AA metabolism and CVD in this high risk population. Samples from 59 renal failure patients were obtained at the time of transplantation. Serum lipid metabolites involving pathways of cytochrome P450, soluble epoxy hydrolase, cyclooxygenase and lipoxygenase were analyzed by HPLC and inflammatory markers involving innate (neopterin) and adaptive (CD40 ligand) immunity were assessed by ELISA. A segment of inferior epigastric artery was assessed for CVD (intima proliferation and vascular calcifications). The frequency of CVD and vascular calcifications was 51% and 54%, respectively. Patients with vascular calcifications had elevated 14,15‐ and 11.12‐EET (1.8‐fold, p<0.05 and 3.7‐fold, p =0.09). Increased neopterin correlated with high 11,12‐EET and 6‐keto‐PGF1α. Elevated CD40 ligand correlated with 11,12‐EET, 14,15‐EET and 6‐keto‐PGF1α (table 1), as well as with intima proliferation (p=0.05) and vascular calcifications (p<0.05). The association of serum AA metabolites with systemic inflammation and CVD is consistent with a role of altered AA metabolism in the pathogenesis of CVD. This study was funded by an American Heart Association Grant.