Abstract 122: Supervised Exercise Therapy for Claudication Modulates Global Profiles of Plasma Lipid Mediators

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Background: Lipid mediators are complex molecules that demonstrate an association to inflammatory states including atherosclerotic vascular disease. Peripheral artery disease (PAD) is an atherosclerotic disease of the distal aorta and lower extremity arteries. Supervised walking therapy (SWT) is the mainstay of treatment for PAD and is hypothesized to improve claudication by suppressing inflammatory activation. Objectives: We sought to examine how lipid mediators were impacted by treadmill testing in PAD, and to identify lipid mediators that were altered by SWT. Methods: Plasma samples were collected before and after Gardner treadmill testing (GTT) in individuals with PAD; participants underwent 12 weeks of SWT and were retested. Lipid mediators were isolated using Ostro Sample Preparation Plates (Waters; Milford, MA) and quantified by UPLC-MS/MS. Results: Thirty-six participants had complete sets of plasma for analysis. The median age was 67 years (IQR: 62 - 71); there were 55 men (73%) and the median ABI was 0.64 (IQR: 0.55 - 0.76). The median peak walking time prior to SWT was 7.4 min (IQR: 4.8 - 10.3 min), which increased to 11.9 min (IQR: 8.4 - 17.1) after SWT (p < 10 -4 ). Discriminant analysis showed clear separation of pre- and post- GTT and pre- and post- SWT samples based on global lipid profiles (Figure 1). Cluster analysis demonstrated 13 distinct clusters of lipid mediators; those clusters containing carbon and arachidonic acid epoxides, and vicinal diols were significantly (FDR <5%) impacted by the interaction between SWT and GTT. Conclusions: Lipid mediator profiles manifested unique response patterns to treadmill testing and were modified by supervised walking therapy. These data suggest that lipid mediators play an active role in the biology underlying improvements in lower extremity symptoms associated with SWT and may offer a novel target for therapeutic manipulation.