Abstract P130: Specialized Pro-resolving Mediator, Lipoxin A4, Attenuates Age-dependent Vascular Damage

Abstract

Chronic, low-grade inflammation that develops with advanced age is known as inflammaging. This phenomenon is associated with large artery stiffness in age-dependent hypertension. Specialized pro-resolving mediators (SPMs), including Lipoxin A4 (LXA4) and Resolvin D1 (RD1), are derived from essential fatty acids, and they act as immunoresolvents to reduce inflammation and increase the clearance of pathogens and dying cells. However, LXA4, but not RD1, acts on formyl peptide receptor 2, which is known to modulate actin filaments and resolve inflammation. Therefore, we hypothesized that Specialized pro-resolving mediators, would restore mechanical stress and distensibility in aorta from older rats. To test this hypothesis, thoracic aortas from male Wistar rats (3 and 6 months old) were cut into 2 mm rings and incubated in the presence or absence of RD1 or LXA4; both 10 nM for 24 hours. Stress-strain curves were calculated via Tissue Puller (560TP-II, DMT). The aortic rings from 6-month-old rats presented with increased stress when compared to aortas of the 3-month-old (Maximal stress: 2749 ± 190 mN/mm 2 vs 4207 ± 242 mN/mm 2 , respectively; p=0.0015). Interestingly, LXA4 reduced stress in aorta from 6-month-old rats (Maximal stress: 2514 ± 552 mN/mm 2 , p=0.0282). No changes were observed in aorta from 3-month-old rats after LXA4 treatment. Resolvin D1 did not change vascular mechanics in aorta from 3- or 6-month-old rats. Overall, these data suggest that even modest advances in age are related with changes in vascular mechanics of large arteries and LXA4 via FPR2 can decrease inflammaging-related vascular stiffness.