resolvin-d1 and Aortic-Aneurysm--Abdominal

Topics: Animals; Aortic Aneurysm, Abdominal; Disease Models, Animal; Docosahexaenoic Acids; Mice

Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis.. The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P < .001). On postoperative day 3, the RvD1-treated group showed decreased levels of NETosis markers citrullinated histone H3 (P = .04) and neutrophil elastase (P = .002) compared with the elastase group. Among important cytokines involved in AAA formation, interleukin (IL) 1β was downregulated (P = .02) whereas IL-10, a protective cytokine, was upregulated (P = .01) in the RvD1-treated group. Active matrix metalloproteinase 2 also decreased in the RvD1-treated group (P = .03). The RvD1-treated group in the Ang II AAA model, a second model, demonstrated reduced AAA diameter compared with the Ang II control group on day 28 (P < .046). The RvD1-treated group showed decreased levels of citrullinated histone H3 on day 3 (P = .002). Cytokines interferon γ, IL-1β, C-X-C motif chemokine ligand 10, monocyte chemotactic protein 1, and regulated on activation, normal T cell expressed and secreted (RANTES) were all decreased on day 28 (P < .05).. RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.

Topics: Animals; Anti-Inflammatory Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Citrullination; Cytokines; Disease Models, Animal; Docosahexaenoic Acids; Extracellular Traps; Histones; Inflammation Mediators; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Mice, Knockout, ApoE; Neutrophils; Pancreatic Elastase; Vascular Remodeling