Abstract
Unresolved inflammation is a major contributor to heart failure following myocardial infarction (MI). Pro-resolving lipid mediators, including resolvins (e.g. RvD1), are biosynthesized endogenously. The role of RvD1 in resolving post-MI inflammation has not been addressed. Here, we tested whether liposomal RvD1 (Lipo-RvD1) or Pure-RvD1 limit left ventricle (LV) and splenic remodeling by resolving post-MI inflammation. 8 to 12 week old male C57BL/6 mice were subjected to coronary artery ligation and Lipo-RvD1 or pure-RvD1 (3ug/kg/day) was injected 3 hour post-MI for day (d)1 or until d5. No-MI mice and MI mice were treated with saline as controls. RvD1 injected groups showed improved fractional shortening post-MI (p<0.05) and preserved transient changes in splenic reservoir compared to MI control. RvD1 groups showed early exit of neutrophils from LV and spleen compared to MI-controlat d5 post-MI. RvD1 groups showed reduced macrophage density compared to MI-control with reduced ccr5 and cxcl5 levels at d5 post-MI (p<0.05). Increased transcripts of mrc-1, arg-1 and Ym-1; p<0.05 suggests macrophage-mediated clearance of necrotic cells in RvD1 groups. RvD1-injected mice exhibited reduced post-MI fibrosis with reduced collagen deposition. Pro-fibrotic genes (colla1, coll2a1 and Tnc; p<0.05) reduction indicated a stabilization of extracellular matrix at d5 in RvD1 groups. RvD1-mediated pro-resolving actions were also supported by increased 5-lipoxygenase (LOX) and decreased 12-LOX levels at d5 post-MI. In summary, these results indicated that liposomal and pure-RvD1 show potential pro-resolving activity to remit uncontrolled inflammation and delay heart failure.
Published Version
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