Immune responsive resolvin D1 programs myocardial infarction‐induced cardiorenal syndrome in heart failure

Resolvins are innate, immune responsive, bioactive mediators generated after myocardial infarction (MI) to resolve inflammation. The MI‐induced bidirectional interaction between progressive left ventricle (LV) remodeling and kidney dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins limit MI‐induced cardiorenal inflammation is unclear. Thus, to define the role of exogenous resolvin D (RvD)‐1 in post‐MI CRS, we subjected 8‐ to 12‐wk‐old male C57BL/6 mice to coronary artery ligation. RvD1 was injected 3 h after MI. MI mice with no treatment served as MI controls (d 1 and 5). Mice with no surgery served as naive controls. In the injected mice, RvD1 promoted neutrophil (CD11b+/Ly6G+) egress from the infarcted LV, compared with the MI control group at d 5, indicative of neutrophil clearance and thereby resolved inflammation. Further, RvD1‐injected mice showed higher reparative macrophages (F4/80+/Ly6Clow/CD206+) in the infarcted LV than did MI control mice at d 5 after MI. RvD1 suppressed the miRNA storm at d 1 and limited the MI‐induced edematous milieu in a remote area of the LV compared with the MI control at d 5 after MI. Also, RvD1 preserved the nephrin expression that was diffuse in the glomerular membrane at d 5 and 28 in MI controls, indicating renal injury. RvD1 attenuated MI‐induced renal inflammation, decreasing neutrophil gelatinase‐associated lipocalin and proinflammatory cytokines and chemokines in the kidney compared with the MI control. In summary, RvD1 clears MI‐induced inflammation by increasing resolving leukocytes and facilitates renoprotective mechanisms to limit CRS in acute and chronic heart failure.—Halade, G.V., Kain, V., Serhan, C.N. Immune responsive resolvin D1 programsmyocardial infarction‐induced cardiorenal syndrome in heart failure. FASEB J. 32, 3717–3729 (2018). www.fasebj.org