Description:
Resolvins are innate immune responsive lipid mediators produced after myocardial infarction (MI) to resolve inflammation. MI‐induced bidirectional interaction between progressive left ventricle remodeling and kidney dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins limits MI‐induced cardiorenal dysfunction is unclear. Thus, to define the role of resolvin D1 (RvD1) in post‐MI CRS, we tested the hypothesis using 8 to 12 weeks old male C57BL/6 mice that were subjected to coronary artery ligation surgery. RvD1 (3ug/kg/day) was injected 3 hour post‐MI for day (d)1 or continued till d5. No‐MI naïve and saline‐injected MI mice were used as controls. RvD1‐injected group promoted neutrophils (CD11b+/Ly6G+; 2.0±0.3%) egress from infarcted LV compared with MI‐control group (4.2±2.0%) at d5 post‐MI. Further, RvD1 injected mice showed higher reparative macrophages (F4/80+/Ly6Clow/CD206+; 20.0±1.0%) phenotype in the infarcted LV compared with MI‐control group (14.4±2.1%) at d5 post‐MI measured by flow cytometry. MI‐induced LV remote hypertrophy was limited in RvD1‐injected mice compared with MI‐control mice confirmed using wheat germ agglutinin staining. Post‐MI nephrin expression was diffused to glomerular membrane at d5 in MI‐control mice indicating renal injury impacting kidney glomerulus structure but to a lesser extent in RvD1‐injected mice validated using immunofluorescence staining. Administration of RvD1 attenuated MI‐induced renal inflammation decreasing neutrophil gelatinase‐associated lipocalin (2.0±0.1 fold p<0.05) gene and protein expression in the kidney at d1 post‐MI (2.2±0.1 fold; p<0.5) and d5 compared to MI‐control. In conclusion, RvD1 not only clears MI‐induced inflammation by increasing resolving leukocytes but also is renoprotective in nature in heart failure pathology.Support or Funding InformationHL132989 and AT006704 to GVH