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

Abstract

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/Ly6C/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 programs myocardial infarction-induced cardiorenal syndrome in heart failure.

Lipoxin and Resolvin Receptors Transducing the Resolution of Inflammation in Cardiovascular Disease

“…Consequently, mice lacking the murine homolog of ALX/FPR2 exhibit an exacerbated inflammatory response following for example mesenteric ( Brancaleone et al, 2013 ) and cerebral ( Vital et al, 2016 ) ischemia and reperfusion. ALX/FPR2 is also upregulated during myocardial ischemia, and its ligands limit myocardial necrosis and inflammation after coronary ligation ( Kain et al, 2015 ; Halade et al, 2018 ). The protective effects of the latter studies are centered on a neutrophil response, both in terms of neutrophils being the major source of LXA 4 production during ischemia and that ALX/FPR2 signaling limits the neutrophil adherence and infiltration into the ischemic area ( Brancaleone et al, 2013 ; Vital et al, 2016 ).…”

Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction

“…A sustained exposure to granule proteins and their oxidation products is ultimately cytotoxic and leads to long-term adverse post-MI LV remodeling [ 189 ]. The conclusion is that NETs and secreted proteins are neither exclusively pro- nor anti-inflammatory mediators, but that their timely resolution is surely crucial for resolving inflammation and inhibiting further damage [ 61 ]. Thus, NETosis and neutrophil degranulation need to be carefully regulated if post-MI wound healing is to proceed in a balanced way.…”

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

“…These are involved at different stages of infarct healing, ultimately leading to scar formation, and harmonize remodeling to preserve cardiac function (9)(10)(11). On-time leukocyte entry failure (delayed "get-in" signal) at the site of injury or prolonged residual time at the site of infarction (delayed "get-out" signal) causes development of nonresolving, uncontrolled chronic inflammation in the cardiac repair program (12)(13)(14)(15).…”