Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases

Abstract

Chronic heart diseases have in common an unresolved inflammatory status. In atherosclerosis, myocarditis, myocardial infarction, or atrial fibrillation, mounting evidence suggests that unresolved inflammation contributes to the chronicity, aggravation, and morbidity of the disease. Following cardiac injury or infection, acute inflammation is a normal and required process to repair damaged tissues or eliminate pathogens and promote restoration of normal functions and structures. However, if acute inflammation is not followed by resolution, a chronic and deleterious inflammatory status may occur, characterized by the persistence of inflammatory biomarkers, promoting aggravation of myocardial pathogenesis, abnormal structural remodeling, development of cardiac fibrosis, and loss of function. Although traditional antiinflammatory strategies, including the use of COX-inhibitors, to inhibit the production of inflammation promotors failed to promote homeostasis, mounting evidence suggests that activation of specific endogenous autacoids may promote resolution and perpetuate cardioprotective effects. The recent discovery of the active mechanism of resolution suggests that proresolving signals and cellular processes may help to terminate inflammation and combat the development of its chronic profile in cardiac diseases. This review discussed (I) the preclinical and clinical evidence of inflammation-resolution in cardiac disorders including atrial fibrillation; (II) how and why many traditional antiinflammatory treatments failed to prevent or cure cardiac inflammation and fibrosis; and (III) whether new therapeutic strategies may interact with the resolution machinery to have cardioprotective effects. Graphical abstract RvD D-series resolving, RvE E-series resolving, LXA4 lipoxin A4, MaR1 maresin-1

Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway

“…MaR1 was also found to inhibit acute lung-injury-induced neutrophil infiltration and adhesion in mice and downregulate the generation of inflammatory mediators [ 18 ]. Studies have demonstrated that MaR1 is effective in preventing atherosclerosis and could be used as a new potential therapeutic strategy to eliminate arterial inflammation [ 19 ]. Nevertheless, the role of MaR1 in septic rats and its regulation on microglia in septic rats remains to be explored.…”

Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review

“…If untreated and unresolved, the inflammatory status may lead to cardiomyocytes-, fibroblasts- and pro-inflammatory-(M1)-macrophage-induced production of inflammation-related compounds such as IL-6, TNFα, or NF-kB [ 121 , 122 , 123 , 124 ]. In the heart, such inflammatory signaling coupled with evident poisoning-induced oxidative stress has been demonstrated to promote abnormal calcium-Ca 2+ -handling, RyR2 dysfunction, delayed or shortened repolarization, triggered action potential, shortened effective refractory periods, and atrial fibrosis [ 15 , 109 , 125 , 126 ].…”