Inflammation revisited: inflammation versus resolution of inflammation following myocardial infarction

Abstract

Myocardial infarction (MI) is the main cause for the progression of the left ventricle towards congestive heart failure. The optimal healing after MI requires timely induction and resolution of inflammation. Primarily, there have been a number of strategies applied to inhibit the post-MI inflammation but approaches that focus on the resolution of inflammation have sparsely been used in the treatment of heart failure. The early attempts to inhibit post-MI inflammation resulted in adverse outcomes that were realized in heart failure trials. We provide here an overview on the cyclooxygenase (COX)- and lipoxygenase (LOX)-derived lipid mediators that are either impairing or resolving the post-MI inflammation. With the evolution of lipidomics there has been emerging novel bioactive-specialized lipid mediators that promise to resolve chronic inflammation rather than promoting inhibition. The current review is focused on post-MI immune cells kinetics and the unexplored array of lipid mediators that are coordinated by COX and LOX. Thus, an emphasis on COX and LOX poses key questions and potential for the development of novel targets in the heart failure treatment strategy. This updated dynamic approach aims to fuse basic pre-clinical discoveries and translational bioactive lipid-based resolvin discoveries that could be potentially used in the clinic for the treatment of heart failure.

Cytoprotective activated protein C averts Nlrp3 inflammasome–induced ischemia-reperfusion injury via mTORC1 inhibition

“…However, myocardial IRI is strongly associated with inflammation, 37 and hence, we speculated that inflammasome activation might be the leading pathomechanism. To gain insights into the temporal pattern of inflammasome and apoptosis activation after myocardial IRI, we conducted kinetic studies.…”

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

“…(10,41) A deregulated immune reaction can lead to changes in ventricular shape, size, and function and can, thus, induce the development of heart failure syndrome. (4,15) Therefore, it would be desirable to develop new therapeutic strategies to modulate immune response and improve healing after MI (1).…”

“…Classically, macrophages and lymphocytes are the leading infiltrating cells in the infarcted myocardium, and these cells show a functional and phenotypic plasticity during the resolution phase of inflammation (15,27). M1 macrophages that produce high amounts of proinflammatory cytokines mediate the initial inflammatory response, and M2 macrophages that produce mainly anti-inflammatory cytokines involved in repair functions dominate the healing phase (36).…”

“…M1 macrophages that produce high amounts of proinflammatory cytokines mediate the initial inflammatory response, and M2 macrophages that produce mainly anti-inflammatory cytokines involved in repair functions dominate the healing phase (36). Subpopulations of T lymphocytes with proinflammatory and anti-inflammatory profiles have been found in the myocardium after MI (15,27). Likewise, the adaptive immune system plays a central role in the pathogenesis of ventricular remodeling after myocardial ischemic injury (33,36).…”

Innate Immune Mechanisms in Myocardial Infarction - An Update

“…An exacerbated inflammatory phase amplifies the ischemic myocardial damage, leading to additional loss of systolic function. On the other hand, an extended reparatory phase might lead to excessive myocardial fibrosis and diastolic dysfunction (3).…”