Post-ischemic Myocardial Inflammatory Response: A Complex and Dynamic Process Susceptible to Immunomodulatory Therapies

Abstract

Following acute occlusion of a coronary artery causing myocardial ischemia and implementing first-line treatment involving rapid reperfusion, a dynamic and balanced inflammatory response is initiated to repair and remove damaged cells. Paradoxically, restoration of myocardial blood flow exacerbates cell damage as a result of myocardial ischemia–reperfusion (MI-R) injury, which eventually provokes accelerated apoptosis. In the end, the infarct size still corresponds to the subsequent risk of developing heart failure. Therefore, true understanding of the mechanisms regarding MI-R injury, and its contribution to cell damage and cell death, are of the utmost importance in the search for successful therapeutic interventions to finally prevent the onset of heart failure. This review focuses on the role of innate immunity, chemokines, cytokines, and inflammatory cells in all three overlapping phases following experimental, mainly murine, MI-R injury known as the inflammatory, reparative, and maturation phase. It provides a complete state-of-the-art overview including most current research of all post-ischemic processes and phases and additionally summarizes the use of immunomodulatory therapies translated into clinical practice.

Innate Lymphoid Cells and Myocardial Infarction

“…Though not direct evidence for ILCs in MIRI, several groups (22,(41)(42)(43) have reported roles for ILCs in IRI and ILC-related cytokines in MIRI, suggesting that ILCs can play important roles in MIRI, with ILC2s being the most promising candidate.…”

“…24-72 hours after MIRI, expression of pro-inflammatory cytokines decreased significantly, and levels of fibrotic mediators such as TGF-b and IL-10 showed a continuous and rapid increase, reflecting suppression of acute inflammation and transition to cardiac repair and proliferation (41,42). Recently, Pluijmert et al (43) summarized the multifactorial and dynamic process of the inflammatory response in MIRI, including TNF-a, IL-4, IL-13, IL-10 and TGF-b. These results suggested that cytokines, especially those related to ILCs, play important roles in MIRI (22).…”

Macrophage Migration Inhibitory Factor Levels Predict No-reflow in ST-segment Elevation Myocardial Infarction.

“…MIF playing an essential role in ischemic preconditioning-induced myocardial protection may ameliorate altered cardiac function and adverse cardiac remodeling through various ways, including suppression of ischemia-induced salvage kinase pathway, CD74/ AMP-activated protein kinase signal system, and its components [47,48]. In addition, MIF exerts protective effects by suppression of myocardial healing and maintenance of cardiac function through promoting CXCR2 in resident cells [49]. Eventually, MIF can down-regulate the level of apoptosis of injured cardiac myocytes and circulating mature and progenitor endothelial cells, thereby preventing them from revascularization damage [49].…”

“…In addition, MIF exerts protective effects by suppression of myocardial healing and maintenance of cardiac function through promoting CXCR2 in resident cells [49]. Eventually, MIF can down-regulate the level of apoptosis of injured cardiac myocytes and circulating mature and progenitor endothelial cells, thereby preventing them from revascularization damage [49]. However, these data allow us to explain the plausible molecular mechanisms by which pre-PCI MIF influenced coronary blood flow recovery and myocardial function maintenance.…”

The Role of Immune Cell Types in Ischemic Heart Disease Progression: A Systematic Review

“…The common causative mechanism of IHD is the accumulation of emboli-commonly atherosclerotic plaques-in the coronary arteries [3], which restricts blood vessel diameters [4]. Resultantly, the blood oxygenation and blood supply to target organs are significantly reduced, affecting downstream biological processes and metabolic balance [3][4][5]. Clinical symptoms of IHD include shortness of breath; constrictions of the chest, neck, and jaw area; and cold sensations, which are further exacerbated by physical and emotional stress [2,6].…”