Neutrophil degranulation and myocardial infarction

Abstract

Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Graphical abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP‐8, MMP‐9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP‐8); Matrix metalloproteinase 9 (MMP‐9).

Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase

“…This is the first study of its kind to demonstrate that neutrophils and neutrophil elastase are involved in Dox-induced cardiotoxicity. In pre-clinical models in rats, NE inhibitors ablated the ischemia-induced myocardial damage and coronary endothelial dysfunction ( 36 ). Furthermore in clinical trials, NE inhibitors have been used to treat cystic fibrosis and chronic obstructive pulmonary disease and have been found to be safe and well tolerated and effective in curbing the excess inflammatory response ( 37 , 38 ).…”

P2X7 accelerate tissue fibrosis via metalloproteinase 8‐dependent macrophage infiltration in a murine model of unilateral ureteral obstruction

“…P2X 7 R activation has been shown to regulate MMP9 expression indirectly via IL‐1β signaling in atherosclerotic vessels (Lombardi et al., 2017), but there is no apparent connection between P2X 7 and MMP8. However, P2X 7 activation has been demonstrated to increase the intracellular Ca 2+ concentration in neutrophils, and neutrophils are known to store MMP8 in tertiary granules release by degranulation (for review, see Zhang et al., 2022). Thus, P2X 7 activation is likely to increase the release of MMP8, and the observed increase in interstitial MMP8 could originate from activation from invading neutrophils.…”

Severe, but not moderate asthmatics share blood transcriptomic changes with post-traumatic stress disorder and depression

“…P-value = 5.6E-6) [94], and myocardial infarction and neutrophil degranulation (Adj. P-value = 2.6E-4) [95]. Looking at the top 5 for genes enriched in healthy subjects compared to MDD and severe asthma we identified many matches associated with ribosomal regulation, and to a lesser extent immune function and anemia (Adj.…”