HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction

Abstract

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.

High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases

“…HMGB1 stimulates the recruitment and stimulation of macrophages, promoting angiogenesis through FGF-2, TGFβ1, and VEGF secretion [ 91 ]. In the heart, it was demonstrated that HMGB1 induces angiogenesis after injury by upregulating VEGF expression, but further studies are needed to understand how HMGB1 induces VEGF release [ 92 ].…”

“…The recent findings indicate that endogenous HMGB1 can be useful as a diagnostic and prognostic biomarker in human cardiac disorders [ 95 ]. Several studies have indicated that exogenous HMGB1 can have a beneficial effect on cardiac regeneration [ 92 ].…”

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

“…Monocytes transformed into cellular macrophages are considered to be the predominant producers of various pro-inammatory cytokines, namely, IL-1b, IL-6, IGF-1, TGF-b, TNF-a and VEGF, involved in both normal wound healing and diabetic healing processes. 41,42 The detailed pathophysiology of DFU is explained in Fig. 2.…”

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

“…However, recent studies have shown another aspect of HMGB1: its important role in promoting tissue repair and reconstruction. It has been found in many studies that the HMGB1 signal pathway can promote the repair function in the diseases such as palate trauma in the oral cavity, lung epithelial injury and acute myocardial infarction [ 76 , 77 , 78 ]. Additionally, the studies of cerebral hemorrhage also confirmed that HMGB1 promotes angiogenesis and nerve regeneration in the late stage of cerebral hemorrhage [ 79 , 80 , 81 ].…”