Fig. 7
From: Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases
Novel HPTMs: dual roles in cardiac repair and fibrosis. When MI occurs, monocytes undergo metabolic reprogramming, leading to dysregulated glycolysis and consequently increased lactate production. The generated lactate is transported into monocytes via MCT1 and accumulates intracellularly, providing the substrate for histone la. Upon histone la, specific reparative genes such as Lrg1, Vegf-a, and IL-10 are activated and expressed. The expression of these genes modulates the dual anti-inflammatory and pro-angiogenic activities of monocytes, ultimately promoting cardiac repair. In additional, the activation of PAD4 is triggered by an increase in calcium ion concentration, leading to histone cit and the formation of NETs. NETs are composed of DNA, histones, and antimicrobial proteins and are released into the extracellular space. These NETs promote inflammatory responses, damage cardiomyocytes and endothelial cells, and interact with platelets, promoting the release of TGFβ, which in turn promotes myofibroblast fibrosis. NET formation and fibrosis are increased, whereas mice lacking PAD4 exhibit reduced fibrosis and maintain good cardiac function
