Fig. 6

The role of novel HPTMs and related molecular markers in progression and prognosis of various cancer types in the human body. In the context of MI, monocytes first undergo metabolic reprogramming toward glycolysis, becoming dysregulated and committing to increased lactate production. The lactate is then taken up by MCT1 into monocytes, where it accumulates within the cell as a substrate for histone la, leading to histone la-mediated activation and expression of reparative genes including Lrg1, Vegf-a, and IL-10. These effects of monocyte gene induction enable monocytes to exert dual anti-inflammatory and proangiogenic activities, enhancing cardiac repair. Moreover, an increase in calcium ion concentration is the stimulus for PAD4 activation, which brings citrullinated histones, forming NETs. NETs are composed of DNA, histones, and antimicrobial proteins and are released to the extracellular space. These NETs elicit proinflammatory responses, myocardium- and endothelium-damaging effects, and interaction with platelets to elicit TGFβ release that may propagate a myofibroblast-driven fibrotic response. Indeed, NET formation and fibrosis are enhanced in the context of MI, and such responses are absent in mice deficient in PAD4, which have less fibrosis and a favorable outcome in terms of cardiac function