Fig. 3.

Transient phenotypes after myocardial infarction. A The emergance of innate immune reactions favors an inflammatory-induced phenotype which has been described to occur based on increased pro-inflammatory signaling (TNFα, IL-1β, IL-6). Also levels of TGF-β which can origin from multiple sources are associated with this phenotype. Endothelial cells show increased expression of hematopoietic marker CD45 and major histocompatibility complex (MHC) class II molecules. Whether this phenotype is cleared or leads to a chronic inflamed endothelium is debated. B Endothelial metabolic changes after myocardial infarction. Repression of FOXO1 leads to induction of MYC, which initiates a switch from fatty acid transport to glycolytic signaling. This induction is transient and reverts when normoxic conditions are restored. C Mesenchymal activation induces proliferation and clonal expansion. Hypoxia, inflammation and a glycolytic metabolism with increased TGF-β levels induce mesenchymal marker genes, such as Snai1, Fn1 or Col1a2. Mesenchymal activation has been shown to induce clonal expansion in endothelial cells, leading to neovascularization. Upon loss stimulating TGF-β levels, endothelial cells revert back to a naïve phenotype.