Cardiac Regeneration from Activated Epicardium
Figure 5
Post-ischemic mesenchyme formation.
Snai1 mRNA is present from three days onwards in the subepicardial mesenchyme of the apex and LV covering the infarct (A), and border zone (B). qPCR analysis (C) showed that Snai1 is already induced at one day post-MI and remains high up to two weeks post-MI, after which it gradually returns to control levels. Its close relative Snai2 shows a similar activation pattern as Snai1, with the exception that Snai2 is already detected in the healthy control heart. Within the border zone (D) and infarcted area (E) the matricellular proteins Follistatin-like1 (E,H) and Periostin (F,I) are expressed at high levels in the non-myocardial cells (cf D,G). In control hearts, α-SMA is present in the smooth muscle layer of the coronaries (J). At one and two weeks post-MI α-SMA is detected in the subepicardial mesenchyme and in mesenchymal cells located in the myocardium adjacent to the epicardium overlaying the infarct (K,L). At one and two weeks post-MI α-SMA-postive subepicardial mesenchyme is also found in the atria (M). P-Smad is only found in a small minority of subepicardial mesenchymal cells (arrow) directly flanking myocardial cells and adjacent to the infarct (N). Whereas P-Erk is detected in the nucleus of a subset of epicardial cells in controls and after an infarction, as well as in the cytoplasm and nucleus of an extensive subset of the subepicardial mesenchyme (O–Q). The bar is 100 µm.