Fig. 3. Lipomatous metaplasia in the early chronic phase of MI is unique to hemorrhagic MIs and is observed exclusively at the confluence of iron and lipid remnants.

Serial paraffin sections from an 8-week-old hemorrhagic MI stained with elastin-modified Masson’s trichrome (EMT), H&E, and Prussian Blue (PB) stains from a zone of the peripheral zone of sub-endocardium are presented in panel a (zoomed-in section of panel a (arrow) are presented “in square”/dotted line boxes/rectangles). Individual foam cells were exclusively observed in the peripheral and border zones of hemorrhagic MIs and exclusively co-localized with residual iron deposits. Serial frozen sections from an 8-week-month-old hemorrhagic MI stained with EMT, H&E, Oil-Red-O (ORO), and PB stains are presented in panels b–d. As evident in panel b, foam cells were observed only at the confluence of iron (PB-stained regions) and lipid deposits (ORO regions). In contrast, iron+/lipid− regions (panel c) as well as the iron−/lipid+ (panel d) regions from the same animal did not exhibit LM. Additional examples of LM in the peripheral zone of the midmyocardium and at the border zone of the infarct territories and its relation to iron and foam cells in hemorrhagic animals are shown in Supplementary Fig. 2. For 8-week-old non-hemorrhagic MI scenario, refer to Supplementary Fig. 3. Scale bar in panel a equals 500 µm while in Panels b–d equals 100 µm. The number of samples per timepoint/animal group used is depicted in Supplementary Fig. 1.