Author + information
- Ivan Cokic,
- Avinash Kali,
- Hsin-Jung Yang,
- Richard Tang,
- Joseph Francis and
- Rohan Dharmakumar
Background: Iron-laden macrophages (siderophages) are prone to transforming into foam cells. Activated mast cells are known to mediate foam cell formation. Since iron is known to be a potent mast cell activator, we hypothesized that mast cells promote conversion of siderophages into foam cells in hemorrhagic myocardial infarctions (MI).
Methods: Ten dogs were subjected to 3-hr occlusion of the LAD artery, followed by reperfusion, and underwent T2* and LGE CMR on day 7 post-MI. Animals were sacrificed 6 months post-MI at which time the hearts were explanted for histopathological analysis of iron deposits, mast cells, macrophages, phospholipid oxidation products and foam cells.
Results: All dogs exhibited the presence of intramyocardial hemorrhage in acute MI, as evidenced by T2* CMR (Figure 1A & B). Histopathological studies demonstrated both iron and fat deposits within all chronic MIs. Moreover, sparse fat deposits within scars were exclusively colocalized with iron deposits, mast cells, newly recruited MAC387+ macrophages, oxidized phospholipid products (EO6+ regions), CD36+ foam cells, iron induced CD163+ macrophages, as well as the proinflammatory markers (IL-1β, TNF-α and MMP9) (Figure 1C-L).
Conclusions: Our data suggest that fat infiltration within scars of previously hemorrhagic MIs has its origin in mast cell-mediated conversion of siderophages into foam cells. Iron-mast cell-macrophage interaction is a key driver of adverse myocardial remodeling post-MI.
Poster Hall, Hall C
Friday, March 17, 2017, 3:45 p.m.-4:30 p.m.
Session Title: Diabetes and Endothelial Dysfucntion in Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1162-248
- 2017 American College of Cardiology Foundation