The pericardium promotes cardiac repair and remodelling post-myocardial infarction

Mylonas, K. J.; Jackson-Jones, L. H.; Andrews, J. P. M.; Magalhaes, M. S.; Meloni, M.; Joshi, N. V.; Allen, J. E.; Newby, D. E.; Dweck, M. R.; Gray, G. A.; Benezech, C. A.

doi:10.1101/771154

bioRxiv · 10.1101/771154

The pericardium promotes cardiac repair and remodelling post-myocardial infarction

Mylonas, K. J.·Jackson-Jones, L. H.·Andrews, J. P. M.·Magalhaes, M. S.·Meloni, M.·Joshi, N. V.·Allen, J. E.·Newby, D. E.·Dweck, M. R.·Gray, G. A.·Benezech, C. A.

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Abstract

The pericardium is widely recognised for its lubricating and bio-mechanical properties. It also contains fat-associated lymphoid clusters (FALCs) and its immune functions have been widely overlooked. Here we aimed to assess the inflammatory activity of the pericardium in patients who suffered a recent myocardial infarction (MI) and to determine its importance for repair and remodelling in a murine MI model induced by coronary artery ligation (CAL). By comparing 18F-fluorodeoxyglucose (FDG) activity in the pericardium of patients with stable coronary artery disease and patients who had a recent MI, we demonstrate that MI is associated with increased pericardial inflammation. We confirm in mice, that pericardial FALCs undergo a major expansion following CAL. We show that despite similar initial injury, removal of the pericardium prior to MI disrupted subsequent repair, resulting in 50% mortality due to cardiac rupture, while all mice with intact pericardia survived. Removal of the pericardium also led to decreased staining for Ym1, a marker of reparative macrophages and adverse cardiac fibrosis within the infarct area. Together, this work indicates a crucial role for the pericardium in regulating inflammation, macrophage polarisation and tissue remodelling in the heart following MI.

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Mylonas, K. J., Jackson-Jones, L. H., Andrews, J. P. M., Magalhaes, M. S., Meloni, M., Joshi, N. V., Allen, J. E., Newby, D. E., Dweck, M. R., Gray, G. A., Benezech, C. A.. 2019-09-18. The pericardium promotes cardiac repair and remodelling post-myocardial infarction. https://doi.org/10.1101/771154

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