Deciphering HEArt-liVEr commuNication in nonalcohoLic fattY liver disease – HEAVENLY

Nonalcoholic fatty liver disease (NAFLD) is a major public health issue and an independent risk factor for myocardial infarction (MI) in epidemiological studies. Post-MI cardiac repair conditions patient outcome. Extracellular vesicles (EVs) are vectors of information between organs, found more abundantly in the plasma of NAFLD patients. EVs are implicated in MI. Based on our preliminary data showing that NAFLD directly impairs post-MI cardiac repair in mice without usual CV risk factors, and that circulating EVs from NAFLD patients are enriched in liver proteins, we hypothesize that NAFLD impairs post-MI cardiac repair via liver-derived EVs. By combining our complementary expertise, we will: 1/ delineate the consequences of each stage of NAFLD on post-MI cardiac repair using 3 complementary NAFLD models; and 2/ identify mechanisms underlying liver-heart communication in NAFLD and MI, using hypothesis-based and unbiased approaches.