Key result
Nur77 deficiency aggravated cardiac dysfunction and cardiac fibrosis 30 days after myocardial infarction by enhancing endothelial-to-mesenchymal transition.
Why the study?
Endothelial-to-mesenchymal transition contributes to post-MI cardiac fibrosis, but the role of the orphan nuclear receptor Nur77 in this process remained unknown.
Does Nur77 regulate endothelial-to-mesenchymal transition and cardiac fibrosis after myocardial infarction?
Does Nur77 regulate endothelial-to-mesenchymal transition and cardiac fibrosis after myocardial infarction?
Nur77 protects against cardiac fibrosis and remodeling after myocardial infarction by inhibiting endothelial-to-mesenchymal transition via the NF-κB pathway.
Nur77 deficiency promotes post-MI fibrosis via EndMT; hypothesis-generating for targeted therapies pending translational validation.
Cardiac fibrosis is a reparative process after myocardial infarction (MI), which leads to cardiac remodeling and finally heart failure. Endothelial-to-mesenchymal transition (EndMT) is induced after MI and contributes to cardiac fibrosis after MI. Orphan nuclear receptor Nur77 is a key regulator of inflammation, angiogenesis, proliferation, and apoptosis in vascular endothelial cells. Here, we investigated the role of orphan nuclear receptor Nur77 in EndMT and cardiac fibrosis after MI. Cardiac fibrosis was induced through MI by ligation of the left anterior descending coronary artery. We demonstrated that Nur77 knockout aggravated cardiac dysfunction and cardiac fibrosis 30 days after MI. Moreover, Nur77 deficiency resulted in enhanced EndMT as shown by increased expression of FSP-1, SM22α, Snail, and decreased expression of PECAM-1 and eNOS compared with wild-type mice after MI. Then, we found overexpression Nur77 in human coronary artery endothelial cells significantly inhibited interleukin 1β and transforming growth factor β2-induced EndMT, as shown by a reduced transition to a fibroblast-like phenotype and preserved angiogenesis potential. Mechanistically, we demonstrated that Nur77 downregulated EndMT by inhibiting the nuclear factor-κB-dependent pathway. In conclusion, Nur77 is involved in cardiac fibrosis by inhibiting EndMT and may be a promising target for therapy of cardiac fibrosis after MI.
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Chen et al. (2020) studied Cardiac fibrosis after myocardial infarction. Nur77 deficiency vs. Wild-type was evaluated on Cardiac dysfunction and cardiac fibrosis. Nur77 deficiency aggravated cardiac dysfunction and cardiac fibrosis 30 days after myocardial infarction by enhancing endothelial-to-mesenchymal transition.
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