Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction

High levels of lactate are positively associated with the prognosis and mortality in patients with heart attack. Endothelial-to-mesenchymal transition (EndoMT) plays an important role in cardiac fibrosis. Here, we report that lactate exerts a previously unknown function that increases cardiac fibrosis and exacerbates cardiac dysfunction by promoting EndoMT following myocardial infarction (MI). Treatment of endothelial cells with lactate disrupts endothelial cell function and induces mesenchymal-like function following hypoxia by activating the TGF-β/Smad2 pathway. Mechanistically, lactate induces an association between CBP/p300 and Snail1, leading to lactylation of Snail1, a TGF-β transcription factor, through…

• AH
  American Heart Association

  Award: 916710
• NI
  National Institutes of Health

  Awards: GM083016, HL071837, GM119197, C06RR0306551