• miR-199a-3p directly targets the 3'UTR of Vldlr, suppressing its expression and promoting cardiomyocyte proliferation.
• Vldlr acts as a functional target of miR-199a-3p, as its overexpression blunts the pro-proliferative effect.
• The miR-199a-3p-Vldlr axis regulates RB1 phosphorylation at S807/811, which is essential for cardiomyocyte proliferation.
• This study identifies a novel miR-199a-3p-Vldlr-RB1 axis, offering potential therapeutic targets for cardiac regeneration.