The study shows that the natural peptide LL‑37 can push blood‑vessel lining cells to turn into scar‑like cells, a process linked to plaque buildup in arteries. This suggests that raising LL‑37 levels might worsen heart disease, but the research doesn’t give any clear way to use the peptide for health benefits.

Endothelial-to-mesenchymal transition (EndMT) is a process that causes endothelial cells (ECs) to lose their EC characteristics and transform into mesenchymal cells. Accumulating studies suggest that EndMT is induced in atherosclerotic plaques and contributes to the pathogenesis of atherosclerosis. LL-37 is a multifaceted peptide with antimicrobial and immunomodulatory actions. Interestingly, LL-37 is localized in atherosclerotic plaques, suggesting an association between EndMT and LL-37 in atherosclerosis. Thus, we examined the EndMT-inducing activity of LL-37 using human umbilical vein ECs. LL-37 decreased EC markers but increased mesenchymal cell markers in the cells. LL-37 decreased the vascular network formation of the cells but increased the cell migration, a characteristic function of mesenchymal cells. Finally, the LL-37-induced EndMT was inhibited by Akt and nuclear factor-kappa B (NF-κB) inhibitors, suggesting that LL-37 induces EndMT by activating Akt and NF-κB. These observations speculate a role of LL-37 in the pathogenesis of atherosclerosis as an EndMT inducer.