LL-37 promotes atherosclerosis by inducing blood vessel cells to transform into scar-forming cells | Research

The takeaway

The antimicrobial peptide LL-37 induces endothelial-to-mesenchymal transition in vascular endothelial cells through Akt and NF-κB activation, potentially contributing to atherosclerotic plaque formation.

LL-37 drives EndMT
The antimicrobial peptide LL-37, found in atherosclerotic plaques, induces blood vessel cells to transform into scar-forming cells—a new mechanism for cardiovascular disease

What the researchers found

LL-37: ↓EC markers, ↑mesenchymal markers. ↓Vascular network formation. ↑Cell migration. Mechanism: Akt + NF-κB activation. Blocked by Akt and NF-κB inhibitors. LL-37 localized in atherosclerotic plaques.

Why it matters

EndMT contributes significantly to atherosclerotic plaque formation. Finding that LL-37—an innate immune peptide—drives this process links antimicrobial defense to cardiovascular disease pathogenesis.

How the study worked

In vitro: HUVEC treated with LL-37. EC/mesenchymal marker expression. Network formation assay. Migration assay. Akt and NF-κB pathway inhibitor studies.

What this study cannot tell us

In vitro HUVEC model. LL-37 concentrations may not reflect in vivo plaque levels. EndMT is one of many atherosclerosis mechanisms. Causation in human atherosclerosis not established.

How to read the evidence

In vitro mechanistic study with pathway inhibitor validation. Good mechanism but limited clinical context.

When this study was published

Published in 2025.

The bigger picture

This adds to LL-37's complex dual nature: beneficial for infection defense but potentially harmful in chronic inflammatory conditions like atherosclerosis and psoriasis. The peptide's role depends entirely on context.

Questions still open

Could blocking LL-37 in plaques reduce atherosclerosis progression?
Do patients with high LL-37 levels have worse cardiovascular outcomes?
Is LL-37-induced EndMT reversible?

Common questions

Can an immune defense peptide cause heart disease?

This study shows LL-37—normally a beneficial antimicrobial peptide—can transform blood vessel cells into scar-forming cells (EndMT) when present at high levels in atherosclerotic plaques. This dual nature illustrates how immune defense molecules can become harmful in chronic inflammatory settings.

What is endothelial-to-mesenchymal transition?

EndMT is when blood vessel lining cells (endothelial cells) lose their identity and become mesenchymal cells that produce scar tissue. This contributes to atherosclerotic plaque buildup and vascular stiffening. LL-37 triggers this transition through Akt and NF-κB signaling pathways.

Read the original research

Human cathelicidin peptide LL-37 induces endothelial-to-mesenchymal transition.

Bioscience, biotechnology, and biochemistry, 89(10), 1464-1473

View on PubMed ↗Publisher’s paper ↗

Citation

Suzuki, Kaori; Ohkuma, Mari; Nagaoka, Isao. (2025). Human cathelicidin peptide LL-37 induces endothelial-to-mesenchymal transition.. Bioscience, biotechnology, and biochemistry, 89(10), 1464-1473. https://doi.org/10.1093/bbb/zbaf112