The cathelicidin peptide LL-37, traditionally known as an antimicrobial agent, plays multiple roles in heart disease including regulating atherosclerosis, thrombosis, inflammation, and cardiac hypertrophy.
4 cardiovascular roles identifiedLL-37 — originally known only as an antimicrobial peptide — has been found to regulate atherosclerosis, thrombosis, inflammatory responses, and cardiac hypertrophy, revealing it as a multifunctional cardiovascular modulator.
What the researchers found
LL-37, the only human cathelicidin antimicrobial peptide, has been found to regulate multiple cardiovascular processes beyond its traditional antimicrobial role:
- Atherosclerosis regulation — LL-37 influences plaque formation and stability in blood vessels
- Thrombosis modulation — the peptide affects blood clot formation
- Inflammatory response control — LL-37 modulates cardiac inflammatory pathways
- Cardiac hypertrophy regulation — the peptide influences heart muscle thickening
Engineered LL-37-related peptides have been developed and shown to regulate disease progression in experimental models, demonstrating potential for clinical application in cardiovascular disease.
Why it matters
Heart disease remains the leading cause of death worldwide, and current treatments primarily target individual risk factors (blood pressure, cholesterol, blood sugar). Discovering that an endogenous peptide like LL-37 simultaneously influences multiple cardiovascular pathways — from plaque formation to blood clotting to heart muscle remodeling — suggests a new therapeutic paradigm. Peptide-based therapies modeled on LL-37 could potentially address multiple aspects of heart disease simultaneously.
How the study worked
This is a comprehensive review article that synthesizes published research on LL-37's roles in cardiovascular disease. The authors surveyed studies covering LL-37's involvement in atherosclerosis, thrombosis, inflammation, cardiac hypertrophy, and related pathways, as well as research on engineered LL-37-derived peptides.
What this study cannot tell us
As a review article, this paper synthesizes existing evidence rather than generating new data. The cardiovascular roles of LL-37 have been demonstrated primarily in preclinical models, with limited human clinical evidence. The review does not include a systematic search methodology or meta-analysis. Whether LL-37's diverse cardiovascular effects are beneficial or harmful may depend on context, dosing, and disease stage — complexities that are not fully resolved.
How to read the evidence
This is a narrative review published in a high-impact pharmacology journal, synthesizing preclinical and mechanistic research. While it provides a comprehensive overview, most of the evidence comes from animal models and in vitro studies, with limited direct human cardiovascular data for LL-37.
When this study was published
Published in 2024, this is a very recent review capturing the latest understanding of LL-37's cardiovascular roles. Research on antimicrobial peptides in cardiovascular disease is a rapidly growing field.
The bigger picture
LL-37 is part of the cathelicidin family of antimicrobial peptides, which represent an ancient branch of innate immunity. The discovery that these infection-fighting peptides also regulate cardiovascular biology blurs the traditional boundary between antimicrobial defense and cardiovascular health. This aligns with the broader recognition that chronic inflammation — the domain of innate immune peptides — is a central driver of heart disease. LL-37 may represent a molecular link between infection, inflammation, and cardiovascular damage.
Questions still open
- Could LL-37 levels serve as a biomarker for cardiovascular disease risk or progression?
- Do engineered LL-37-derived peptides retain antimicrobial properties while gaining cardiovascular benefits, enabling dual-purpose therapeutics?
- Is LL-37's role in heart disease primarily protective or harmful, and does this change across different disease stages?
Common questions
What is LL-37 and why is it normally important?
Could LL-37 be used as a heart disease treatment?
Read the original research
Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease.
Pharmacological research, 210, 107529
Citation
Miao, Shuo; Liu, Houde; Yang, Qingyu; Zhang, Yaping; Chen, Tao; Chen, Shuai; Mao, Xin; Zhang, Qingsong. (2024). Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease.. Pharmacological research, 210, 107529. https://doi.org/10.1016/j.phrs.2024.107529