Involvement of the antimicrobial peptide LL-37 in human atherosclerosis

Kristina Edfeldt, Birgitta Agerberth, Martin E. Rottenberg, Gudmundur H. Gudmundsson, Xiong Biao Wang, Kaushik Mandal, Qingbo Xu, Zhong Qun Yan

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE-: Antimicrobial peptides are effector molecules of the innate immune system. To understand the function of vascular innate immunity in atherosclerosis, we investigated the role of LL-37, a cathelicidin antimicrobial peptide, in the disease process. METHODS AND RESULTS-: Using real-time polymerase chain reaction, we found a 6-fold increase in human cationic antimicrobial protein 18/LL-37 transcript in human atherosclerotic lesions compared with normal arteries. Immunohistochemical analysis of atherosclerotic plaques showed that LL-37 was expressed mainly by macrophages and some endothelial cells. Western blot demonstrated existence of active LL-37 peptide and abundant proprotein in atheroma specimens. To understand the functional implication of LL-37 production in atherosclerosis, the transcription profile was assessed in endothelial cells treated with LL-37. Our data show that LL-37 induces expression of the adhesion molecule intercellular adhesion molecule-1 and the chemokine monocyte chemoattractant protein 1 in endothelial cells. Intriguingly, Chlamydia pneumoniae withstood the antimicrobial activity of LL-37 in vitro, although inflammatory response was induced on infection. CONCLUSION-: LL-37 is produced in atherosclerotic lesions, where it may function as an immune modulator by activating adhesion molecule and chemokine expression, thus enhancing innate immunity in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1551-1557
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume26
Issue number7
DOIs
StatePublished - Jul 2006

Keywords

  • Antimicrobial peptide
  • Atherosclerosis
  • Immune system
  • Infection
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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