Published online before print April 27, 2006, doi: 10.1161/01.ATV.0000223901.08459.57
© 2006 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Involvement of the Antimicrobial Peptide LL-37 in Human Atherosclerosis
From the Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital (K.E., Z.-q.Y.), the Immunological Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital (X.-B.W.), the Department of Medical Biochemistry and Biophysics (B.A.), the Microbiology and Tumorbiology Centre (M.E.R.), Karolinska Institute, Stockholm, Sweden; the Institute of Biology, University of Iceland, Reykjavik, Iceland (G.H.G.); the Department of Cardiothoracic Surgery, St. George’s Hospital and Medical School, London, UK (K.M., Q.X.); and College of Pharmacy, Dalian Medical University, China (Z.-q.Y.)
Correspondence to Zhonq-qun Yan, Cardiovascular Research Unit, Center for Molecular Medicine, CMM L8:03, Karolinska University Hospital, 171 76 Stockholm, Sweden. E-mail Zhong-qun.Yan{at}cmm.ki.se
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.
To understand the function of vascular innate immunity in atherosclerosis, we investigated the role of the antimicrobial cathelicidin peptide LL-37 in atherosclerosis. We found that 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.
Key Words: atherosclerosis • antimicrobial peptide • immune system • inflammation • infection
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