Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study

Abstract

Background: Death of smooth muscle cells in the atherosclerotic plaques makes the plaques more prone to rupture, which can initiate an acute ischemic event. The development of atherosclerosis includes the migration of immune cells e.g. monocytes/macrophages and T lymphocytes into the lesions. Immune cells can release antimicrobial peptides. One of these, human cathelicidin antimicrobial peptide hCAP-18, is cleaved by proteinase 3 generating a 4.5 kDa C-terminal fragment named LL-37, which has been shown to be cytotoxic. The aim of the study was to explore a potential role of LL-37 in the pathophysiology of atherosclerosis.

Acute ST-Segment Elevation Myocardial Infarction is Associated with Decreased Human Antimicrobial Peptide LL-37 and Increased Human Neutrophil Peptide-1 to 3 in Plasma

“…LL-37 has been found in infiltrating macrophages and in some endothelial cells (ECs) in atherosclerotic lesions 14,15) . It may induce ICAM-1 and MCP-1 expression in cultured HUVECs 14) , and induce apoptosis of cultured VSMCs, which is known to be implicated in plaque rupture 15) .…”

“…It may induce ICAM-1 and MCP-1 expression in cultured HUVECs 14) , and induce apoptosis of cultured VSMCs, which is known to be implicated in plaque rupture 15) . PR-39, a cathelicidin family member in pigs, has been reported to play cardioprotective roles, such as limiting infarction size and proangiogenic function 16,17) ; however, there is lack of sequence and structural similarities between LL-37 and PR-39 16) .…”

LL-37-induced host cell cytotoxicity depends on cellular expression of the globular C1q receptor (p33)

“…Under pathological conditions, high levels of LL-37 have been found to reduce cell viability and promote apoptosis in osteoblasts, vascular smooth muscle cells, periodontal ligament cells, neutrophils, airway epithelial cells and T cells [10][11][12][13][14][15]. Notably, very high concentrations, exceeding several 100 µM of LL-37, have been detected in lesions from patients suffering from the autoimmune diseases psoriasis, rosacea and ulcerative colitis, suggesting an important role of LL-37 in these disease processes [16][17][18].…”

Characterization of the psycho-neuro-immunological state in patients with coronary artery disease

“…The association observed between the MLR and LL-37 is not surprising, as monocytes and derived macrophages are known to release LL-37 in atherosclerotic lesions [98,101].…”

“…It can be expressed by monocytes/macrophages, neutrophils, natural killer cells and epithel cells [98][99][100]. It was found that LL-37 could be produced also by macrophages in atherosclerotic lesions [98,101].…”