Abstract | BACKGROUND: METHODS: We investigated the presence of LL-37 in human atherosclerotic lesions obtained at autopsy using immunohistochemistry. The direct effects of LL-37 on cultured vascular smooth muscle cells and isolated neutrophil granulocytes were investigated with morphological, biochemical and flow cytometry analysis. RESULTS: The neointima of atherosclerotic plaques was found to contain LL-37-like immunoreactivity, mainly in macrophages. In cultured smooth muscle cells, LL-37 at 30 mug/ml caused cell shrinkage, membrane blebbing, nuclear condensation, DNA fragmentation and an increase in caspase-3 activity as studied by microscopy, ELISA and enzyme activity assay, respectively. Flow cytometry demonstrated that LL-37 in a subset of the cells caused a small but rapidly developing increase in membrane permeability to propidium iodide, followed by a gradual development of FITC- annexin V binding. Another cell population stained heavily with both propidium iodide and FITC- annexin V. Neutrophil granulocytes were resistant to these effects of LL-37. CONCLUSION: This study shows that LL-37 is present in atherosclerotic lesions and that it induces death of vascular smooth muscle cells. In a subset of cells, the changes indicate the development of apoptosis triggered by an initial mild perturbation of plasma membrane integrity. The findings suggest a role for LL-37 as a mediator of immune cell-induced death of vascular smooth muscle cells in atherosclerosis.
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Authors | Cristina D Ciornei, Hans Tapper, Anders Bjartell, Nils H Sternby, Mikael Bodelsson |
Journal | BMC cardiovascular disorders
(BMC Cardiovasc Disord)
Vol. 6
Pg. 49
(Dec 20 2006)
ISSN: 1471-2261 [Electronic] England |
PMID | 17181861
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Annexin A5
- Antimicrobial Cationic Peptides
- FITC-annexin A5
- Lipopolysaccharides
- Propidium
- L-Lactate Dehydrogenase
- Caspase 3
- Fluorescein-5-isothiocyanate
- Cathelicidins
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Topics |
- Animals
- Annexin A5
- Antimicrobial Cationic Peptides
(analysis)
- Aorta
(cytology)
- Apoptosis
(immunology, physiology)
- Atherosclerosis
(physiopathology)
- Caspase 3
(metabolism)
- Cell Membrane Permeability
(physiology)
- Cells, Cultured
- DNA Fragmentation
- Flow Cytometry
- Fluorescein-5-isothiocyanate
(analogs & derivatives)
- Humans
- Immunohistochemistry
- L-Lactate Dehydrogenase
(metabolism)
- Lipopolysaccharides
(analysis)
- Muscle, Smooth, Vascular
(cytology, metabolism)
- Neutrophils
- Propidium
- Rats
- Cathelicidins
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