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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rohde, E; Schallmoser, K; Reinisch, A; Hofmann, NA; Pfeifer, T; Fröhlich, E; Rechberger, G; Lanzer, G; Kratky, D; Strunk, D.
Pro-angiogenic induction of myeloid cells for therapeutic angiogenesis can induce mitogen-activated protein kinase p38-dependent foam cell formation.
Cytotherapy. 2011; 13(4):503-512
Doi: 10.3109/14653249.2010.536214
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Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Rohde Eva
- Strunk Dirk
- Co-Autor*innen der Med Uni Graz
- Fröhlich Eleonore
- Hofmann Nicole
- Kratky Dagmar
- Lanzer Gerhard
- Pfeifer Thomas
- Reinisch Andreas
- Schallmoser Katharina
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- Abstract:
- Clinical trials for therapeutic angiogenesis use blood- or bone marrow-derived hematopoietic cells, endothelial progenitor cells (EPC) and mesenchymal stromal cells (MSC) for vascular regeneration. Recently concerns have emerged that all three cell types could also contribute to atherosclerosis by foam cell formation. Therefore, we asked whether human myelomonocytic cells, EPC or MSC can accumulate lipid droplets (LD) and develop into foam cells. LD accumulation was quantified by flow cytometry, confocal microscopy and cholesterol measurement in each of the cell types. The impact of an initial pro-angiogenic induction on subsequent foam cell formation was studied to mimic relevant settings already used in clinical trials. The phosphorylation state of intracellular signaling molecules in response to the pro-angiogenic stimulation was determined to delineate the operative mechanisms and establish a basis for interventional strategies. Foam cells were formed by monocytes but not by EPC or MSC after pro-angiogenic induction. Mitogen-activated protein kinase (MAPK) p38 phosphorylation was enhanced and kinase inhibition almost abrogated intracellular LD accumulation in monocytes. These data suggest that hematopoietic cell preparations containing monocytes bear the risk of foam cell formation after pro-angiogenic induction. Instead, EPC and MSC may drive vascular regeneration without atherogenesis aggravation. A thorough understanding of cell biology is necessary to develop new strategies combining pro-angiogenic and anti-atherogenic effects during cell therapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Cells, Cultured -
- Flow Cytometry -
- Foam Cells - cytology
- Foam Cells - metabolism
- Humans -
- Microscopy, Confocal -
- Myeloid Cells - cytology
- Myeloid Cells - metabolism
- Neovascularization, Physiologic - physiology
- Stem Cells - cytology
- Stem Cells - metabolism
- p38 Mitogen-Activated Protein Kinases - metabolism
- Find related publications in this database (Keywords)
- atherogenesis
- foam cell formation
- mitogen-activated protein kinase inhibition
- stem cell therapy
- therapeutic angiogenesis