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An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Enhanced procoagulatory activity (PCA) of human monocytes/macrophages after in vitro stimulation with chemically
P Schuff-Werner1, G Claus, V W Armstrong
1Department of Clinical Chemistry, Georg-August University, Göttingen, F.R.G.
Abstract:
In cultured human monocytes/macrophages, surface expression of procoagulatory activity (PCA) was induced by chemically modified LDL (acetyl-LDL and MDA-LDL) in a dose- and time-dependent manner. Maximum PCA (30-fold increase) was detected after 24 h of culture with modified LDL at doses of 25-750 micrograms protein/ml. Using factor VII deficient human plasma and phospholipase C this PCA was identified as tissue thromboplastin activity (factor III). These results suggest a further atherogenic potential for modified LDL through stimulation of the conversion of fibrinogen to fibrin in the atheromatous lesion.
Insights
Chemically modified LDL (low-density lipoprotein) significantly increases procoagulatory activity (PCA) in human monocytes/macrophages. This suggests modified LDL contributes to atherosclerosis by promoting blood clot formation within artery walls.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Immunology
Background:
- Modified low-density lipoprotein (LDL) is implicated in atherosclerosis.
- Monocytes/macrophages play a key role in atheromatous lesion development.
Purpose of the Study:
- To investigate the effect of chemically modified LDL on procoagulatory activity (PCA) in human monocytes/macrophages.
- To identify the nature of the induced PCA.
Main Methods:
- Cultured human monocytes/macrophages were treated with acetyl-LDL and MDA-LDL.
- Procoagulatory activity (PCA) was measured.
- Factor VII deficient plasma and phospholipase C were used for PCA identification.
Main Results:
- Modified LDL induced PCA in a dose- and time-dependent manner.
- Maximum PCA (30-fold increase) observed after 24 hours with 25-750 µg protein/ml modified LDL.
- PCA was identified as tissue thromboplastin activity (factor III).
Conclusions:
- Chemically modified LDL stimulates tissue thromboplastin activity in monocytes/macrophages.
- This suggests a pro-thrombotic role for modified LDL in atheromatous lesions.
- Modified LDL may promote fibrinogen to fibrin conversion, contributing to atherosclerosis.

