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Fibroblast-Derived 3D Matrix System Applicable to Endothelial Tube Formation Assay
Published on: December 26, 2019
Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata
Chad E Brokopp1, Roman Schoenauer, Peter Richards
1Cardiovascular Research, Institute of Physiology, Zurich University, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
European Heart Journal
|February 5, 2011
Summary
Fibroblast activation protein (FAP) is elevated in thin-cap atherosclerotic plaques, where it degrades collagen. Macrophage-derived TNFα induces FAP in smooth muscle cells, contributing to plaque instability.
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Pathology
Background:
- Collagen degradation in atherosclerotic plaques with thin fibrous caps increases rupture risk.
- Fibroblast activation protein (FAP) has collagenase activity relevant to arthritis and tumors.
- The role of FAP in thin-cap human fibroatheromata is currently unknown.
Purpose of the Study:
- To investigate the expression and function of FAP in human atherosclerotic plaques, particularly thin-cap fibroatheromata.
- To determine the cellular source and regulation of FAP in atherosclerosis.
- To assess the collagenolytic activity of FAP in atherosclerotic lesions.
Main Methods:
- Immunostaining and Western blot analysis of human aortic and coronary atherosclerotic lesions.
- Flow cytometry and immunofluorescence for FAP expression in human aortic smooth muscle cells (HASMC).
- ELISA to assess FAP regulation by TNFα and macrophage supernatants; in vitro collagen digestion assays; zymography.
Main Results:
- FAP expression was significantly enhanced in advanced human aortic atheromata (type IV-V) and thin-cap coronary fibroatheromata compared to earlier lesions and healthy aortae.
- FAP was expressed by HASMC, and its expression was upregulated by macrophage-derived TNFα.
- FAP localized to collagen-poor regions in fibrous caps, exhibited type I collagenolytic activity in vitro, and this activity was confirmed in plaque samples.
Conclusions:
- FAP expression in HASMC is induced by macrophage-derived TNFα.
- FAP is associated with thin-cap human coronary fibroatheromata.
- FAP contributes to type I collagen breakdown within atherosclerotic fibrous caps, potentially promoting plaque instability.
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