Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata

Chad E Brokopp ¹, Roman Schoenauer , Peter Richards

⁰Cardiovascular Research, Institute of Physiology, Zurich University, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

European Heart Journal +

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February 5, 2011

View abstract on PubMed

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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