Dataset Information

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

ABSTRACT:

Aims

Collagen degradation in atherosclerotic plaques with thin fibrous caps renders them more prone to rupture. Fibroblast activation protein (FAP) plays a role in arthritis and tumour formation through its collagenase activity. However, the significance of FAP in thin-cap human fibroatheromata remains unknown.

Methods and results

We detected enhanced FAP expression in type IV-V human aortic atheromata (n = 12), compared with type II-III lesions (n = 9; P < 0.01) and healthy aortae (n = 8; P < 0.01) by immunostaining and western blot analyses. Fibroblast activation protein was also increased in thin-cap (<65 µm) vs. thick-cap (? 65 µm) human coronary fibroatheromata (n = 12; P < 0.01). Fibroblast activation protein was expressed by human aortic smooth muscle cells (HASMC) as shown by colocalization on immunofluorescent aortic plaque stainings (n = 10; P < 0.01) and by flow cytometry in cell culture. Although macrophages did not express FAP, macrophage burden in human aortic plaques correlated with FAP expression (n = 12; R(2)= 0.763; P < 0.05). Enzyme-linked immunosorbent assays showed a time- and dose-dependent up-regulation of FAP in response to human tumour necrosis factor ? (TNF?) in HASMC (n = 6; P < 0.01). Moreover, supernatants from peripheral blood-derived macrophages induced FAP expression in cultured HASMC (n = 6; P < 0.01), an effect abolished by blocking TNF? (n = 6; P < 0.01). Fibroblast activation protein associated with collagen-poor regions in human coronary fibrous caps and digested type I collagen and gelatin in vitro (n = 6; P < 0.01). Zymography revealed that FAP-mediated collagenase activity was neutralized by an antibody directed against the FAP catalytic domain both in HASMC (n = 6; P < 0.01) and in fibrous caps of atherosclerotic plaques (n = 10; P < 0.01).

Conclusion

Fibroblast activation protein expression in HASMC is induced by macrophage-derived TNF?. Fibroblast activation protein associates with thin-cap human coronary fibroatheromata and contributes to type I collagen breakdown in fibrous caps.

SUBMITTER: Brokopp CE

PROVIDER: S-EPMC3205479 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Brokopp Chad E CE Schoenauer Roman R Richards Peter P Bauer Stefan S Lohmann Christine C Emmert Maximilian Y MY Weber Benedikt B Winnik Stephan S Aikawa Elena E Graves Kirk K Genoni Michele M Vogt Peter P Lüscher Thomas F TF Renner Christoph C Hoerstrup Simon P SP Matter Christian M CM

European heart journal 20110202 21

<h4>Aims</h4>Collagen degradation in atherosclerotic plaques with thin fibrous caps renders them more prone to rupture. Fibroblast activation protein (FAP) plays a role in arthritis and tumour formation through its collagenase activity. However, the significance of FAP in thin-cap human fibroatheromata remains unknown.<h4>Methods and results</h4>We detected enhanced FAP expression in type IV-V human aortic atheromata (n = 12), compared with type II-III lesions (n = 9; P < 0.01) and healthy aorta ...[more]

PMID: 21292680

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Dataset Information

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

Aims

Methods and results

Conclusion

Publications

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

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