Details

Autor(en) / Beteiligte

• Nagaraju, Chandan K.
• Dries, Eef
• Popovic, Natasa
• Singh, Abhishek A.
• Haemers, Peter
• Roderick, H. Llewelyn
• Claus, Piet
• Sipido, Karin R.
• Driesen, Ronald B.

Titel

Global fibroblast activation throughout the left ventricle but localized fibrosis after myocardial infarction

Ist Teil von

• Scientific reports, 2017-09, Vol.7 (1), p.10801-14, Article 10801

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Fibroblast (Fb) differentiation and interstitial fibrosis contribute to cardiac remodeling and loss of function after myocardial infarction (MI). We investigated regional presence and regulation of fibrosis in a pig MI model. In vivo analysis of regional function and perfusion defined three regions: the scar, the myocardium adjacent to the scar (MI adjacent , reduced function, reduced perfusion reserve), and the remote myocardium (MI remote , minimal functional deficit, maintained perfusion). Interstitial and perivascular fibrosis, and increase of collagen type I, was only observed in the MI adjacent . Fb activated protein-alpha (FAP-α) was enriched in MI adjacent compared to MI remote . TGF-β1, which triggers Fb differentiation, was upregulated in both MI adjacent and MI remote , whereas lysyl oxidase, a regulator of collagen cross-linking, and the proteoglycans decorin and biglycan were only increased in the MI adjacent . Fb isolated and cultured for 4 days had myoFb characteristics with little difference between MI remote and MI adjacent , although RNA sequencing revealed differences in gene expression profiles. Fbs from all regions maintained proliferative capacity, and induced contraction of 3-D collagen matrices but scar myoFb was more effective. These data suggest that after MI, signaling through TGF-β1, possibly related to increased mechanical load, drives Fb activation throughout the left ventricle while regional signaling determines further maturation and extracellular matrix remodeling after MI.