Dataset Information

Magnetic resonance imaging of infarct-induced canonical wingless/integrated (Wnt)/?-catenin/T-cell factor pathway activation, in vivo.

ABSTRACT:

Aims

Combined magnetic resonance imaging (MRI) of molecular and morpho-functional changes might prove highly valuable for the elucidation of pathological processes involved in the development of cardiac diseases. Our aim was to test a novel MRI reporter gene for in vivo assessment of the canonical Wnt/?-catenin/TCF pathway activation, an important regulator of post-ischaemic cardiac remodelling.

Methods and results

We designed and developed a chimeric construct encoding for both of iron-binding human ferritin heavy chain (hFTH) controlled by the ?-catenin-responsive TCF/lymphoid-enhancer binding factor (Lef) promoter and constitutively expressed green fluorescent protein (GFP). It was carried by adeno-associated virus serotype 9 (rAAV9) vectors and delivered to the peri-infarct myocardium of rats subjected to coronary ligation (n = 11). By 1.5 T MRI and a multiecho T2* gradient echo sequence, we detected iron accumulation only in the border zone of the transduced infarcted hearts. In the same cardiac area, post-mortem histological analysis confirmed the co-existence of iron accumulation and GFP. The iron signal was absent when rats (n = 6) were chronically treated with SEN195 (10 mg/kg/day), a small-molecular inhibitor of ?-catenin/TCF-dependent gene transcription. Canonical Wnt pathway inhibition attenuated the post-ischaemic remodelling process, as demonstrated by the significant preservation of cardiac function, the 42 ± 1% increase of peri-infarct arteriolar density and 43 ± 3% reduction in infarct scar size compared with untreated animals.

Conclusions

The TCF/Lef promoter-hFTH construct is a novel and reliable MRI reporter gene for in vivo detection of the canonical Wnt/?-catenin/TCF activation state in response to cardiac injury and therapeutic interventions.

SUBMITTER: Matteucci M

PROVIDER: S-EPMC5853574 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

Magnetic resonance imaging of infarct-induced canonical wingless/integrated (Wnt)/β-catenin/T-cell factor pathway activation, in vivo.

Matteucci Marco M Casieri Valentina V Gabisonia Khatia K Aquaro Giovanni Donato GD Agostini Silvia S Pollio Giuseppe G Diamanti Daniela D Rossi Marco M Travagli Massimiliano M Porcari Valentina V Recchia Fabio A FA Lionetti Vincenzo V

Cardiovascular research 20160926 3

<h4>Aims</h4>Combined magnetic resonance imaging (MRI) of molecular and morpho-functional changes might prove highly valuable for the elucidation of pathological processes involved in the development of cardiac diseases. Our aim was to test a novel MRI reporter gene for in vivo assessment of the canonical Wnt/β-catenin/TCF pathway activation, an important regulator of post-ischaemic cardiac remodelling.<h4>Methods and results</h4>We designed and developed a chimeric construct encoding for both o ...[more]

PMID: 27671803

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