FDG-PET reveals improved cardiac regeneration and attenuated adverse remodelling following Sitagliptin + G-CSF therapy after acute myocardial infarction.
Eur Heart J Cardiovasc Imaging
; 17(2): 136-45, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26420287
ABSTRACT
AIMS:
Dual therapy comprising G-CSF for mobilization of bone marrow-derived progenitor cells (BMPCs), with simultaneous pharmacological inhibition of dipeptidylpeptidase-IV for enhanced myocardial recruitment of circulating BMPC via the SDF-1α/CXCR4-axis, has been shown to improve survival after acute myocardial infarction (AMI). Using an innovative method to provide non-invasive serial in vivo measurements and information on metabolic processes, we aimed to substantiate the possible effects of this therapeutic concept on cardiac remodelling after AMI using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET). METHODS ANDRESULTS:
AMI was induced in C57BL/6 mice by performing surgical ligation of the left anterior descending artery in these mice. Animals were then treated with granulocyte-colony stimulating factor + Sitagliptin (GS) or placebo for a duration of 5 days following AMI. From serial PET scans, we verified that the infarct size in GS-treated mice (n = 13) was significantly reduced at Day 30 after AMI when compared with the mice receiving placebo (n = 10). Analyses showed a normalized FDG uptake on Day 6 in GS-treated mice, indicating an attenuation of the cardiac inflammatory response to AMI in treated animals. Furthermore, flow cytometry showed a significant increase in the anti-inflammatory M2-macrophages subpopulation in GS-treated animals. In comparing GS treated with placebo animals, those receiving GS-therapy showed a reduction in myocardial hypertrophy and left ventricular dilatation, which indicates the beneficial effect of GS treatment on cardiac remodelling. Remarkably, flow cytometry and immunohistochemistry showed an increase of myocardial c-kit positive cells in treated mice (n = 12 in both groups).CONCLUSION:
Using the innovative method of micro-PET for non-invasive serial in vivo measurements of metabolic myocardial processes in mice, we were able to provide mechanistic evidence that GS therapy improves cardiac regeneration and reduces adverse remodelling after AMI.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Granulócitos
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Tomografia por Emissão de Pósitrons
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Fosfato de Sitagliptina
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Infarto do Miocárdio
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur Heart J Cardiovasc Imaging
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha