Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction.

Hoffmann, Daniel B.; Fraccarollo, Daniela ORCID; Galuppo, Paolo ORCID; Frantz, Stefan; Bauersachs, Johann GND; Tillmanns, Jochen ORCID

Introduction

Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI.

Materials and methods

We used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19).

Results

Healthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups.

Conclusion

We show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.

Cite

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Hoffmann, Daniel / Fraccarollo, Daniela / Galuppo, Paolo / et al: Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction.. 2021.

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