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Follistatin-like 1 and its paralogs in heart development and cardiovascular disease

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Abstract

Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels and a leading cause of death worldwide. Thus, there is a need to identify new cardiokines that may protect the heart from damage as reported in GBD 2017 Causes of Death Collaborators (2018) (The Lancet 392:1736–1788). Follistatin-like 1 (FSTL1) is a cardiokine that is highly expressed in the heart and released to the serum after cardiac injury where it is associated with CVD and predicts poor outcome. The action of FSTL1 likely depends not only on the tissue source but also post-translation modifications that are target tissue- and cell-specific. Animal studies examining the effect of FSTL1 in various models of heart disease have exploded over the past 15 years and primarily report a protective effect spanning from inhibiting inflammation via transforming growth factor, preventing remodeling and fibrosis to promoting angiogenesis and hypertrophy. A better understanding of FSTL1 and its homologs is needed to determine whether this protein could be a useful novel biomarker to predict poor outcome and death and whether it has therapeutic potential. The aim of this review is to provide a comprehensive description of the literature for this family of proteins in order to better understand their role in normal physiology and CVD.

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Abbreviations

AA:

Amino acid

ACS:

Acute coronary syndrome

ACVR2B:

Activin A receptor type 2B

ATP1A1:

ATPase Na+/K+ transporting subunit alpha 1

BMP:

Bone morphogenetic protein

CAA:

Coronary artery aneurysms

circRNA:

Circular RNA

CVD:

Cardiovascular disease

DIP2A:

Disco-interacting protein 2 homolog A

FS:

Follistatin

FST:

Follistatin

FSTL:

Follistatin-like

GWAS:

Genome-wide association studies

HFpEF:

Heart failure with preserved ejection fraction

I/R:

Ischemia/reperfusion

LAD:

Left anterior descending

LoF:

Loss-of-function

LV:

Left ventricular

MI:

Myocardial infarction

miRNA:

MicroRNA

ncRNAs:

Non-coding RNAs

PCI:

Percutaneous coronary intervention

SPARC:

Secreted protein acidic and cysteine rich

SPIG1:

SPARC-related protein containing immunoglobulin domain 1

TAC:

Transverse aortic constriction

TGF:

Transforming growth factor

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Funding

This work was funded in part by the National Institutes of Health grants R21 AI145356, R21 AI152318, and R21 AI154927 and the American Heart Association 20TPA35490415 to DF. This study has received support from RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), Horizon 2020 Teaming 2 project (857560), and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_04369/ 0009632 and CZ.02.1.01/0.0/0.0/15_003/ 0000469). Moreover, the study was funded by grant no. NU22-02–00418 by the Ministry of Health of the Czech Republic.

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Authors and Affiliations

  1. Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 625 00, Czech Republic

    Martin Horak & Julie Bienertova-Vasku

  2. Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 5, Brno, 625 00, Czech Republic

    Martin Horak, Piia Kokkonen, David Bednar & Julie Bienertova-Vasku

  3. Department of Cardiovascular Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    DeLisa Fairweather

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  1. Martin Horak
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  2. DeLisa Fairweather
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  3. Piia Kokkonen
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  4. David Bednar
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  5. Julie Bienertova-Vasku
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Contributions

The whole team participated in the preparation of the manuscript, while Martin Horak conceived the idea and prepared the initial draft, Piia Kokkonen and David Bednar provided the database analyses and provided valuable insight into the functional aspects of FSTL1 and its paralogs. DeLisa Fairweather critically reviewed the manuscript and provided valuable insight into the practical implications of use of FSTLs as biomarkers in cardiology. Julie Bienertova-Vasku provided guidance for manuscript preparation by Martin Horak and critically reviewed the manuscript.

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Correspondence to Julie Bienertova-Vasku.

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Horak, M., Fairweather, D., Kokkonen, P. et al. Follistatin-like 1 and its paralogs in heart development and cardiovascular disease. Heart Fail Rev 27, 2251–2265 (2022). https://doi.org/10.1007/s10741-022-10262-6

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