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Review
. 2022 Nov;27(6):2251-2265.
doi: 10.1007/s10741-022-10262-6. Epub 2022 Jul 22.

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

Martin Horak  1   2 , DeLisa Fairweather  3 , Piia Kokkonen  2 , David Bednar  2 , Julie Bienertova-Vasku  4   5
Affiliations
Review

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

Martin Horak et al. Heart Fail Rev. 2022 Nov.

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.

Keywords: FSTL1; FSTL4; FSTL5; Heart failure; Inflammation.

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Conflict of interest statement

Conflict of interest

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The phylogenetic tree of homologous sequences with the FSTL1 protein.
A FASTA sequence of FSTL1 was used as a query for BLASTp search on human sequences. Only unique sequences with protein identity higher than 25% and e value lower than 0.1 are represented. The fnal phylogram was generated using the Interactive Tree Of Life (iTOL) online tool (Ref. Letunic, I., and Bork, P. (2019). Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res. 47, W256–W259.
Fig. 2
Fig. 2. Structural organization of the FSTL1, FSTL4, and FSTL5 proteins.
The circle represents post-translation modification, and the text above arrow represents specific amino acid residue and its position. The bottom arrows represent amino acid numbers in the specific domains. SIGN, signal sequence; FOLN, follistatin-like domain; KZ, Kazal-like domain; EF, EF-hand domain; VWC, von Willebrand factor type C domain; IG, immunoglobulin-like domain; WD40/YVTN, WD40/YVTN repeat-like-containing domain; Gly, glycosylation; P, phosphorylation; N, asparagine; S, serine.
Fig. 3
Fig. 3. FSTL1 signaling pathways in cardiovascular diseases.
Schematic representation of signaling pathways modulated by FSTL1 in response to cardiac injury. The black arrows indicate promotion/activation, and broken red arrows indicate inhibition. The question marks represent unknown receptors.
See this image and copyright information in PMC

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