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Cellular and Molecular Life Sciences (2018) 75:1349–1362
https://doi.org/10.1007/s00018-017-2723-6
REVIEW
Cardiomyokines from the heart
Ayano Chiba
1
· Haruko Watanabe‑Takano
1
· Takahiro Miyazaki
1
· Naoki Mochizuki
1,2
Received: 7 July 2017 / Revised: 21 November 2017 / Accepted: 27 November 2017 / Published online: 13 December 2017
© Springer International Publishing AG, part of Springer Nature 2017
Abstract
The heart is regarded as an endocrine organ as well as a pump for circulation, since atrial natriuretic peptide (ANP) and
brain natriuretic peptide (BNP) were discovered in cardiomyocytes to be secreted as hormones. Both ANP and BNP bind
to their receptors expressed on remote organs, such as kidneys and blood vessels; therefore, the heart controls the circula-
tion by pumping blood and by secreting endocrine peptides. Cardiomyocytes secrete other peptides besides natriuretic
peptides. Although most of such cardiomyocyte-derived peptides act on the heart in autocrine/paracrine fashions, several
peptides target remote organs. In this review, to overview current knowledge of endocrine properties of the heart, we focus
on cardiomyocyte-derived peptides (cardiomyokines) that act on the remote organs as well as the heart. Cardiomyokines act
on remote organs to regulate cardiovascular homeostasis, systemic metabolism, and inflammation. Therefore, through its
endocrine function, the heart can maintain physiological conditions and prevent organ damage under pathological conditions.
Keywords sPLA
2
· FSTL1 · ET1 · CHGA · FGF21
Introduction
The heart functions not only as an essential pump but also
as an endocrine organ to maintain homeostasis of the cir-
culatory system [1]. The discovery of atrial natriuretic pep-
tide (ANP) indicates the heart as an endocrine organ. In
the middle of 20th century, researchers who used electron
microscopes observed granules in atrial cardiomyocytes that
resembled those found in endocrine glands. These observa-
tions let them consider the possibility that atrial cardiomyo-
cytes might function as hormone-secreting cells [2]. In 1981,
de Bold et al. demonstrated endocrine properties of the heart
[3]. The extract of rat atrial cardiomyocytes contained pep-
tides that exerted potent natriuretic and diuretic effects when
it was injected in rats. The peptide was identified by several
groups and named ANP or atrial natriuretic factor (ANF)
[4–7]. The identification of ANP acting on kidneys revealed
that the heart functioned as an endocrine organ. After the
discovery of ANP, structurally and functionally related pep-
tides including brain natriuretic peptide (BNP) and C-type
natriuretic peptide (CNP) were identified [8, 9]. These pep-
tides are referred to as the natriuretic peptide (NP) family.
Cardiomyocytes also secrete other peptide hormones
besides natriuretic peptides (NPs) through secretory gran-
ules [10]. In addition to peptides, lipids and genetic materi-
als including mRNAs, DNAs, and non-coding RNAs are
secreted from cardiomyocytes through extracellular vesicles
[11]. The word ‘cardiokine’ is used to describe proteins
secreted from cardiomyocytes, cardiac fibroblasts, endothe-
lial cells, and smooth muscle cells in response to changes
in the cardiac environment [10, 12]. Particularly, proteins
secreted from cardiomyocytes are referred to as ‘cardio-
myokines’ [13]. Therefore, ANP and BNP are considered
to belong to cardiomyokines. Cardiomyokines are predicted
to play physiological and pathological roles in the heart and
remote organs. Although most of cardiomyokines act on the
heart in autocrine or paracrine fashions, some of them exert
endocrine actions (Fig. 1). In this review, by focusing on the
regulation and function of cardiomyokines, we overview the
current knowledge of the heart as an endocrine organ.
Cellular andMolecular Life Sciences
* Naoki Mochizuki
nmochizu@ri.ncvc.go.jp
1
Department of Cell Biology, National Cerebral
and Cardiovascular Center Research Institute, 5-7-1
Fujishirodai, Suita, Osaka 565-8565, Japan
2
AMED-CREST, National Cerebral and Cardiovascular
Center Research Institute, 5-7-1 Fujishirodai, Suita,
Osaka 565-8565, Japan
@Phil_Robichaud
@deepthiw
@JoseServera