TABLE 1.

Exercise-induced peptides mediate MI.

Names	Secreted cells	Functions	Main modulation mechanisms	References
GDF15	Cardiomyocytes	Inhibit inflammation	Repress PMN recruitment by directly inhibiting chemokine signaling and integrin activation	Kempf et al., 2011
FSTL1	Fibroblasts, cardiomyocytes	Inhibit inflammation and cardiac fibrosis, promote angiogenesis	Attenuate the migratory and proliferative capabilities of cardiac fibroblasts and expression of extracellular matrix proteins	Maruyama et al., 2016
Irisin	Cardiomyocytes	Reduce apoptosis; induce cardiac regeneration	Suppress the opening of mitochondrial permeability transition and protect mitochondria function; promote the function of cardiac progenitor cells	Wang H. et al., 2017; Zhao et al., 2019
FGF21	Cardiomyocytes, cardiac endothelial cells	Attenuate ventricular remodeling and myocyte apoptosis, increase capillary density	Decrease pro-inflammatory cytokines levels in an adiponectin-dependent manner and decrease miR-145-mediated autophagy	Joki et al., 2015; Hu S. et al., 2018
IL-33	Cardiac fibroblasts	Inhibit apoptosis and inflammation, reduce cardiac fibrosis	Suppress macrophage infiltration and production of inflammatory cytokines, inhibit NF-κB and p38 MAPK pathways, induce M2 macrophage polarization	Yin et al., 2014; Li et al., 2019
NRG	Cardiac endothelial cells	Attenuate apoptosis	Attenuate endoplasmic reticulum stress by activating PI3K/AKT pathway	Fang et al., 2017
MIF	Cardiomyocytes, cardiac fibroblasts	Promote cardiomyocytes survival and regulate inflammation	Promoted CSCs survival, proliferation and endothelial differentiation, activate PI3K/AKT/mTOR and AMPK pathways	Cui et al., 2016
BDNF	Endothelial cells, myocardial cells	Promote angiogenesis, inhibit inflammation and ventricle remodeling	Targeting its functional receptor, tyrosine receptor kinase B	Wang et al., 2018
CTRP9	Cardiac endothelial cells	Attenuate cardiomyocyte death	Activation of ERK/MMP-9 and ERK/Nrf2 signaling, upregulation of anti-oxidative proteins	Yan et al., 2017

BDNF, brain-derived neurotrophic factor; CTRP9, C1q/tumor necrosis factor-related protein-9; CSCs, cardiac stem cells; ERK, extracellular signal-regulated kinase; FSTL1, follistatin-like 1; FGF21, fibroblast growth factor 21; GDF15, growth differentiation factor 15; IL, interleukin; MI, myocardial infarction; MIF, migration inhibitory factor; miR, microRNA; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; MMP, matrix metalloproteinases; NRG, neuregulin; NF-κB, nuclear factor-κB; PMN, polymorphonuclear leukocytes; PI3K/AKT, phosphatidylinositol-3-kinase/protein kinase B.