The Role of Cardiokines in Heart Diseases: Beneficial or Detrimental?

Table 1

Summary of the physiological roles of cardiokines in cardiac diseases.

Cardiokine	Beneficial or; detrimental	Action; mechanisms	Dose-; response	Types of cardiac diseases	Predictor
Natriuretic peptide
ANP [11]	Beneficial	-	Yes	HF	-
BNP [3, 12–15]	Beneficial	-	Yes	HF	Yes
Interleukin
IL-33 [23–27]	Beneficial	IL-33/ST2, sST2	-	HF, MI, CH, MF	Yes (ST2)
IL-6 [95–97]	Detrimental	gp130	Yes	MI	Yes
IL-18 [98, 99]	Detrimental	-	-	CAHD	-
IL-1β [91–94]	Detrimental	NO synthase	-	CH, ACS	-
Follistatin
FSTL1 [30–38]	Beneficial	AMPK, BMP-4	-	MI, CH, HF	-
FSTL3 [131, 132]	Detrimental	-	-	CH	-
FGF
FGF21 [39–45]	Beneficial	β-Klotho, ERK	-	CAHD	-
FGF23 [109–113]	Harmful	ERK1/2	-	MF, CH	-
Sfrp
Sfrp-3 [46–50]	Beneficial	Wnt signaling	Yes	HF, MI	-
Sfrp-2 [51–54]	Protective	Wnt signaling, BMP-1/Tolloid-like metalloproteinase	-	MI	-
MIF [55–59]	Beneficial (the cardiogenic)	-	-	MI	-
NRG [60–62]	Beneficial	-	-	MI, MF	-
ADM [63–69]	Beneficial	-	Yes	MI, CAHD, MI	Yes
PI16 [70, 71]	Beneficial	KLF2, ERK5	-	CH, HF	-
Neurotrophins
MANF [72–74]	Beneficial	ATF6	-	MI, CH	-
CDNF [75]	Beneficial	-	-	MI	-
NDNF [76]	Beneficial	Focal adhesion kinase/Akt	-	MI	-
BDNF [77–81]	Beneficial	TrkB	-	MI	-
Ang-II [82–86]	Detrimental	TRPM7, AT1R, JNK,ERK	-	MF, HF	-
TNF-α [100–108]	Detrimental	PLA2/AA, PKA, Cx40	Yes	HF, ACS, Arrhythmia	-
MMPs [114–117]	Detrimental	TIMPs	-	HF, CAHD, ACS	-
PDGF [118–123]	Detrimental	PDGFR-α and PDGFR-β	-	MF, CAHD	-
TGF-β [34, 124–135]	Undetermined	TGF-β receptor 1/2	-	MI	-
CTRP9 [135–142]	Undetermined	gCTRP9, AdipoR1, AMPK, Akt	-	MI, HF, CH	-

ACS: acute coronary syndrome; ADM: adrenomedullin; Ang-II: angiotensin-II; AMPK: adenosine 5′-monophosphate-activated protein kinase; ANP: atrial natriuretic peptide; AT1R: Ang-II 1 receptor; ATF6: activating transcription factor 6; BDNF: brain-derived neurotrophic factor; Bmp1: bone morphogenic protein 1; BNP: brain natriuretic peptide; CAHD: coronary atherosclerotic heart disease; CDNF: cerebral dopamine neurotrophic factor; CH: cardiac hypertrophy; CTRP9: C1q/TNF-related protein 9; Cx40: connexin 40; ERK: extracellular regulated protein kinases; FGF: fibroblast growth factor; FSTL1: follistatin-like 1; GDF-15: growth differentiation factor-15; gp130: glycoprotein 130; HF: heart failure; IL: interleukin; JNK: c-Jun N-terminal kinase; MANF: mesoscopic astrocyte-like neurotrophic factor; MF: myocardial fibrosis; MI: myocardial infarction; MIF: macrophage migration inhibitory factor; MMPs: matrix metalloproteinases; NDNF: neuron-derived neurotrophic factor; NO: nitric oxide; PDGF: platelet-derived growth factor; PI16: protease inhibitor 16; PKA: protein kinase A; PLA2/AA: phospholipase A2/arachidonic acid; Sfrp-3: secreted frizzled-related protein-3; TGF-β: transforming growth factor-β; TIMP: tissue inhibitor of metalloproteinase; TNF-α: tumor necrosis factor-α; TRPM7: transient receptor potential melastatin-7 channels; TSC-36: transforming growth factor β-stimulated clone 36.