Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes

Table 1

Biological effects and HF-related actions of myokines.

Name of myokine	Affiliation	Origin of myokines	Biological action	HF-related actions	References
Decorin	Proteoglycan	Skeletal muscles, fibroblasts, vascular endothelial cells, cardiac myocytes, and smooth muscle cells	↓ Accumulation of ECM, ↑ cell differentiation, ↑ proliferation, and ↓ apoptosis	Downregulated in HF; ↓ Cardiac hypertrophy, ↑ cardiac fibrosis	[41–49]
Irisin	Muscle tissue-secreted peptide FNDC5	Skeletal muscles, myocardium	↑ Expenditure, ↑ oxidative metabolism, ↑ myoblast differentiation, ↑ glucose uptake	Downregulated in HF; ↓ Tolerance to physical exercise, ↑ skeletal muscle hypotrophy	[50–71]
Myonectin	CTRP15	Skeletal muscles, adipose tissue	↑ Oxidation of free fatty acid, ↑ oxidative metabolism, ↑ myoblast differentiation, ↑ glucose uptake	Downregulated in HF; ↑ Skeletal muscle hypotrophy	[72–77]
FGF-21	FGF super family	Cardiac myocytes, pancreas, adipose tissue, liver, brain, and kidney	↑ Glucose uptake and protein synthesis in skeletal muscle, ↓ lipolysis in WAT, ↑ browning of WAT	Downregulated in HF; ↑ Skeletal muscle mass, ↓ IR, ↑ exercise tolerance	[78–94]
Myostatin	TGF-β superfamily	Cardiac myocytes, skeletal muscles	↑ Skeletal muscle fiber-type switches, ↓ fast myosin heavy-chain expression, ↓ differentiation of myoblasts, ↑ ubiquitin-proteasomal activity in myocytes and ILGF-PKB pathway	Upregulated in HF; ↑ Skeletal muscle hypotrophy, ↑IR, ↑ autophagy, ↑ muscle weakness, ↓ exercise tolerance	[95–111, 203]
BDNF	Neurotrophin family	Cardiac myocytes, skeletal muscles, smooth muscle cells, endothelial cells, astrocytes	↑ Myoblast proliferation, ↑ neurogenesis, ↑ angiogenesis, ↑ vascular reparation	Downregulated in HF; ↑ Tolerance to physical exercise	[112–134]
IL-8	Cysteine-X-cysteine family of chemokines	Mononuclears, phagocytes, adipocytes, epithelial cells, endothelial cells, and mesenchymal cells	↓ Glucose disposal, ↑ IR	Upregulated in HF; ↓ Skeletal muscle energy metabolism	[135–147]
IL-15	Pleiotropic cytokine with structural similarity with IL-2	Cardiac myocytes, mononuclear phagocytes	Anabolic effect, ↓ oxidative stress	Downregulated in HF; ↑ Tolerance to physical exercise, ↑ skeletal muscle mass, ↓ WAT, ↓ apoptosis of cardiac myocytes and myoblasts	[149–168]
GDF-11	TGF-β super family	Skeletal muscle, neural stem cells, and cardiac myocytes	↓ Differentiation of myoblasts, angiogenesis, and neovascularization	Downregulated in HF; ↓ Physical endurance, ↑ skeletal muscle hypotrophy and weakness	[169–178]
Osteonectin	SPARC protein	Cardiac myocytes, skeletal muscles, adipose tissue, bones, mucosa, vasculature, kidney, liver	Potential mediator of collagen deposition and extracellular matrix remodeling	Upregulated in HF; Predictor of poor HF outcomes, ↑ cardiac contractility and reparation at early stage, ↓ cardiac myocyte survival and vascular integrity at late stage	[179–196]

FGF-21: fibroblast growth factor-21; TGF-β: transforming growth factor-beta; IR: insulin resistance; ILGF-PKB: insulin-like growth factor-protein kinase B; WAT: white adipose tissue; GDF-11: growth differentiation factor-11; ECM: extracellular matrix; SPARC: secreted protein acidic and rich in cysteine.