TABLE 3.

Secreted FGFs involved in/against cardiac pathogenicity and their potential as serum biomarker in diseases.

FGF ligands	Alteration	Effect/application	Diseases/complications	Other cardiac clinical manifestation	References
FGF2	Elevation	Causative	TGFβ1-induced heart disorders	• Hypertrophic reaction and fibrosis	•Matsumoto et al., 2013
		Causative	Pericardial effusion in coronary artery disease (CAD)	• Accumulation ofpericardial fluid, intrapericardial pressure and cardiac dysfunction	•Karatolios et al., 2012
		Biomarker	Type 4 cardiorenal syndrome (CRS)	• Cardiac hypertrophy and attenuated ejection fraction (EF)	•Liu et al., 2015
LMW FGF2*	Elevation	Protective	TGFβ1-induced heart disorders	• Against fibrosis and chamber remodeling	•Svystonyuk et al., 2015
FGFs 8 and 10	Mutation	Causative	Conotruncal defects	• Abnormal heart development	Sun K. et al., 2020
FGF 15/19	Attenuation	Protective/biomarker	Atherosclerosis and CAD	• Angina, myocardial infarction (MI), and sudden cardiac death	•Itoh et al., 2016
FGF16	Mutation	Causative	Congenital metacarpal 4–5 fusion	• MI and atrial fibrillation	•Laurell et al., 2014
	Elevation	Protective	TGFβ1-induced heart disorders	• Anti-hypertrophic and anti-fibrotic actions	•Matsumoto et al., 2013
FGF21	Elevation	Biomarker	Atrial fibrillation in rheumatic heart	• Atrial arrhythmia and fibrosis	•Wang R. et al., 2015; Hui et al., 2018
			Atherosclerosis and CAD	• Cardio-metabolic disorders	•Shen et al., 2013; Kim et al., 2015; Xiao et al., 2015; Wu et al., 2020
			Heart failure	• Reduced EF, cardiac cachexia, non-acute and acute MI	•Zhang W. et al., 2015; Refsgaard Holm et al., 2019
		Protective	DCM	• Attenuation of cardiac apoptosis, fibrosis lipotoxicity, and dysfunction	•Zhang C. et al., 2015; Chen et al., 2018; Yang et al., 2018
FGF23	Elevation	Causative	Myocardial fibrosis	• Induction of fibrosis in cardiac fibroblasts and adverse structural and functional cardiac events	•Ding et al., 2019
		Causative/biomarker	Atrial fibrillation, CAD and atherosclerosis	• Kawasaki syndrome cardiac complications and advanced vascular plaque calcification	•Falcini et al., 2013; Mathew et al., 2014; Chua et al., 2019; Holden et al., 2019
		Causative	Chronic kidney disease- associated cardiac complications	• Hypertension, left ventricular hypertrophy, reduced contracting potential, arrhythmogenicity and accelerated cardiac aging	•Touchberry et al., 2013; Andrukhova et al., 2014; Grabner et al., 2015, 2017; Navarro-García et al., 2019
		Biomarker	Heart failure, myocarditis and dilative cardiomyopathy	• Chronic systolic, congestive and acute decompensated heart failure, reduced and preserved EF and recurrent major cardiovascular events	•Lutsey et al., 2014; Richter M. H. et al., 2015; Wohlfahrt et al., 2015; Bergmark et al., 2018; von Jeinsen et al., 2019
	Temporary elevation	Biomarker	Type 4 CRS	• Hypertrophy and reduced EF	•Verhulst et al., 2017

*LMW FGF2, low-molecular-weight isoform of FGF2.