Table 1.

Exercise Regulates Cytokines in Cardiovascular Diseases

Cytokines	Subjects		Exercise intervention program			Main mechanism	Main biological action	Cardiovascular diseases	Reference
	Model	Sample size	Type	Intensity	Duration
UCP2	Mice	ND	Treadmill running	Exhausted	ND	UCP2/AMPK/Akt/FoxO1	Autophagy↑ and oxidation resistance↑	Atherosclerosis	71
FUNDC1	Mice	ND	Endurance swim training	70% maximal power	5 d/wk; 90 min/d; 4 wk	PPARγ/FUNDC1/LC3	Mitophagy↑ and IRI↓	Atherosclerosis	72
PGC‐1α	Rats	ND	Swimming training	3 h/session, 2 times, separated by 45 min	1 d	P38γMAPK/ATF2/PGC‐1α/VEGF	Mitochondrial biogenesis↑ and angiogenesis↑	Atherosclerosis	41
Irisin	Mice	45	Treadmill running	HIIT and MICT	3 times/wk; 23 min/set; 6 wk	PGC‐1a/FNDC5/irisin	Mitochondrial oxidative damage↓ and blood lipid ↓	Atherosclerosis	77
FGF21	Mice	40	Treadmill running and ladder‐climbing	76% of VO2max and 75% of the maximum load	5 d/wk; 4 wk and 3 times/set, 9 sets/d, 4 wk	FGF21/TGF‐β1/Smad2/3/MMP2/9	Mitochondrial biogenesis↑, oxidative stress↓, cell apoptosis↓ and cardiac fibrosis↓	Ischemic heart disease	83
Musclin	Mice	40	Treadmill running	15 m/min at 5° inclination, 45 min	5 d/wk, 3 wk	cGMP/PKGI/CREB/PGC‐1α	Mitochondrial biogenesis↑	Ischemic heart disease	82
SIRT1	Human; rats	70	Treadmill running	10m/min, 5 min (40%–50% VO2max); 13 m/min, 5 min; 16 m/min, 50 min(60%–70% VO2max)	5d/wk, 3wk	SIRT1/PGC‐1α/PI3K/Akt	Mitochondrial integrity and biogenesis↑	Ischemic heart disease	78
HSP70	Healthy mAu: ale	11	Cycling	30 min at 55% VO2max, 20 min at 70% VO2max and until exhaustion (10 min) at 80% of VO2max	60 min, 1 session	HSP70/TLR4/ERK/p38MAPK/HSP27	Mitochondrial protein folding↑, cell proliferation and angiogenesis↑	Ischemic heart disease	92, 93
FGF21	Mice	20	Treadmill running	9 m/min	5 d/wk, 1 h/d, 6 wk	AMPK/FOXO3/SIRT3	Toxic lipid‐induced mitochondrial dysfunction↓ and oxidative stress↓	Diabetic cardiomyopathy	99
Mhrt779	mice	72	Swimming training	15 min/session, 2 times/d, +15min/2 d → 90 min/session, 90 min/session, 2 times/d, 7 d	21 d	Mhrt779/Brg1/Hdac2/Akt/p‐GSK3β	Mitochondrial protein posttranslation modification↑ and antihypertrophic effects↑	Hypertrophic cardiomyopathy	97
c‐Ddx	Mice	72	Swimming training	15 min/session, 2 times/d, +15 min/2 d → 90 min/session, 90 min/session, 2 times/day, 7 d	21 d	c‐Ddx/AMPK/eEF2	Mitochondrial protein degradation↑ and antihypertrophic memory pretreatment↑	Hypertrophic cardiomyopathy	98
IL‐6	healthy male	6	One‐legged knee extensor exercise	40% W max, ke	5 h	IL‐6/SERCA2a	Cardiotoxicity of doxorubicin and mitochondrial oxidative stress↓	Dilated cardiomyopathy	108

“↑” indicates improve; “↓”, decrease; +15 min/2 d → 90 min/session, increased by 15 min every 2 d until 90 min/session; 38MAPK: p38 mitogen‐activated protein kinase; Akt, protein kinase B; AMPK, adenosine5′‐monophosphate‐activated protein kinase; ATF2, activating transcription factor 2; Brg1, brahma‐related gene 1; c‐Ddx, circ‐Ddx60; cGMP, cyclic guanosine monophosphate; CREB, cyclic adenosine monophosphate response element binding; d, day(s); eEF2, eukaryotic translation elongation factor 2; ERK, extracellular signal‐regulated protein kinases; FGF21, fibroblast growth factor 21; FNDC5, fibronectin type III domain‐containing protein 5; FoxO1, forkhead box O1; FUNDC1, FUN14 domain containing 1; Hdac2, histone deacetylase 2; HIIT, high‐intensity interval training; HSP, heat shock protein; IL‐6, interleukin‐6; IRI, ischemia–reperfusion injury; ke, knee extensor peak power output; LC3, light chain 3; Mhrt779, long noncoding myosin heavy chain‐associated RNA transcript; MICT, moderate‐intensity continuous training; MMP, matrix metalloproteinase; ND, not determined; PGC‐1α, peroxisome proliferator‐activated receptor‐gamma coactivator 1alpha; p‐GSK3β, phosphorylated glycogen synthase kinase 3β; PI3K, phosphatidylinositol‐3‐hydroxykinase; PKGI, type I cGMP‐dependent protein kinases; PPARγ; peroxisome proliferator‐activated receptor γ; SERCA2a, sarcoplasmic reticulum calcium ATPase 2a; SIRT, sirtuin; Smad2/3, phospho Thr8; TGF‐β, transforming growth factor‐beta; TLR4: toll‐like receptor 4; VEGF, vascular endothelial growth factor; and W _max: maximal watts.