Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

Table 1 Summary of endothelial progenitor cell levels in different disease populations

Disease	Results	Comments	Ref.
Aging	↓ EPCs proliferation		[20,22]
	↓ EPCs migration
	↓ EPCs survival
Coronary heart disease	↓ EPC activity		[29]
	↓ EPC migratory capacity
CHF	↑ EPC levels in mild stages[34,35]		[34-36]
	↑ EPC levels in acute exacerbation[36]
	↑ Late apoptotic progenitors[35]
	↓ EPC levels in advanced stages[34,35]
LVADs	↑ EPC levels		[38,39]
PAH	↑ EPC levels[42,45,46]	Conflicting results	[42-46]
	↓ EPC levels[43,44]
Critical illness	↑ EPC levels in sepsis and septic shock[47,49]		[47-49]
	↑ EPC levels in early acute lung injury[48]
COPD	↑ EPC levels[52]	Conflicting results	[52-56]
	↓ EPC levels[53,54]
	↑ EPC levels in exacerbation of COPD[55]
	↓ EPC mobilization and colony-forming capacity[56]
OSA	↑ EPC levels[58,60]	Conflicting results	[57-60]
	↓ EPC levels[59]
	- No difference[57]
Diabetes mellitus type Iand II	↓ EPC levels		[61-65]
Cerebrovascular disease	↓ EPC levels in stroke[66]		[66-69]
	- No difference in ischemic stroke[67]
	↑ EPC levels in acute ischemic stroke[67]
	↓ EPC levels in atherothrombotic cerebral ischemic event[68]
	↓ EPC colony forming in acute stroke[69]
PAD	↑ EPC levels in moderate phase		[71,72]
	↑ EPC levels in advance phase
Arterial hypertension	↑ EPC levels in early stage of hypertension[73]		[19,73,74]
	↓ EPC migratory capacity in CAD and hypertension[19]
	- No difference on EPC levels in pre-hypertensive and hypertensive[74]
Obesity	↓ EPC levels[75-77]		[75-79]
	↓ EPC colony forming capacity[76]

EPC: Endothelial progenitor cell; CHF: Chronic heart failure; LVAD: Left ventricular assist device; PAH: Pulmonary arterial hypertension; COPD: Chronic obstructive pulmonary disease; OSA: Obstructive sleep apnea; PAD: Peripheral arterial disease; CAD: Coronary artery disease.

Table 2 Effects of exercise training on endothelial progenitor cells in animals and healthy subjects

Subjects	n	Study group; age	Modality	Exercise prescription	Duration	Results	Limitations	Ref.
Mice	12	Exercise group; Control group	Aerobic	Exercise group: Voluntary running 5100 ± 800 m 7 d a week; Control group: No intervention	28 d	↑ EPCs		[101]
Healthy male	10	Exercise (n = 10) 59 ± 2 yr	Home based aerobic	Walking/jogging 60%-75% predicted peak HR 40-50 min-5-7 sessions per week	3 mo	↑ EPC colonies about 100% from 10 ± 3 to 22 ± 5; ↑ Migratory activity about 50% from 683 ± 96 to 1022 ± 123 RFUs	Non control study	[20]
Healthy male	47	Exercise: Elderly (n = 25) 67.8 ± 3.38 yr, young (n = 22) 26.3 ± 3.15 yr	Aerobic	Treadmill 30 min 3 sessions per week	12 wk	↑Re-endothelialization capacity of EPCs from 15% ± 4% to 36% ± 9%	Non control study	[102]
Healthy male (n = 7), female (n = 13)	20	Interval exercise: Moderate (n = 9), heavy (n = 11)	Aerobic	Ergometer moderate interval (10 s @ 120% peak work rate : 20 s @ 20 W); Heavy interval (30 s @ 120% peak work rate : 60 s @ 20 W), 30-40 min 3 sessions per week	6 wk	No significant change on EPC numbers	Non control study measurements took place 48 h after the last session	[103]
Children	182	Intervention (n = 109), control (n = 73)		Intervention group: PA at school 45 min + endurance training 15 min per school day; Control group: PA at school 45 min 2 school day per week	1 school year	↑ CPCs		[104]

EPC: Endothelial progenitor cell; PA: Physical activity.

Table 3 Effects of exercise training on endothelial progenitor cells in different disease populations

Subjects	n	Study group; age	Disease	Modality	Exercise prescription	Duration	Results	Limitations	Ref.
Mice	12	Exercise; Control	Advanced atherosclerotic lesions; Early atherosclerotic lesions	Aerobic	Voluntary running	8 wk	No change on advanced atherosclerotic lesions; ↑ EPC levels on early atherosclerotic lesions		[107]
Mice	10	Exercise; Control	After traumatic brain injury	Aerobic	Exercise group: Treadmill 22 m/min 30 min 7 d per week; Control group: No intervention	1 wk	↑ Neuronal stem cell		[108]
Male (n = 24); Female (n = 51)	64	Exercise (n = 32); Control (n = 32) 67.1 ± 8.4 yr old	Coronary artery disease	Aerobic + resistance exercise	Exercise group: Bicycle ergometer, treadmill, rowing, steps, arm ergometer + dumbbell, weight training 80% of HRmax 50 min + (5 min warm-up and 5 min cool down) 3 sessions per week	8 wk	No change		[109]
Male (n = 92); Female (n = 20)	112	Exercise (n = 112) 58.2 ± 9.5 yr old	After acute coronary syndrome	Aerobic	Exercise group: Bicycle ergometer 60%-70% of peak VO2 30 min + ( 5 min warm-up and 5 min cool down) 3 sessions per week	30 d	↑ EPC levels + ↓ pro-inflammatory markers	No controls; No homogeneity of population	[110]
Male (n = 20); Female (n = 10)	30	Exercise (n = 16); Control (n = 14) 67 ± 12 yr old	Hemodialysis	Aerobic	Exercise group: Treadmill/walking 50% max speed 10 min 2 sessions per day; Control group: No intervention	6 mo	No change	Small sample size; No standarized work	[111]
Male (n = 16); Female (n = 6)	22	Exercise (n = 22) 61.4 yr old (SE 1.60)	CHF NYHA II or III	Aerobic	Exercise group: Bicycle ergometer 60% of HR reserve 45 min + (5 min warm-up and 5 min cool down) 3 sessions per week	8 wk	↑ EPC levels	No controls; No homogeneity of population	[112]
Male (n = 30); Female (n = 8)	38	Exercise (n = 21) 61.3 ± 2.2 yr old; Control (n = 17) 63.4 ± 3 yr old	CHF	Aerobic	Exercise group: 90% HR 60 min 3 sessions per week; Control group: No intervention	6 mo	Improves CAC migratory capacity; ↑ EPC levels	No randomization	[113]
Male (n = 16); Female (n = 12)	28	Exercise (n = 14) 72 ± 11 yr old; Control (n = 14) 73 ± 11 yr old	CHF Exercise NYHA II; Control NYHAI	Calistenics + aerobic	Exercise group: Bicycle ergometer 75%-85% of HRmax 30 min 2 sessions per day 6 sessions per week; Control group: No intervention	3 wk	↑ EPC levels	Small sample size	[114]
Male	37	Exercise (n = 18) 60 ± 11 yr old; Control (n = 19) 62 ± 10 yr old	NYHA functional class IIIb	Aerobic + calisthenics + noncompetitive ball games	Exercise group: Bicycle ergometer in hospital (50% of VO2max 5-20 min, 3-6 sessions per day, 3 wk) home exercise (60% of VO2max 20-30 min, 7 sessions per week, 12 wk) + 1 supervised session ( 60 min, walking, calisthenics, ball games); Control group: No intervention	12 wk	↑ EPC levels		[115]
Male	37	Exercise (n = 15) 65 ± 7 yr old; CHF control (n = 15) 63 ± 7 yr old; Healthy control (n = 7) 66 ± 4 yr old	NYHA functional class II	Aerobic	Exercise group: Bicycle ergometer HR of ventilatory threshold 30 min 5 sessions per week; Control groups: No intervention	3 mo	Exercise group ↑ EPC levels; Control patient group no change		[116]
Male (n = 24); Female (n = 16)	40	Exercise (n = 30) 69 ± 8 yr old; Control (n = 20) 70 ± 11 yr old	PAD	Aerobic	Exercise group: Treadmill intermittent walking 5-10 min warm-up 35-50 min 2 sessions per week; Control group: No exercise intervention	6 mo	↑ EPC levels		[117]
Male (n = 22); Female (n = 18), median age 48 yr	40	Exercise (n = 40); Group A (n = 21) compliant individuals; Group B (n = 19) noncompliant individuals	Overweight and obese BMI ≥ 25 kg/m²	Aerobic	Non supervised self reported walking briskly or moderate running 45 min HR @ the individual anaerobic threshold 3 sessions per week	3 mo	Group A ↑ EPC levels; Group B no change	Small sample size; Limited duration of follow-up; Non valid compliance measurement; Unable to distinguish which (exercise or weight change) contributed to the increased EPC levels	[118]

EPC: Endothelial progenitor cell; BMI: Body mass index; NYHA: New York Heart Association; CHF: Chronic heart failure; CAC: Circulating angiogenic cell; PAD: Peripheral arterial disease.

Table 4 Acute effects of exercise in healthy subjects

Subjects	n	Study group; age (yr)	Modality	Exercise	Results	Limitations	Ref.
Men	22	Healthy 54 ± 10	Symptom limited exercise test	Treadmill/bicycle	↑ EPC + ↑ CAC		[120]
Men	16	Healthy 25.1 ± 2.7	Bruce modified	Treadmill	↑ EPC + ↑ NO level		[121]
Men (n = 2); Women (n = 9)	11	Healthy 31 ± 16	1 h Spinning session	Bicycle 80% HRmax	↑ OEC	No accurate peak VO2 measurements, no gender differentiation	[122]
Men	18	Healthy (sportive) 32.4 ± 2.3	Ergometer test	Bicycle 70% IAT 240 min	↑ EPC	No control	[123]
Men	23	Endurance athletes 62 ± 1.6; Healthy low active 65 ± 1.5	Exercise test	Treadmill 75% ± 5% VO2max 30 min (5 min ramp-up + 25 min + 3 min cool down)	No change in both groups, no change between groups		[124]
Men; Women	25	GroupI(n = 11) 23.9 ± 1.4; Group II (n = 14) 36.2 ± 9.3	Symptom limited cardiopulmonary exercise test	Bicycle ergometer: 40 W warm up; 20 W incremental test	↑ EPC	Small sample size	[125]
Men	25	Healthy	Running exercise	Protocol 1 30 min 100% IAT; Protocol 2 30 min 80% IAT; Protocol 3 10 min 80% IAT	Protocol 1 ↑ EPC; Protocol 2 ↑ EPC; Protocol 3 no change		[126]
Men	68	Marathon runners 57 ± 6	Marathon	Race	No change		[127]
Men	10	Marathon protocol (n = 9) 43.6 ± 11.6; Field test protocol (n = 8) 43.4 ± 10.9	Running exercise	Marathon protocol marathon race; Field test protocol 1500 m max speed	Marathon protocol no change; Field test protocol ↑ EPC		[128]
Men	20	Spartathlon runners (n = 10) 42.8 ± 1.4 Control sedentary (n = 10) 42.2 ± 10.4	Spartathlon	Exercise group race (246 km); Control group no intervention	Spartathlon runners ↑ EPC; Control no change		[129]

EPC: Endothelial progenitor cell; CAC: Circulating angiogenic cell; IAT: Individual anaerobic threshold.

Table 5 Acute effects of exercise in different disease populations

Subjects	n	Study group; age (yr)	Disease	Modality	Exercise prescription	Duration	Results	Ref.
Men	37	Young group (n = 9), mean age 33; Old group (n = 13), mean age 66; PAD group (n = 15), mean age 69	PAD	Treadmill	Young group bruce protocol; Old group gardner protocol; PAD group gardner protocol	Young group until exhaustion or 15 min; Old group 10 min; PAD group symptom limited or 10 min	Young group ↑ EPCs; Old group no change; PAD group no change	[130]
Male (n = 41); Female (n = 13)	54	Healthy controls (n = 13) 55.7 ± 1.6; Mild CHF (n = 22) 61.9 ± 2.5; Severe CHF (n = 19) 63 ± 2.6	CHF	Bicycle ergometer	Cardiopulmonary exercise testing individualized ramp protocol	8-10 min	EPC no change; Improved CAC migration in mild CHF + severe CHF	[131]
Male (n = 13); Female (n = 2)	15	Young group (n = 4) mean age 33; Old group (n = 4) mean age 66; CHF group (n = 7) mean age 69	CHF II/III	Bicycle ergometer	Symptom-limited graded exercise test		↑EPCs in young group; ↑EPCs in old group; Non significant ↑EPCs in CHF group	[132]

EPC: Endothelial progenitor cell; CHF: Chronic heart failure; CAC: Circulating angiogenic cell; PAD: Peripheral arterial disease.