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Copyright ©2014 Baishideng Publishing Group Inc.
World J Stem Cells. Jul 26, 2014; 6(3): 355-366
Published online Jul 26, 2014. doi: 10.4252/wjsc.v6.i3.355
Table 1 Effect of peripheral arterial disease on endothelial progenitor cells
Ref.SubjectsEPCs (number/function)Findings
Fadini et al[14]55 diabetic without PAD 72 diabetic with PADCD34+/CD133+/KDR+CD34+/CD133+/KDR+ is significantly lower in diabetics with PAD compared to diabetics alone
Fadini et al[15]15 healthy controls 30 PADCD34+/KDR+CD34+/KDR+ is significantly lower in patients with PAD than controls
Delva et al[17]24 healthy controls 45 PADCFU CD133+, CD34+, CD34+/KDR+CFU is significantly increased in patients with PAD compared to controls CD34+ and CD133+ are significantly decreased in patients with PAD compared to controls No difference between groups for CD34+/KDR+
Morishita et al[16]22 healthy controls 48 PADCD34+/CD133+/ KDR+CD34+/CD133+/KDR+ is significantly higher in PAD compared to controls
Table 2 Effect of coronary artery disease on endothelial progenitor cells
Ref.SubjectsEPCs (number/function)Findings
Vasa et al[18]9 healthy controlsCD34+/KDR+ (flow cytometry)Both CD34+/KDR+ and migratory activity were impaired in patients with CAD compared to controls
45 CADMigratory activity
Eizawa et al[19]36 healthy controlsCD34+ (flow cytometry)CD34+ is significantly decreased in patients with stable CAD
34 stable CAD
Wang et al[20]44 controlsCD34+/KDR+ (flow cytometry)CD34+/KDR+ is the lowest in severe CAD followed by mild CAD Migratory activity is also impaired in CAD patients
35 mild CADMigratory activity
25 severe CAD
Liguori et al[21]15 healthy controlsCFUCFU, CD34+ and migratory capacity were significantly impaired in patients with CHD CHD is the main predictor which impairs CFU capacity
40 CHDCD34+ (flow cytometry)
Migratory activity
Briguori et al[22]136 CADCFULow levels of CFU and CD34+/KDR+ predict CAD progression
CD34+/KDR+ (flow cytometry)
Güven et al[23]24 controlsCD34+ (flow cytometry)CD34+ EPC is significantly elevated in CAD patients compared to controls
24 CADEPCs is also positively correlated with maximum stenosis
Werner et al[24]90 CHDCFUCD34+/KDR+ and CFU positively correlate with endothelium-dependent vasodilation (acetylcholine infusion)
CD34+/KDR+ (flow cytometry)
Table 3 Summary of clinical trials: Effect of heart failure on endothelial progenitor cells
Ref.SubjectsEPCs (number/function)Findings
Valgimigli et al[28]45 healthy controls 91 CHFCD34+, CD34+/CD133+/KDR+ (flow cytometry)CD34+ and CD34+/CD133+/KDR+ are significantly elevated in CHF patients compared to controls EPC number is negatively correlated with NYHA functional class
Nonaka-Sarukawa et al[29]22 healthy controls 16 mild CHF 10 severe CHFCD34+ (flow cytometry)CD34+ is significantly higher in mild CHF compared to severe CHF
Michowitz et al[30]107 CHFCFUCFU is the independent predictor for CHF CFU is also negatively correlated with NYHA functional class
Table 4 Effect of antihypertensive medications on endothelial progenitor cells
Ref.SubjectsDrugsDurationEPCs (number/function)Findings
Angiotensin II receptor blockers
Yao et al[33]42 SHR-SP ratsLosartan (10 mg/kg per day) vs Placebo2 wkCFU CD34+ (flow cytometry) Migratory activityLosartan improved EPC number and function from SHR-SP rats compared to WKY rats
Yu et al[34]18 SHR-SP ratsCandesartan (1 mg/kg per day) vs Tempol, Trichlormethiazide2 wkCFUThe highest CFU count was observed in candesartan treatment group
Yoshida et al[35]12 SHR-SP ratsValsartan (300 mg/L) vs Hydralazine2 wkCFU Migratory activityTreatment with valsartan stimulated increase in CFU and migration activity in SHR-SP rats compared to hydralazine-treated rats
Honda et al[36]15 healthy controlsTelmisartan (1 μmol/L) vs Valsartan4 dCFU Proliferation activityCFU and EPC proliferative activity are significantly increased in cells treated with telmisartan in vitro
Pelliccia et al[37]40 CADTelmisartan (80 mg/d) vs Placebo4 wkCD34+/CD45-/ KDR+ (flow cytometry)CD34+/CD45-/KDR+ is significantly elevated in patients treated with telmisartan
Angiotensin converting enzyme inhibitors
Min et al[39]20 CADRamipril (5 mg/d) vs Placebo4 wkEPC number Migratory activity Proliferation activity Adhesion activityThere was 1.5 fold increase in EPC number after 1 wk of treatment Followed by 2.5 fold increase in EPC count after 4 wk Migration, proliferation and adhesion activities were also significantly improved with ramipril
Cacciatore et al[40]36 HTEnalapril (20 mg/d) vs Zofenopril (30 mg/d)1 yr and 5 yrCFU Migratory activityIncreased CFU count for both treatment groups at 1 yr and 5 yr No difference for migratory activity
Calcium channel blockers
Sugiura et al[43]37 HTNifedipine (20 mg/d) vs Untreated4 wkCD34+/CD133+ (flow cytometry) Migratory activityEPC number and function were significantly improved in the nifedipine group
de Ciuceis et al[44]29 essential HTBarnidipine (20 mg/d) vs Hydrochlorothiazide (25 mg/d)3 and 6 moEPC numberEPC number was significantly elevated in patients treated with barnidipine compared to hydrochlorothiazide
Table 5 Effect of HMG-CoA reductase inhibitors (statins) on endothelial progenitor cells
Ref.SubjectsDrugsDurationEPCs (number/function)Findings
Vasa et al[46]15 CADAtorvastatin (40 mg/d)4 wkCD34+/KDR+ (flow cytometry) Migratory activityCD34+/KDR+ was significantly increased after 4 wk of therapy Migration activity was also significantly improved after 4 wk of treatment
Leone et al[47]40 STEMIAtorvastatin (80 mg/d) vs Atorvastatin (20 mg/d)16 wkCD34+/KDR+ (flow cytometry)Patients who took 80 mg of atorvastatin had higher CD34+/KDR+ than those who took 20 mg atorvastatin
Spadaccio et al[48]50 CADAtorvastatin (20 mg/d) vs Placebo3 wkCD34+/CD133+ (flow cytometry)Atorvastatin has significantly elevated EPC count after 3 wk
Erbs et al[49]42 CHFRosuvastatin (40 mg/d) vs Placebo12 wkCD34+/KDR+ (flow cytometry)Rosuvastatin significantly increased EPC count compared to placebo
Tousoulis et al[50]60 SHFRosuvastatin (10 mg/d) vs Allopurinol (300 mg/d)4 wkCD34+/KDR+, CD34+/CD133+/KDR+ (flow cytometry)CD34+/KDR+ and CD34+/CD133+/KDR+ are improved with rosuvastatin treatment compared to allopurinol
Huang et al[51]100 healthy controls 100 ICMAtorvastatin (10 mg/d) vs Atorvastatin (40 mg/d)1 yrCD34+ (flow cytometry)CD34+ count was significantly elevated in patients under 40 mg atorvastatin after 1 yr
Paradisi et al[52]20 healthy controlsPravastatin (40 mg/d) vs Placebo8 wkCFU Tubule formation assayCFU was increased by 31% in pravastatin group compared to placebo No difference was observed for tubule formation assay between groups
Hristov et al[53]209 CAD (without statin, n = 65, statin 10/20 mg/d, n = 101, statin 40 mg/d, n = 43)Statin (10/20 mg/d) or 40 mg/d vs Untreated8 wkCFU CD34+/KDR+ (flow cytometry)40 mg/d of statin treatment has significantly decreased EPC numbers Continuous statin therapy inversely correlated with EPC numbers
Table 6 Effect of anti-diabetic medications on endothelial progenitor cells
Ref.SubjectsDrugsDurationEPCs (number/function)Findings
Thiazolidinedione/metformin
Wang et al[54]36 type 2 diabetesMetformin + Pioglitazone (30 mg/d) (n = 24) vs Metformin (n = 12)8 wkCD34+/KDR+ (flow cytometry) Migratory activityBoth EPC number and migration activity improved with combination of metformin and pioglitazone
Werner et al[55]54 CADPioglitazone (45 mg/d) vs Placebo4 wkCFU CD34+ (flow cytometry)Improved EPC number and CFU count with pioglitazone treatment
Makino et al[56]34 type 2 diabetesPioglitazone (15-30 mg/d)24 wkCD34+ (flow cytometry)Number of CD34+ increased steadily at 12 wk and continued to increase after 24 wk of pioglitazone
Esposito et al[57]110 type 2 diabetesPioglitazone (15-45 mg/d) (n = 55) vs Metformin (1000-2000 mg/d) (n = 55)24 wkCD34+/KDR+ (flow cytometry)Significant improvement in CD34+/KDR+ in patients who took pioglitazone compared to metformin
Liao et al[58]51 healthy controls 46 type 2 diabetesMetformin (1700-2550 mg/d)16 wkCD45-/CD34+/KDR+ (flow cytometry)EPC number is significantly lower in type 2 diabetic patients and significantly improved after metformin
Dipeptidyl peptidase 4 inhibitors
Fadini et al[59]32 type 2 diabetesSitagliptin (100 mg/d) (n = 16) vs Metformin (n = 16)4 wkCD34+/KDR+ (flow cytometry)EPC number in sitagliptin group significantly improved compared to metformin group by 2 fold