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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. Subjects EPCs (number/function) Findings Fadini et al [14 ] 55 diabetic without PAD 72 diabetic with PAD CD34+ /CD133+ /KDR+ CD34+ /CD133+ /KDR+ is significantly lower in diabetics with PAD compared to diabetics alone Fadini et al [15 ] 15 healthy controls 30 PAD CD34+ /KDR+ CD34+ /KDR+ is significantly lower in patients with PAD than controls Delva et al [17 ] 24 healthy controls 45 PAD CFU 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 PAD CD34+ /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. Subjects EPCs (number/function) Findings Vasa et al [18 ] 9 healthy controls CD34+ /KDR+ (flow cytometry) Both CD34+ /KDR+ and migratory activity were impaired in patients with CAD compared to controls 45 CAD Migratory activity Eizawa et al [19 ] 36 healthy controls CD34+ (flow cytometry) CD34+ is significantly decreased in patients with stable CAD 34 stable CAD Wang et al [20 ] 44 controls CD34+ /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 CAD Migratory activity 25 severe CAD Liguori et al [21 ] 15 healthy controls CFU CFU, CD34+ and migratory capacity were significantly impaired in patients with CHD CHD is the main predictor which impairs CFU capacity 40 CHD CD34+ (flow cytometry) Migratory activity Briguori et al [22 ] 136 CAD CFU Low levels of CFU and CD34+ /KDR+ predict CAD progression CD34+ /KDR+ (flow cytometry) Güven et al [23 ] 24 controls CD34+ (flow cytometry) CD34+ EPC is significantly elevated in CAD patients compared to controls 24 CAD EPCs is also positively correlated with maximum stenosis Werner et al [24 ] 90 CHD CFU CD34+ /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. Subjects EPCs (number/function) Findings Valgimigli et al [28 ] 45 healthy controls 91 CHF CD34+ , 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 CHF CD34+ (flow cytometry) CD34+ is significantly higher in mild CHF compared to severe CHF Michowitz et al [30 ] 107 CHF CFU CFU 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. Subjects Drugs Duration EPCs (number/function) Findings Angiotensin II receptor blockers Yao et al [33 ] 42 SHR-SP rats Losartan (10 mg/kg per day) vs Placebo 2 wk CFU CD34+ (flow cytometry) Migratory activity Losartan improved EPC number and function from SHR-SP rats compared to WKY rats Yu et al [34 ] 18 SHR-SP rats Candesartan (1 mg/kg per day) vs Tempol, Trichlormethiazide 2 wk CFU The highest CFU count was observed in candesartan treatment group Yoshida et al [35 ] 12 SHR-SP rats Valsartan (300 mg/L) vs Hydralazine 2 wk CFU Migratory activity Treatment with valsartan stimulated increase in CFU and migration activity in SHR-SP rats compared to hydralazine-treated rats Honda et al [36 ] 15 healthy controls Telmisartan (1 μmol/L) vs Valsartan 4 d CFU Proliferation activity CFU and EPC proliferative activity are significantly increased in cells treated with telmisartan in vitro Pelliccia et al [37 ] 40 CAD Telmisartan (80 mg/d) vs Placebo 4 wk CD34+ /CD45- / KDR+ (flow cytometry) CD34+ /CD45- /KDR+ is significantly elevated in patients treated with telmisartan Angiotensin converting enzyme inhibitors Min et al [39 ] 20 CAD Ramipril (5 mg/d) vs Placebo 4 wk EPC number Migratory activity Proliferation activity Adhesion activity There 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 HT Enalapril (20 mg/d) vs Zofenopril (30 mg/d) 1 yr and 5 yr CFU Migratory activity Increased 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 HT Nifedipine (20 mg/d) vs Untreated 4 wk CD34+ /CD133+ (flow cytometry) Migratory activity EPC number and function were significantly improved in the nifedipine group de Ciuceis et al [44 ] 29 essential HT Barnidipine (20 mg/d) vs Hydrochlorothiazide (25 mg/d) 3 and 6 mo EPC number EPC 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. Subjects Drugs Duration EPCs (number/function) Findings Vasa et al [46 ] 15 CAD Atorvastatin (40 mg/d) 4 wk CD34+ /KDR+ (flow cytometry) Migratory activity CD34+ /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 STEMI Atorvastatin (80 mg/d) vs Atorvastatin (20 mg/d) 16 wk CD34+ /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 CAD Atorvastatin (20 mg/d) vs Placebo 3 wk CD34+ /CD133+ (flow cytometry) Atorvastatin has significantly elevated EPC count after 3 wk Erbs et al [49 ] 42 CHF Rosuvastatin (40 mg/d) vs Placebo 12 wk CD34+ /KDR+ (flow cytometry) Rosuvastatin significantly increased EPC count compared to placebo Tousoulis et al [50 ] 60 SHF Rosuvastatin (10 mg/d) vs Allopurinol (300 mg/d) 4 wk CD34+ /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 ICM Atorvastatin (10 mg/d) vs Atorvastatin (40 mg/d) 1 yr CD34+ (flow cytometry) CD34+ count was significantly elevated in patients under 40 mg atorvastatin after 1 yr Paradisi et al [52 ] 20 healthy controls Pravastatin (40 mg/d) vs Placebo 8 wk CFU Tubule formation assay CFU 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 Untreated 8 wk CFU 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. Subjects Drugs Duration EPCs (number/function) Findings Thiazolidinedione/metformin Wang et al [54 ] 36 type 2 diabetes Metformin + Pioglitazone (30 mg/d) (n = 24) vs Metformin (n = 12) 8 wk CD34+ /KDR+ (flow cytometry) Migratory activity Both EPC number and migration activity improved with combination of metformin and pioglitazone Werner et al [55 ] 54 CAD Pioglitazone (45 mg/d) vs Placebo 4 wk CFU CD34+ (flow cytometry) Improved EPC number and CFU count with pioglitazone treatment Makino et al [56 ] 34 type 2 diabetes Pioglitazone (15-30 mg/d) 24 wk CD34+ (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 diabetes Pioglitazone (15-45 mg/d) (n = 55) vs Metformin (1000-2000 mg/d) (n = 55) 24 wk CD34+ /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 diabetes Metformin (1700-2550 mg/d) 16 wk CD45- /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 diabetes Sitagliptin (100 mg/d) (n = 16) vs Metformin (n = 16) 4 wk CD34+ /KDR+ (flow cytometry) EPC number in sitagliptin group significantly improved compared to metformin group by 2 fold