4.
Clinical studies illustrating changes in blood levels of EPC in cardiovascular situations
| Disease/condition | Methods for EPC detection | Main finding(s) | Ref | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FCM | Culture assay | ||||||||||||
| Panel A : Disease/condition associated with increased EPC levels | |||||||||||||
| Acute ischemia | |||||||||||||
| Myocardial infarction | CD34+/CD117+, CD34+/KDR+ | EPC correlated plasma VEGF levels and CPK values | [94] | ||||||||||
| CD133+/KDR+ | + | EPC correlated with collateral vessel formation | [95] | ||||||||||
| CD34+/CD133+/KDR+ | + | EPC differentiation is associated with myocardial salvage | [96] | ||||||||||
| CD34+ | EPC mobilization correlated with favourable post-AMI remodelling | [97] | |||||||||||
| Unstable angina | + | Correlation with serum CRP levels | [98] | ||||||||||
| Stroke | + | EPC increment in the first week is associated with good outcome | [99] | ||||||||||
| CD31+/CD34+, CD34+/KDR+ | EPC mobilization predicted improvement of neurological outcome | [100] | |||||||||||
| Liver transplantation | CD34+/CD133+, CD34+/KDR+ | Host derived cells, associated with VEGF, SCF, G-CSF increase | [101] | ||||||||||
| Coroanary artery bypass grafting | + | EPC mobilization correlated with G-CSF levels | [102] | ||||||||||
| CD34+/CD133+ | EPC increase is associated with cytochemokine release and showed a negative age dependency | [103] | |||||||||||
| Vascular injury | |||||||||||||
| Coronary stent implantation | CD34+ | + | EPC increase is more marked in patients developing restenosis | [104] | |||||||||
| CD34+/CD45low | + | EPC mobilization inversely correlated with vascular injury assessed by CEC count | [105] | ||||||||||
| Drugs/Life style modifications | |||||||||||||
| Statins therapy | CD34+/CD133+/KDR+ | + | EPC increase in independent of VEGF | [106] | |||||||||
| CD45−/KDR+ | + (early and late EPC) | EPC increase is associated with enhanced EPC function in relation to IL-8 production by monocytes | [107] | ||||||||||
| + | In patients with chronic heart failure, EPC increase is associated with improvement of endothelial function (FMD) | [108] | |||||||||||
| CD34+/KDR+ | + (late EPC) | Long-term treatment in CAD patients | [109] | ||||||||||
| Erythropoletin | CD34+ | + | Standard EPO dose in patients with renal anaemia, increased EPC number is associated with increased EPC survival and function | [110] | |||||||||
| CD34+/CD45− | + | One bolus of EPO in patients with acute myocardial infarction | [111] | ||||||||||
| Physical training | CD34+/CD133+/KDR+ | EPC increase correlated with FMD change | [112] | ||||||||||
| + | EPC increase is associated with intensified school sports in children | [113] | |||||||||||
| CD34+/KDR+ | + | EPC increase is associated with reduced EPC apoptosis in CAD patients | [114] | ||||||||||
| Panel B: Disease/condition associated with decreased EPC levels | |||||||||||||
| Cardiovascular diseases | |||||||||||||
| Stable CAD | CD34+/KDR+ | EPC number inversely correlates with the presence of CVRF | [117] | ||||||||||
| CD34+/KDR+ | Low levels of EPC independently predict poor prognosis | [118] | |||||||||||
| CD133+/KDR+ | + | EPC number and migratory activity inversely correlate with the severity of coronary stenosis and CRP | [119] | ||||||||||
| Cerebrovascular disease | CD34+, CD133+ | EPC level correlates with regional blood flow | [120] | ||||||||||
| Pulmonary hypertension | CD133+/KDR+ | + | EPC reduction correlates with IL-6, vWF and BNP levels and is associated with impaired migration and adhesion to fibronectin | [121] | |||||||||
| CD34+/C133+/KDR+ CD34+, CD34+/KDR+, CD34+/CD133+ | EPC reduction is associated with raised inflammatory markers and meliorated by phosphodiesterase inhibitor Sildenafil | [122] | |||||||||||
| Heart failure | CD34+ | EPC inversely correlate with disease severity | [123] | ||||||||||
| CD34+ CD133+/KDR+ | + | EPC reduction is associated with functional exhaustion of EPC within bone marrow | [124] | ||||||||||
| + | EPC reduction is associated with the advances phases of the disease | [125] | |||||||||||
| In-stent restenos | + | Low EPC number and function is associated with diffuse restenosis | [126] | ||||||||||
| + | Increased EPC senescence is associated with in-stent restenosis | [127] | |||||||||||
| Cardiovascular risk factors | |||||||||||||
| Type 2 Diabetes | CD34+/CD117+, | EPC number negatively correlated with disease severity, and individually predict microvascular complications, | [128] | ||||||||||
| CD34+/CD133+/KDR | + | EPC reduction is associated with EPC dysfunction involving eNOS | [129] | ||||||||||
| + | EPC number is related to HbA1c levels in untreated patients and increased by pharmacological glycemic control | [130] | |||||||||||
| CD34+/KDR+ | EPC reduction is more marked in patients with peripheral vascular disease, EPC number correlates with ABI | [131] | |||||||||||
| Type 1 Diabetes | + | Low EPC number is associated with EPC dysfunction | [132] | ||||||||||
| Hypertension | CD34+/KDR+ | EPC inversely correlates with systolic blood pressure | [133] | ||||||||||
| CD34+/CD133+/CD45 | Refractory hypertension independantly determines EPC number | [134] | |||||||||||
| End stage renal disease | CD34+/KDR+ | + | EPC reduction and altered function are related to serum fetuin A levels, haematocrite and reticulocytes | [135] | |||||||||
| CD34+/CD144+ | + | EPC number and migration inversely correlates with uraemia and systolic blood pressure and is restored by nocturnal haemodialysis | [136] | ||||||||||
| CD34+/KDR+ | + | Uremic serum impaired normal EPC outgrown in vitro | [137] | ||||||||||
| CD34+/CD45+ | + | EPC number correlated with renal function and is normalized after renal transplantation | [138] | ||||||||||
| + | EPC Inversely correlates with framingham score and dose of dialysis | [139] | |||||||||||
| Dyslipidemia | + | EPC number and impaired functionality Inversely correlated with total and LDL cholesterol | [140] | ||||||||||
| CD34+/KDR+ | EMP/EPC Ratio correlates with LDL cholesterol and arterial stiffness | [141] | |||||||||||
| Smoking | + | Impaired EPC function related to increased oxidative stress | [142] | ||||||||||
| CD34+/CD133+/KDR+ | + | EPC levels increased after 2 week smoking cessation | [143] | ||||||||||
| aging | CD34+ CD34+/KDR+ | + | EPC reduction correlated with decreased arterial elasticity | [144] | |||||||||
| Increased EPC levels is childhood, inverse relation with age in healthy individuals | [145] | ||||||||||||
| Hyperhomocysteinemia | CD133+/KDR+ | + | EPC levels inversely correlated with Homocystein levels | [146] | |||||||||
Abbreviations : CAD, coronary artery disease, FMD, flow mediated dilatation, EPO, erythropïetin, CPK, creatine phosphokinase, AMI, acute myocar-dial infarction, CRP, C reactive protein, IL-8 : interleukin-8, VEGF, vascular endothelial growth factor, SCF, stem cell factor, G-SCF, granulocyte-stem cell factor, IL-6: interleukin-6, vWF, von Willebrant factor, BNP, type B natriuretic peptide; eNOs, endothelial Nitric oxide synthase, ABI, ankle brachial index, LDL, low-density lipoprotein.