Table 2.
Key players involved in modulating circulating EPC levels and functions.
| Factors | Effects | References |
|---|---|---|
| Factors and conditions associated with altered circulating EPCs levels | ||
| Aging | It determines a decrease in progenitor cells activity and mobilization | [26, 27] |
| Inflammation | Restricted acute inflammatory response stimulates EPCs mobilization while persistent chronic inflammatory stimuli have deleterious effects and result in decreased number of circulating mature and functional EPCs C-reactive protein (CRP) exerts direct inhibitory effects on EPC differentiation and survival. Proinflammatory TNF-α reduces EPCs number |
[28, 29] |
| Oxidative stress | It reduces EPCs number, induces apoptosis, and reduces EPCs capacity of mobilization, migrating, and incorporating into vasculature | [28, 29] |
| Hypothyroidism | It decreases CD34+/CD133+/KDR+ EPCs | [31, 32] |
| Cardiovascular risk factors (smoking, diabetes, hypertension, lipid disorders, abdominal obesity, metabolic syndrome, etc.) | They influence the circulating levels of EPCs; precisely they reduce their levels | [30] |
| Hyperparathyroidism | It increases circulating EPCs levels | [31, 32] |
|
| ||
| Physiological factors involved in EPCs mobilization | ||
| Gender | It upregulates VEGF and SDF-1 It modulates EPCs levels and cardiovascular risk profile, due to the beneficial effects of estrogens particularly in women The increase seems to be related to oestrogens levels |
[33] |
| Pregnancy | It increases EPCs-derived colonies | [34] |
|
| ||
| Drug therapies modulating circulating EPCs levels | ||
| Antihypertensive drugs | [35] | |
| Calcium channel blockers (CCBs) nifedipine and barnidipine | They enhance EPC number and function | |
| Angiotensin II receptor blocker (ARB) telmisartan | It enhances EPC number and function | |
| Angiotensin converting enzyme (ACE) inhibitors | They improves clonogenic capacity | [35] |
| Cholesterol lowering medications | ||
| Statines (atorvastatin, rosuvastatin) | They increase mobilization of EPCs and CD34+/CD117+, CD34+/CXCR4+ | [35] |
| Antidiabetic medications | ||
| Oral dipeptidyl peptidase-4 inhibitor (sitagliptin) | It increases number of circulating EPCs in patients with diabetes | [35] |
| Thiazolidinedione/metformin | They improve EPCs number and function | |
| Other drugs | ||
| Estradiol | It improves capacity of neovascularization | [26] |
| PPAR-γ agonist | It increases EPCs migration | [26] |
| CXCR4 agonists | They stimulate SC mobilization | [26] |
| AMD3100 (plerixafor) | It increases CD34+, CD117+, and CD133+ cells | |
| POL6326 | ||
| Erythropoietin | It increases EPC and HSC levels | [24] |
| Nitroglycerin (chronic use) | It increases apoptosis and decreases phenotypic differentiation and migration | [26] |
| Granulocytes colony stimulating factor (G-CSF) | It induces SC mobilization by interruption of CXCR4/CXCL12, c-Kit/SCF, and VLA-4/VCAM-1 axis | [26] |
| Growth hormone | It reduces apoptosis | [26] |
| It improves EPCs migratory capacity | ||
|
| ||
| Lifestyle modification and nutritional interventions | ||
| Red wine resveratrol, salvianolic acids, Gingko Biloba, ginsenoside, berberine, and puerarine. | They exert anti-inflammatory and antioxidant effects They enhance EPCs activity |
[26] |
| Diet | It affects the number of circulating EPCs | [36, 37] |
| Dietary cocoa-derived flavonoids | They increase number of functional circulating angiogenic cells | [26] |
| Red ginseng extracts | They increase EPCs number | [26] |
| Physical exercise | It improves circulating EPCs levels. Prolonged 4-week exercise program improves EPCs functions. Maximal and endurance exercise influence the number of both EPCs and hematopoietic stem cells. | [26] |