Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke

Abstract

IntroductionErythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.MethodsIn total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or serve as placebo (group 2). The circulating level of EPCs (double-stained markers: CD31/CD34 (E1), CD62E/CD34 (E2) and KDR/CD34 (E3)) was determined using flow cytometry at 48 h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.ResultsCirculating EPC (E1 to E3) level at 48 h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48 h and on Day 7 after IS, EPC (E1 to E3) level did not differ between groups 1 and 2 (all P > 0.1). However, by Day 21, EPC (E1 to E3) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy (95% confidence interval (CI), 0.153 to 0.730; P = 0.006) and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) levels were significantly and independently predictive of a reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale ≥8, or death).ConclusionsEPO therapy significantly improved circulating EPC level and 90-day MANE.Trial registration numberISRCTN: ISRCTN96340690

Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

“…More specifically, the adventitial resident VPCs play a major role in the repair of the injured endothelium via migration toward the endothelium and differentiation into an EC lineage 5, 6…”

“…Dysfunction of endothelial cells (ECs) is thought to play a pivotal role in injured endothelium, and EC health has been suggested to be maintained by a consistent supply of supporting growth factors and activation of local stem/progenitor cells that are capable of differentiation toward ECs 3, 4. It is well documented that vascular progenitor cells (VPCs), which are mainly located in the adventitia, contribute to the repair of the injured endothelium via migration toward the endothelium and differentiation into an EC lineage 5, 6. These VPCs are also an important source for the regeneration of tissue‐engineered vascular grafts 7, 8…”

High-Density Lipoproteins in Stroke

“…In rats, EPCs injected 24 h after tMCAO were shown to reach the injured area and improved functional recovery, potentially attributable to antiapoptotic factors secreted by EPCs (Moubarik et al 2011). In humans, erythropoietin therapy significantly increased the number of circulating EPCs and improved a 90-day major adverse neurological effect (Yip et al 2011). Different studies report that reconstituted HDLs may increase circulating EPC number (Tso et al 2006) and their differentiation from mononuclear cells as well as their angiogenic capacity (Sumi et al 2007).…”

Levels of Circulating Neopterin in Patients with Severe Carotid Artery Stenosis Undergoing Carotid Stenting

“…The patients consisted of some of the disease-control subjects in another recently reported study 29) . In these patients, AIS was defined as the sudden onset of the loss of the global or focal cerebral function persisting for more than 24 hours.…”

“…In these patients, AIS was defined as the sudden onset of the loss of the global or focal cerebral function persisting for more than 24 hours. The radiological criteria for a diagnosis of AIS included a new finding of low attenuation density in focal or diffuse brain areas on computed tomography of the brain or the appearance of area(s) of high intensity (bright spots) on diffusion-weighted image (DWI) magnetic resonance imaging (MRI) or low intensity on apparent diffusion coefficient (ADC) value MRI 29) [29]. Additionally, the serum levels of neopterin were measured in 33 age-and gender-matched control subjects.…”