Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD)

Abstract

IntroductionSepsis is characterized by systemic microvascular dysfunction. Endothelial progenitor cells (EPCs) are critically involved in maintaining vascular homeostasis under both physiological and pathological conditions. The aim of the present study was to analyze the endothelial progenitor cell system in patients suffering from sepsis with acute renal dysfunction.MethodsPatients with newly diagnosed sepsis were recruited from the ICU in a nonrandomized prospective manner. Blood samples were obtained within the first 12 hours after the diagnosis of sepsis. For quantifying endothelial progenitor cells (EPCs), CD133+/Flk-1+ cells were enumerated by cytometric analysis. Analysis of EPC proliferation was performed by a colony-forming units (CFU) assay. Blood concentrations of proangiogenic mediators were measured by ELISA. Acute renal dysfunction was diagnosed according to the Acute Kidney Injury Network (AKIN) criteria. Depending on the overall mean creatinine concentration during the stay at the ICU, patients were either assigned to a 'normal creatinine group' or to a 'high creatinine group'. Survival rates, frequency of dialysis, the simplified acute physiology score (SAPS) II scores, and different laboratory parameters were collected/used for further clinical characterizationResultsCirculating EPCs were significantly higher in all sepsis patients included in the study as opposed to healthy controls. Patients within the 'high creatinine group' showed an even more pronounced EPC increase. In contrast, EPC proliferation was severely affected in sepsis. Neither total circulating EPCs nor EPC proliferation differed between patients requiring dialysis and patients without renal replacement therapy. Cell numbers and cell proliferation also did not differ between surviving patients and patients with sepsis-related death. Serum levels of vascular endothelial growth factor (VEGF), stromal derived factor-1 (SDF-1), and Angiopoietin-2 were higher in sepsis than in healthy controls. Sepsis patients within the 'high creatinine group' showed significantly higher mean serum levels of uric acid.ConclusionsSepsis significantly affects the endothelial progenitor cell system, as reflected by increased EPC numbers, increased concentrations of proangiogenic mediators, and reduced proliferative capacity of the cells. This occurs independently from the frequency of dialysis and from patient survival. Increased serum levels of uric acid are possibly responsible for stronger EPC mobilization in sepsis patients with higher average creatinine levels.

Mobilization of Circulating Endothelial Progenitor Cells Correlates with the Clinical Course of Hantavirus Disease

“…We observed a 3-fold higher level of cEPCs in hantavirus disease patients than in the healthy control group. In septic patients, the number of cEPCs is 2 to 4 times that in healthy controls (31,32). The increase in cEPC numbers seems to indicate a mobilization of progenitor cells due to hantavirus-induced endothelial damage.…”

“…For example, multiple organ failure in sepsis is a consequence of altered endothelial function due to infection and the subsequent host response. Recently, several studies have identified the key role of EPCs in the outcome of severe sepsis (30)(31)(32). The number of cEPCs in septic patients correlates with survival and inversely with the severity of the clinical course.…”

Endothelial Progenitor Cells and a Stromal Cell–derived Factor-1α Analogue Synergistically Improve Survival in Sepsis

“…Recent studies have also shown that circulating EPCs are associated with human sepsis (9,10). In two studies, patients with sepsis were found to have increased numbers of circulating EPCs by flow cytometry compared with control subjects (10,34).…”

“…MiRNA-126, -34a, -155, and -125b expression in serum exosomes were determined by realtime PCR. Lung permeability was determined using Evans blue dye as previous described (30 EPCs in peripheral blood were determined as described (10). Cells were stained with the following antibodies: FITC-antimouse-CD34 antibody (eBioscience, San Diego, CA) and PE-antimouse-FLK-1 (BD Biosciences, San Diego, CA).…”

Therapeutic strategies in pneumonia: going beyond antibiotics

“…An increased number of circulating EPCs was detected in ARDS patients and correlated with improved survival [101]. However, in septic individuals endogenous EPCs showed reduced proliferative, adhesive, migratory and angiogenic capacities [102,103]. Experimentally, two different approaches were performed to maintain the beneficial effects of EPCs.…”