title: Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction.
abstract: BACKGROUND
  Chronic heart failure (HF) remains a leading cause of cardiovascular (CV) mortality and morbidity worldwide. The aim of the study was to investigate whether the pattern of angiogenic endothelial progenitor cells (EPCs) and apoptotic endothelial cell-derived microparticles (EMPs) would be able to differentiate HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction.
  
  
  METHODS
  One hundred sixty four chronic HF subjects met inclusion criteria. Patients with global left ventricular ejection fraction ≥ 50% were categorized as the HFpEF group (n = 79) and those with ≤ 45% as the HFrEF group (n = 85). Therefore, to compare the circulating levels of biological markers 35 control subjects without HF were included in the study. All control individuals were age- and sex-matched chronic HF patients. The serum level of biomarkers was measured at baseline. The flow cytometric technique was used for predictably distinguishing circulating cell subsets depending on expression of CD45, CD34, CD14, Tie-2, and CD309 antigens and determining endothelial cell-derived microparticles. CD31(+)/annexin V(+) was defined as apoptotic endothelial cell-derived MPs, MPs labeled for CD105(+) or CD62E(+) were determined as MPs produced due to activation of endothelial cells.
  
  
  RESULTS
  In multivariate logistic regression model T2DM (R(2) = 0.26; P = 0.001), obesity (R(2) = 0.22; P = 0.001), previous MI (R(2) = 0.17; P = 0.012), galectin-3 (R(2) = 0.67; P = 0.012), CD31(+)/annexin V(+) EMPs (R(2) = 0.11; P = 0.001), NT-proBNP (R(2) = 0.11; P = 0.046), CD14(+) CD309(+) cells (R(2) = 0.058; P = 0.001), and CD14(+) СD309(+) Tie-2(+) cells (R(2) = 0.044; P = 0.028) were found as independent predictors of HFpEF. Using multivariate Cox-regression analysis adjusted etiology (previous myocardial infarction), cardiovascular risk factors (obesity, type 2 diabetes mellitus) we found that NT-proBNP (OR 1.08; 95% CI = 1.03-1.12; P = 0.001) and CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio (OR 1.06; 95% CI = 1.02-1.11; P = 0.02) were independent predictors for HFpEF.
  
  
  CONCLUSIONS
  We found that CD31(+)/annexin V(+) EMPs to CD14(+) CD309(+) cell ratio added to NT-proBNP, clinical data, and cardiovascular risk factors has exhibited the best discriminate value and higher reliability to predict HFpEF compared with NT-proBNP and clinical data/cardiovascular risk factors alone.
authors.affiliation: Internal Medicine Department, State Medical University of Zaporozhye, 26, Mayakovsky av., Zaporozhye UA-69035, Ukraine.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Berezin
authors.affiliation: Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kremzer
authors.affiliation: Pathology and Immunology Department, Clinical Laboratory "Dia-Service", Zaporozhye, Ukraine.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Martovitskaya
authors.affiliation: Private Medical Center "Vita-center", Zaporozhye, Ukraine.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Berezina
authors.affiliation: Pathology Bureau, Zaporozhye, Ukraine.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Gromenko
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Chronic heart failure; Endothelial cell-derived microvesicles; Endothelial progenitor cells; Preserved left ventricular function