ABSTRACT
The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.
Subject(s)
Endothelial Progenitor Cells/pathology , Peripheral Arterial Disease/pathology , Aged , Ankle Brachial Index , Antigens, CD34/blood , Biomarkers/blood , Case-Control Studies , Cell Count , Cell Proliferation , Cell Separation/methods , Cells, Cultured , Colony-Forming Units Assay , Endothelial Progenitor Cells/chemistry , Female , Flow Cytometry , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/physiopathology , Predictive Value of Tests , Severity of Illness Index , Vascular Endothelial Growth Factor Receptor-2/bloodABSTRACT
BACKGROUND: Anti-Fy(a) has been implicated in hemolytic transfusion reactions. However, not all Fy(a-) patients develop anti-Fy(a) after transfusion with 1 unit of blood [Fy(a+)]. This study was designed to identify HLA-DRB1 alleles associated with a predisposition to Fy(a) immunization after blood transfusion. STUDY DESIGN AND METHODS: To identify HLA-DRB1 alleles prone to immunization after blood transfusion or pregnancy, HLA-DRB1 genotyping using polymerase chain reaction with sequence-specific oligonucleotide nonradioactive probe/sequence-specific priming methods was performed on blood samples from 67 immunized patients and 200 unrelated controls from the same southern European population in a case-control retrospective study. RESULTS: Ninety-six percent of patients with anti-Fy(a) had at least one HLA-DRB1 04 or HLA-DRB1 15 allele compared to 34% of controls (p(c) < 0.001). Furthermore HLA-DRB1 04 and HLA-DRB1 1501 frequencies were significantly increased in Fy(a)-immunized patients (35% vs. 12%, p(c) < 0.001; and 30% vs. 19%, p(c) < 0.001, respectively). Among HLA-DRB1 04 allelic subtypes, DRB1 0401 and DRB1 0403 alleles were more strongly correlated with Fy(a) immunization (51% vs. 24% and 19% vs. 9%; p(c) < 0.001, respectively). CONCLUSIONS: This study indicated that HLA-DRB1 04 and DRB1 1501 are overrepresented in Fy(a)-immunized patients. The correlation between these alleles and Fy(a) immunization could be due to a particular presentation of the Fy(a) peptide in HLA-DRB1 molecules.
