title: Circulating Endothelial Cells Expressing the Angiogenic Transcription Factor Krüppel-Like Factor 4 are Decreased in Patients with Coronary Artery Disease.
abstract: OBJECTIVE
  The zinc finger transcription factor KLF4 is known to control diverse EC functions.
  
  
  METHODS
  The functional role of KLF4 for angiogenesis and its association with CAD was examined in HUVECs and human CECs.
  
  
  RESULTS
  In two different angiogenesis assays, siRNA-mediated KLF4 downregulation impaired HUVEC sprouting and network formation. Conversely, KLF4 overexpression increased HUVEC sprouting and network formation. Similar findings were observed after incubation of HUVECs with CdM from KLF4 cDNA-transfected cells, suggesting a role of paracrine factors for mediating angiogenic KLF4 effects. In this regard, VEGF expression was increased in KLF4-overexpressing HUVECs, whereas its expression was reduced in HUVECs transfected with KLF4 siRNA. To examine the relevance of our in vitro findings for human endothelial dysfunction, we analyzed the expression of KLF4 in CECs of patients with stable CAD. Flow cytometry analyses revealed decreased numbers of KLF4-positive CECs in peripheral blood from CAD patients compared to healthy controls.
  
  
  CONCLUSIONS
  Our findings suggest that KLF4 may represent a potential biomarker for EC dysfunction. In the future, (therapeutic) modulation of KLF4 may be useful in regulating EC function during vascular disease processes.
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Frauke S
authors.initials: FS
authors.lastname: Czepluch
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.|Institute of Cardiovascular Physiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Vogler
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Kuschicke
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Meier
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Rajinikanth
authors.initials: R
authors.lastname: Gogiraju
authors.affiliation: Institute of Cardiovascular Physiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Dörthe M
authors.initials: DM
authors.lastname: Katschinski
authors.affiliation: Department of Transfusion Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Riggert
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.|Medical Clinic 2, Department of Cardiology, University Medical Center Mainz, Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
mesh_terms: D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000097:blood* / Q000235:genetics; D008297:Male
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
keywords: Krüppel-like factor 4; angiogenesis; coronary artery disease; endothelial cells; vascular endothelial growth factor