title: Inflammation is associated with a reduced number   of pro-angiogenic Tie-2 monocytes and endothelial progenitor   cells in patients with critical limb ischemia.
abstract: BACKGROUND
  Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells.
  
  
  METHODS
  Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months.
  
  
  RESULTS
  In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01).
  
  
  CONCLUSIONS
  We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.
authors.forename: Jörn F
authors.initials: JF
authors.lastname: Dopheide
authors.forename: Philipp
authors.initials: P
authors.lastname: Geissler
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rubrech
authors.forename: Amelie
authors.initials: A
authors.lastname: Trumpp
authors.forename: Geraldine C
authors.initials: GC
authors.lastname: Zeller
authors.forename: Karsten
authors.initials: K
authors.lastname: Bock
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dorweiler
authors.forename: Friedrich
authors.initials: F
authors.lastname: Dünschede
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.forename: Christine
authors.initials: C
authors.lastname: Espinola-Klein
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000473:pathology*; D005121:Extremities / Q000098:blood supply* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D042787:Receptor, TIE-2 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2