PMID- 17968939
OWN - NLM
STAT- MEDLINE
DCOM- 20071219
LR  - 20071126
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 56
IP  - 11
DP  - 2007 Nov
TI  - Vascular endothelial damage and repair in antineutrophil cytoplasmic 
      antibody-associated vasculitis.
PG  - 3847-53
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is 
      characterized by necrotizing vessel wall inflammation, paralleled by the 
      detachment of endothelial cells. The repair of such endothelial defects is 
      crucial for the maintenance of regular structure and function of the injured 
      vessels. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to 
      play a pivotal role in the regeneration of damaged endothelium. The aim of this 
      study was to investigate whether EPCs are involved in vascular repair in AAV. 
      METHODS: We assessed disease activity, CD34+ hematopoietic progenitor cells 
      (HPCs) using flow cytometry, EPCs using an in vitro assay, and circulating 
      endothelial cells (CECs) by immunomagnetic isolation from the peripheral blood of 
      31 patients with active AAV at 1, 3, and 6 months after the initiation of 
      immunosuppressive therapy. RESULTS: In patients with untreated active disease, 
      HPC and EPC numbers were comparable with those in healthy control subjects (n = 
      64). With the induction of remission, the number of HPCs and EPCs increased 
      significantly, from a median of 1.5 cells/microl (range 0.0-7.0) to a median of 
      3.2 cells/microl (range 0.76-9.2) (P < 0.001) and from a median of 261 
      cells/high-power field (range 171-643) to a median of 470 cells/high-power field 
      (range 168-996) (P < 0.021), respectively. In contrast, the initially elevated 
      number of CECs decreased significantly (P < 0.001). We observed no correlation 
      between the number of HPCs or EPCs and the leukocyte count, the thrombocyte 
      count, or kidney function. CONCLUSION: In patients with AAV, the numbers of 
      circulating CD34+ HPCs and EPCs increased significantly after the institution of 
      immunosuppressive therapy and disease remission. This finding points to a role of 
      circulating CD34+ HPCs and EPCs in endothelial repair in vasculitis. Targeted 
      stimulation of these cells might represent a new possibility of improving 
      vascular healing in AAV.
FAU - de Groot, K
AU  - de Groot K
AD  - Hannover Medical School, Hannover, Germany. kirsten@de-groot.de
FAU - Goldberg, C
AU  - Goldberg C
FAU - Bahlmann, F H
AU  - Bahlmann FH
FAU - Woywodt, A
AU  - Woywodt A
FAU - Haller, H
AU  - Haller H
FAU - Fliser, D
AU  - Fliser D
FAU - Haubitz, M
AU  - Haubitz M
LA  - eng
PT  - Controlled Clinical Trial
PT  - Journal Article
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Antigens, CD34)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Antibodies, Antineutrophil Cytoplasmic/*immunology
MH  - Antigens, CD34/metabolism
MH  - Endothelial Cells/immunology/pathology
MH  - Endothelium, Vascular/*immunology/*pathology
MH  - Female
MH  - Flow Cytometry
MH  - Hematopoietic Stem Cells/metabolism/pathology
MH  - Humans
MH  - Immunomagnetic Separation
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Male
MH  - Necrosis
MH  - Treatment Outcome
MH  - *Vasculitis/drug therapy/immunology/pathology
EDAT- 2007/10/31 09:00
MHDA- 2007/12/20 09:00
CRDT- 2007/10/31 09:00
PHST- 2007/10/31 09:00 [pubmed]
PHST- 2007/12/20 09:00 [medline]
PHST- 2007/10/31 09:00 [entrez]
AID - 10.1002/art.23070 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2007 Nov;56(11):3847-53. doi: 10.1002/art.23070.