title: Number and function of bone-marrow derived angiogenic cells and coronary flow reserve in women without obstructive coronary artery disease: a substudy of the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE).
abstract: BACKGROUND
  In women with ischemia and no obstructive coronary artery disease, the Women's Ischemic Syndrome Evaluation (WISE) observed that microvascular coronary dysfunction (MCD) is the best independent predictor of adverse cardiovascular events. Since coronary microvascular tone is regulated in part by endothelium, we hypothesized that circulating endothelial cells (CEC), which reflect endothelial injury, and the number and function of bone-marrow derived angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve as biomarkers for decreased coronary flow reserve (CFR) and MCD.
  
  
  METHODS
  We studied 32 women from the WISE cohort. CFR measurements in response to intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC colonies and CEC in peripheral blood samples. BMDAC function was assessed by assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable nitric oxide (NO). These findings were compared with a healthy reference group and also entered into a multivariable model with CFR as the dependent variable.
  
  
  RESULTS
  Compared with a healthy reference group, women with MCD had lower numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936 (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis showed strong correlation of CFR to the combination of BMDAC colony count and CD34+ cell function (migration and NO) (R(2) = 0.45; P<0.05).
  
  
  CONCLUSIONS
  The BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women with MCD and are independently associated with CFR. These circulating cells may provide mechanistic insights into MCD in women with ischemia.
authors: Division of Nephrology, Hypertension & Transplantation, University of Florida, Gainesville, Florida, United States of America.
authors: Rajesh
authors: R
authors: Mohandas
authors: Larysa
authors: L
authors: Sautina
authors: Shiyu
authors: S
authors: Li
authors: Xuerong
authors: X
authors: Wen
authors: Tianyao
authors: T
authors: Huo
authors: Eileen
authors: E
authors: Handberg
authors: Yueh-Yun
authors: YY
authors: Chi
authors: C Noel Bairey
authors: CN
authors: Merz
authors: Carl J
authors: CJ
authors: Pepine
authors: Mark S
authors: MS
authors: Segal
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002452:Cell Count; D017023:Coronary Angiography; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D054555:National Heart, Lung, and Blood Institute (U.S.); D018919:Neovascularization, Physiologic; D014481:United States