Abstract
BackgroundIn 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.MethodsWe 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.ResultsCompared 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) (R2 = 0.45; P<0.05).ConclusionsThe 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.
Highlights
Ischemic heart disease (IHD) remains the leading cause of death and a major cause of disability among women
We have previously shown that bone-marrow derived angiogenic cells (BMDAC) isolated from diabetic patients have cytoskeletal alterations preventing responsiveness to growth factor stimulation, which can be corrected by use of exogenous nitric oxide (NO) [24]
Study protocol and study population The Women’s Ischemia Syndrome Evaluation (WISE) is an NHLBI-sponsored study aimed at improving diagnostic evaluation and understanding pathological mechanisms of IHD in women
Summary
Ischemic heart disease (IHD) remains the leading cause of death and a major cause of disability among women. The Women’s Ischemia Syndrome Evaluation (WISE) was initiated by the National Heart, Lung and Blood Institute (NHLBI) to improve our understanding of pathological mechanisms and diagnostic evaluation of IHD in women [4]. Among such women with ischemia but no obstruction on coronary angiograms, microvascular coronary dysfunction (MCD), as evidenced by decreased coronary flow reserve (CFR) to intracoronary adenosine, was the best independent predictor of major cardiovascular events over 5.4 years of follow- up [5]. 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
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