Circulating progenitor cells and coronary microvascular dysfunction: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD).
Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs.



In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine. Peripheral blood CPCs were measured using flow cytometry for expression of CD34, CD133, CXCR4, and VEGFR2.



Subjects were 53 ± 11 years, BMI 30 ± 8; 44% hypertensive, 11% diabetic, 23% hyperlipidemic and 7% smokers. Lower CFR correlated inversely with higher levels of hematopoietic-enriched CD34+ (r = -0.23, p = 0.011), CD34+/CD133+ (r = -0.24, p = 0.008), and CD34+/CXCR4+ (r = -0.19, p = 0.036) cells. In multivariable regression analyses, after adjusting for traditional cardiovascular risk factors, lower CFR remained significantly associated with elevated levels of CD34+ (β -0.18, p = 0.042), CD34+/CD133+ (β -0.24, p = 0.036), and CD34+/CXCR4+ (β -0.22, p = 0.050) cells. We found no association between CFR and CD34+/VEGFR2+ cells.



In women with non-obstructive CAD, impaired CFR is associated with higher levels of CPCs, suggesting that chronic myocardial ischemia from CMD stimulates CPC mobilization. The functional significance of elevated CPCs in these subjects requires further investigation as a potential biomarker and treatment target.
Emory University School of Medicine, Atlanta, GA, USA.
Girum
G
Mekonnen
Emory University School of Medicine, Atlanta, GA, USA.
Salim S
SS
Hayek
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Puja K
PK
Mehta
Emory University School of Medicine, Atlanta, GA, USA.
Qunna
Q
Li
Emory University School of Medicine, Atlanta, GA, USA.
Ernestine
E
Mahar
Emory University School of Medicine, Atlanta, GA, USA.
Liping
L
Mou
University of Pittsburgh, Pittsburgh, PA, USA.
Tanya S
TS
Kenkre
University of Florida, Gainesville, FL, USA.
John W
JW
Petersen
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Babak
B
Azarbal
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Bruce
B
Samuels
University of Florida, Gainesville, FL, USA.
R David
RD
Anderson
University of British Columbia, Canada.
Tara
T
Sedlak
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Melody
M
Zaya
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Megha
M
Agarwal
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Afsaneh
A
Haftbaradaran
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
Margo
M
Minissian
University of Florida, Gainesville, FL, USA.
Eileen
E
Handberg
University of Florida, Gainesville, FL, USA.
Carl J
CJ
Pepine
University of Florida, Gainesville, FL, USA.
Christopher R
CR
Cogle
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, USA.
C Noel
CN
Bairey Merz
Emory University School of Medicine, Atlanta, GA, USA.
Edmund K
EK
Waller
Emory University School of Medicine, Atlanta, GA, USA. Electronic address: aquyyum@emory.edu.
Arshed A
AA
Quyyumi
D000368:Aged; D000792:Angiography; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood*; D003326:Coronary Circulation; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007511:Ischemia / Q000097:blood*; D008833:Microcirculation; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood; D054555:National Heart, Lung, and Blood Institute (U.S.); D012307:Risk Factors; D013234:Stem Cells / Q000166:cytology*; D014481:United States; D014652:Vascular Diseases / Q000097:blood; D016387:Women's Health
D015415:Biomarkers
Circulating progenitor cells; Coronary flow reserve; Microvascular function