Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease.
BACKGROUND
We hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF) administration will be safe and will improve endothelial dysfunction and exercise capacity by mobilizing progenitor cells in patients with peripheral arterial disease (PAD).


METHODS
Forty-five patients with PAD received thrice-weekly injections for 2 weeks of 3, 6, or 10 microg/kg per day of GM-CSF or placebo in successive cohorts of 15 subjects randomized 2:1 to drug or placebo. CD34+ mononuclear cell subsets and colony formation assay, endothelial function, ankle-brachial index, and walking capacity were measured.


RESULTS
Granulocyte macrophage colony-stimulating factor administration was safe. After pooling data from GM-CSF cohorts, at 2 weeks, there was a significant increase in total leukocytes (43%, P < .0001), CD34+ cells (46%, P = .035), and colony-forming units (31%, P = .026, week 1). At 12 weeks, endothelial function improved with GM-CSF (flow-mediated vasodilation increased by 59%, P < .01) as did pain-free treadmill walking time (38 seconds, P = .008) and total treadmill walking time (55 seconds, P = .016). Corresponding changes were not observed in the placebo group.


CONCLUSIONS
Granulocyte macrophage colony-stimulating factor therapy in patients with PAD was associated with mobilization of progenitor cells, improvement of endothelial dysfunction, and exercise capacity. The efficacy of strategies designed to mobilize bone marrow progenitors warrants further study in patients with PAD.
Subramaniyam
Veerappan
V
Division of Cardiology, Emory University School of Medicine, 1364 Clifton Rd., Atlanta, GA 30322, USA.
Waller
Edmund K
EK
Murrow
Jonathan R
JR
Manatunga
Amita
A
Lonial
Sagar
S
Kasirajan
Karthikeswar
K
Sutcliffe
Diane
D
Harris
Wayne
W
Taylor
W Robert
WR
Alexander
R Wayne
RW
Quyyumi
Arshed A
AA
D000368:Aged; D055109:Ankle Brachial Index; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D050197:Atherosclerosis / Q000188:drug therapy*; D001853:Bone Marrow / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005080:Exercise Test / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D014664:Vasodilation
D016178:Granulocyte-Macrophage Colony-Stimulating Factor