Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease

Veerappan Subramaniyam, Edmund K. Waller, Jonathan R Murrow, Amita Manatunga, Sagar Lonial, Karthikeswar Kasirajan, Diane Sutcliffe, Wayne Harris, W. Robert Taylor, R. Wayne Alexander, Arshed A. Quyyumi

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Abstract

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 μg/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.

Original languageEnglish (US)
JournalAmerican Heart Journal
Volume158
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

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Peripheral Arterial Disease
Granulocyte-Macrophage Colony-Stimulating Factor
Bone Marrow
Exercise
Walking
Placebos
Stem Cells
Ankle Brachial Index
Vasodilation
Meta-Analysis
Leukocytes
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. / Subramaniyam, Veerappan; Waller, Edmund K.; Murrow, Jonathan R; Manatunga, Amita; Lonial, Sagar; Kasirajan, Karthikeswar; Sutcliffe, Diane; Harris, Wayne; Taylor, W. Robert; Alexander, R. Wayne; Quyyumi, Arshed A.

In: American Heart Journal, Vol. 158, No. 1, 01.01.2009.

Research output: Contribution to journalArticle

Subramaniyam, Veerappan ; Waller, Edmund K. ; Murrow, Jonathan R ; Manatunga, Amita ; Lonial, Sagar ; Kasirajan, Karthikeswar ; Sutcliffe, Diane ; Harris, Wayne ; Taylor, W. Robert ; Alexander, R. Wayne ; Quyyumi, Arshed A. / Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. In: American Heart Journal. 2009 ; Vol. 158, No. 1.
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abstract = "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 μg/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.",
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AU - Manatunga, Amita

AU - Lonial, Sagar

AU - Kasirajan, Karthikeswar

AU - Sutcliffe, Diane

AU - Harris, Wayne

AU - Taylor, W. Robert

AU - Alexander, R. Wayne

AU - Quyyumi, Arshed A.

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