Am J Cardiovasc Dis 2012;2(1):12-19
Original Article
Higher fasting glucose levels are associated with reduced circulating
angiogenic cell migratory capacity among healthy individuals
Kirstin Aschbacher, Qiumei Chen, Monika Varga, Daniel J. Haddad, Yerem Yeghiazarians, Elissa Epel, Owen M. Wolkowitz,
Matthew L. Springer
Department of Psychiatry, Cardiovascular Research Institute, Division of Cardiology, Eli and Edythe Broad Center of
Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Received September 7, 2011; accepted September 22, 2011; Epub October 3, 2011; Published January 1, 2011
Abstract: Background: Chronic or severe acute elevations in plasma glucose are associated with decreases in the
number and function of circulating angiogenic cells (CACs). However, less is known about whether fasting plasma
glucose levels (FPG) within the normal or pre-diabetic range among healthy individuals are associated with decreased
CAC function. Establishing this relationship is an important step in developing a line of research that may ultimately lead
to preventative lifestyle interventions intended to maximize endogenous CAC function and reduce cardiometabolic disease
risk. Objectives: 1) To examine whether increases in FPG are associated with decreases in CAC migration among
healthy individuals with FPG levels below the threshold for hyperglycemia, and 2) to contrast effect of FPG on CAC
migration toward a pro-angiogenic stimulus (vascular endothelial growth factor; VEGF) with effect on intrinsic cell migratory
capacity (i.e., random migration with no stimulus). Methods: 28 men and women ranging from 20-57 years of age and free
of cardiovascular disease participated in a pilot study, involving a fasting blood draw for FPG and isolation of peripheral
blood mononuclear cells. CAC migration toward VEGF and random cell migration (control) were assessed in vitro. VEGF-
induced migration that was normalized to control migration, representing the VEGF-response component of chemotaxis
independent of motility, was calculated to determine whether any impairment in migration to VEGF was due to lower
specific response to VEGF or to lower non-specific migratory capacity. Results: Increased levels of FPG were associated
in a dose-response fashion with a significantly lower random migration under control conditions (CTRL: r= -.408, p=.031),
no differences in migration to VEGF (r= -.039, p=.842) and a borderline association with VEGF-induced migration
normalized to control migration (VEGF/CTRL: r=.349, p=.069). The relationship between FPG and random migration under
control conditions remained significant when controlling for gender and body mass index (p’s<.05), and became
borderline significant when controlling for age (p=.062). Conclusions: Among healthy individuals, higher fasting glucose
levels, despite falling below the diabetic range, are associated with decreased random CAC migration. These findings
suggest a need for further studies investigating the effects of lifestyle or dietary interventions on glucose regulation and
CAC function. (AJCD1109001).
Keywords:Impaired fasting glucose, metabolism, endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs),
chemotaxis, chemokinesis, motility, migration, angiogenesis, cardiovascular, pre-diabetic
Full Text PDF
Address all correspondence to:
Matthew L. Springer, PhD
Associate Professor of Medicine
University of California, San Francisco
Division of Cardiology, Box 0124
San Francisco, CA 94143-0124
Tel: 415-502-8404
Fax: 415-353-9190
matt.springer@ucsf.edu
Original Article
Higher fasting glucose levels are associated with reduced circulating
angiogenic cell migratory capacity among healthy individuals
Kirstin Aschbacher, Qiumei Chen, Monika Varga, Daniel J. Haddad, Yerem Yeghiazarians, Elissa Epel, Owen M. Wolkowitz,
Matthew L. Springer
Department of Psychiatry, Cardiovascular Research Institute, Division of Cardiology, Eli and Edythe Broad Center of
Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Received September 7, 2011; accepted September 22, 2011; Epub October 3, 2011; Published January 1, 2011
Abstract: Background: Chronic or severe acute elevations in plasma glucose are associated with decreases in the
number and function of circulating angiogenic cells (CACs). However, less is known about whether fasting plasma
glucose levels (FPG) within the normal or pre-diabetic range among healthy individuals are associated with decreased
CAC function. Establishing this relationship is an important step in developing a line of research that may ultimately lead
to preventative lifestyle interventions intended to maximize endogenous CAC function and reduce cardiometabolic disease
risk. Objectives: 1) To examine whether increases in FPG are associated with decreases in CAC migration among
healthy individuals with FPG levels below the threshold for hyperglycemia, and 2) to contrast effect of FPG on CAC
migration toward a pro-angiogenic stimulus (vascular endothelial growth factor; VEGF) with effect on intrinsic cell migratory
capacity (i.e., random migration with no stimulus). Methods: 28 men and women ranging from 20-57 years of age and free
of cardiovascular disease participated in a pilot study, involving a fasting blood draw for FPG and isolation of peripheral
blood mononuclear cells. CAC migration toward VEGF and random cell migration (control) were assessed in vitro. VEGF-
induced migration that was normalized to control migration, representing the VEGF-response component of chemotaxis
independent of motility, was calculated to determine whether any impairment in migration to VEGF was due to lower
specific response to VEGF or to lower non-specific migratory capacity. Results: Increased levels of FPG were associated
in a dose-response fashion with a significantly lower random migration under control conditions (CTRL: r= -.408, p=.031),
no differences in migration to VEGF (r= -.039, p=.842) and a borderline association with VEGF-induced migration
normalized to control migration (VEGF/CTRL: r=.349, p=.069). The relationship between FPG and random migration under
control conditions remained significant when controlling for gender and body mass index (p’s<.05), and became
borderline significant when controlling for age (p=.062). Conclusions: Among healthy individuals, higher fasting glucose
levels, despite falling below the diabetic range, are associated with decreased random CAC migration. These findings
suggest a need for further studies investigating the effects of lifestyle or dietary interventions on glucose regulation and
CAC function. (AJCD1109001).
Keywords:Impaired fasting glucose, metabolism, endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs),
chemotaxis, chemokinesis, motility, migration, angiogenesis, cardiovascular, pre-diabetic
Full Text PDF
Address all correspondence to:
Matthew L. Springer, PhD
Associate Professor of Medicine
University of California, San Francisco
Division of Cardiology, Box 0124
San Francisco, CA 94143-0124
Tel: 415-502-8404
Fax: 415-353-9190
matt.springer@ucsf.edu
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