Title
Expression of vascular endothelial growth factor, stromal cell-derived factor-1, and CXCR4 in human limb muscle with acute and chronic ischemia
Author
van Weel, V.
Seghers, L.
de Vries, M.R.
Kuiper, E.J.
Schlingemann, R.O.
Bajema, I.M.
Lindeman, J.H.N.
van Delis-Diemen, P.M.
van Hinsbergh, V.W.M.
van Bockel, J.H.
Quax, P.H.A.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
OBJECTIVE - Vascular endothelial growth factor (VEGF)-induced stromal cell-derived factor-1 (SDF-1) has been implicated in angiogenesis in ischemic tissues by recruitment of CXCR4-positive bone marrow-derived circulating cells with paracrine functions in preclinical models. Here, evidence for this is provided in patients with peripheral artery disease. METHODS AND RESULTS - Expression patterns of VEGF, SDF-1, and CXCR4 were studied in amputated limbs of 16 patients. VEGF-A was expressed in vascular structures and myofibers. SDF-1 was expressed in endothelial and subendothelial cells, whereas CXCR4 was expressed in proximity to capillaries. VEGF-A, SDF-1, and CXCR4 expressions were generally decreased in ischemic muscle as compared with nonischemic muscle in patients with chronic ischemia (0.41-fold, 0.97-fold, and 0.54-fold induction [medians], respectively), whereas substantially increased in 2 patients with acute-on-chronic ischemia (3.5- to 65.8-fold, 3.9- to 19.0-fold, and 4.1- to 30.6-fold induction, respectively). Furthermore, these gene expressions strongly correlated with capillary area. Only acute ischemic tissue displayed a high percentage of hypoxia-inducible factor-1α-positive nuclei. CONCLUSIONS - These data suggest that VEGF and SDF-1 function as pro-angiogenic factors in patients with ischemic disease by perivascular retention of CXCR4-positive cells. Furthermore, these genes are downregulated in chronic ischemia as opposed to upregulated in more acute ischemia. The VEGF-SDF-1-CXCR4 pathway is a promising target to treat chronic ischemic disease. © 2007 American Heart Association, Inc.
Subject
Biology
Biomedical Research
Angiogenesis
Ischemia
Peripheral artery disease
SDF-1
VEGF
chemokine receptor CXCR4
hypoxia inducible factor 1alpha
stromal cell derived factor 1
vasculotropin A
acute disease
adult
aged
angiogenesis
artery disease
article
blood vessel
capillary
chronic disease
controlled study
correlation analysis
down regulation
female
gene control
gene expression
human
human tissue
leg amputation
leg ischemia
leg muscle
limb ischemia
male
muscle cell
muscle ischemia
priority journal
protein expression
protein function
protein induction
upregulation
vascular endothelium
Acute Disease
Aged
Aged, 80 and over
Amputation
Capillaries
Chemokines, CXC
Chronic Disease
Extremities
Female
Humans
Immunohistochemistry
Ischemia
Male
Middle Aged
Muscle, Skeletal
Neovascularization, Physiologic
Peripheral Vascular Diseases
Receptors, CXCR4
Receptors, Vascular Endothelial Growth Factor
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
Vascular Endothelial Growth Factor A
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http://resolver.tudelft.nl/uuid:5c04ced6-bf31-4924-b4ee-4cac021b551e
DOI
https://doi.org/10.1161/atvbaha.107.139642
TNO identifier
239989
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (6), 1426-1432
Document type
article