Expression of vascular endothelial growth factor, stromal cell-derived factor-1, and CXCR4 in human limb muscle with acute and chronic ischemia
van Weel, V.
de Vries, M.R.
van Delis-Diemen, P.M.
van Hinsbergh, V.W.M.
van Bockel, J.H.
TNO Kwaliteit van Leven
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.
To reference this document use:
Peripheral artery disease
chemokine receptor CXCR4
hypoxia inducible factor 1alpha
stromal cell derived factor 1
Aged, 80 and over
Peripheral Vascular Diseases
Receptors, Vascular Endothelial Growth Factor
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A
Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (6), 1426-1432