PDGF-BB induced chemotaxis is impaired in aged capillary endothelial cells.
The object of this study was to determine if the decreased angiogenesis in the healing wounds of the aged is due to the failure of endothelial cells to respond to locally produced growth factors. Endothelial cells isolated from wound sponges implanted in aged (24-month-old) and young (2-month-old) rats were tested for their chemotactic response to the BB isoform of platelet-derived growth factor (PDGF-BB). A similar number of cells isolated from both old and young rats stained positive (75-90%) for acetylated-LDL uptake, and the same number of viable cells was used in the chemotaxis assay. Endothelial cells from both old and young rats migrated in a dose-dependent (0.1-3.0 ng/ml) manner in response to PDGF-BB. At all concentrations tested, PDGF-BB elicited the migration of more endothelial cells from the young rats. The difference between the number of young and old cells that responded to PDGF-BB was statistically significant at the 1.0 ng/ml and 3.0 ng/ml concentrations. These results suggest that the impaired angiogenic response in the healing of wounds of the aged is due to altered endothelial cell reaction to the growth factors in the wound microenvironment.
Phillips
G D
GD
Department of Surgery, University of Minnesota, Minneapolis 55455.
Stone
A M
AM
D000375:Aging / Q000473:pathology*; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin