Vascular endothelial growth factor (
VEGF) is a mitogenic, angiogenic, and potent mediator of vascular permeability. It plays a role in
injuries, contributes to
edema during the acute stage of tissue damage, and promotes repair during recovery. We recently showed that
VEGF serum levels of
burn patients with a considerable number of damaged vessels were significantly increased. Here, we study the effects of
VEGF on healthy vessels treated with a comparable
VEGF concentration achieved in patients suffering heavy
burns.
VEGF 165 (0.2 mL of 10 ng/mL) or vehicle (
saline 0.9%) was intraluminally applied to umbilical arteries for 90 min at 37 degrees C. Then, the cord was perfused for 4 hr. During perfusion, functional and biochemical parameters were kept within normal physiological ranges. Afterward, the vessels were analyzed applying morphometry, sirius red staining, polarization microscopy, Western blot analysis, and immunohistochemistry. Moreover, cultured human umbilical vein endothelial cells (HUVECs) were treated with
VEGF or vehicle for 90 min and 5.5 hr to examine extracellular matrix (ECM)
proteins and
receptor tyrosine kinases.
VEGF-treated umbilical arteries showed significant tissue
edema and simultaneously an enhancement of
laminin and
collagen types I, III, and IV compared with control arteries. We detected an increase in Flt-1, Flk-1,
osteopontin, and ss(1)-integrin.
VEGF induced
laminin early in HUVECs as measured by flow cytometry. In parallel,
VEGF induced a higher amount of
osteopontin, ss(1)-integrin, and both
receptor tyrosine kinases in endothelial cells within 90 min. Intraluminal application of
VEGF enhances ECM
protein,
osteopontin, and ss(1)-integrin production of the endothelium, while it still generates tissue
edema.
VEGF initiates
vascular remodeling as early as it generates
edema, even if the target vessel is not damaged.
Osteopontin and ss(1)-integrin, both induced by
VEGF, may play an important role in the
vascular remodeling process.