Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model.
OBJECTIVE
Histopathologic studies indicate that aneurysms treated with Guglielmi detachable coils (GDCs) have avascular centers with fibrosis mostly at the aneurysm periphery. We hypothesized that vascular endothelial growth factor (VEGF) released from a coil promotes clot organization, hyperplasia, and endothelial proliferation to facilitate closure of the aneurysm neck.


METHODS
GDC segments were inserted into ligated common carotid arteries (CCAs) of adult male rats for 14 days. Coil segments (4-mm) were unmodified, modified with type I collagen (2.4 mg/mL), or modified with type I collagen and recombinant human VEGF-165 (rhVEGF; 500 microg/mL). CCA segments were harvested and coils removed for scanning electron microscopy (SEM).


RESULTS
Collagen/rhVEGF coils (n = 11) resulted in marked reductions in CCA lumen area (0.03 mm(2)) compared with coils (n = 9, 0.21 mm(2), P <.001) and collagen coils (n = 5, 0.13 mm(2), P <.001). Collagen/rhVEGF coils (n = 11) also resulted in marked reductions in CCA diameter (0.19 mm) compared with coils (n = 9, 0.50 mm, P <.001) and collagen coils (n = 5, 0.40 mm, P <.001). Wall thickness was greater for the collagen/rhVEGF coil segments (0.22 mm) compared with coils (0.09 mm, P <.001), and the collagen coils (0.15 mm, P =.06). CCA segments containing collagen/rhVEGF coils also displayed Factor VIII positivity and were completely encapsulated in fibrotic tissue, while the unmodified and collagen coils were essentially smooth, as seen by SEM.


CONCLUSIONS
These results suggest that rhVEGF may be beneficial in promoting endothelialization, clot organization, and tissue integration of the coils. This is the first study to hypothesize that rhVEGF may be useful as a surface modification to GDCs for enhancing their therapeutic effects in the treatment of cerebral aneurysms.
Abrahams
J M
JM
Department of Neurosurgery, Institute for Medicine and Engineering, The Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Forman
M S
MS
Grady
M S
MS
Diamond
S L
SL
D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D020099:Coated Materials, Biocompatible; D003094:Collagen; D004621:Embolization, Therapeutic / Q000295:instrumentation*; D016228:Endothelial Growth Factors / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004867:Equipment Design; D005169:Factor VIII / Q000378:metabolism; D002532:Intracranial Aneurysm / Q000473:pathology / Q000628:therapy*; D008222:Lymphokines / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010984:Platinum; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013927:Thrombosis / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020099:Coated Materials, Biocompatible; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010984:Platinum; D005169:Factor VIII; D003094:Collagen