R. Fasol et al., EXPERIMENTAL USE OF A MODIFIED FIBRIN GLUE TO INDUCE SITE-DIRECTED ANGIOGENESIS FROM THE AORTA TO THE HEART, Journal of thoracic and cardiovascular surgery, 107(6), 1994, pp. 1432-1439
From 10 cultures of manipulated Escherichia coli bacteria expressing t
he class I heparin-binding growth factor polypeptide alpha-endothelial
cell growth factor, 11.2 +/- 0.7 mg alpha-endothelial cell growth fac
tor was eluted by heparin-sepharose affinity chromatography. Analysis
of molecular weight (17,000 kD) was done by sodium dodecyl sulfate-pol
yacrylamide gel electrophoresis and purification of the growth factor
was done by high-performance liquid chromatography. The harvested alph
a-endothelial cell growth factor was proved by protein blotting. To as
sess the growth-promoting activity, we did an endothelial cell growth
assay by comparing adult human endothelial cell control cultures, with
out adding growth factor to the culture medium, with adult human endot
helial eel cultures with 0.02 to 20.0 ng/ml alpha-endothelial cell gro
wth factor and 1.0 ng/ml heparin and with adult human endothelial cell
cultures with alpha-endothelial cell growth factor but without hepari
n. Tritiated thymidine counts proved the significant growth-promoting
activity of alpha-endothelial cell growth factor. In 10 experimental a
nimals modified fibrin glue containing 1 mu g alpha-endothelial cell g
rowth factor was implanted between the aorta and the myocardium of the
left ventricle and results were compared with those in five control a
nimals that received normal fibrin glue without growth factor. After 9
weeks of implantation, angiography and histologic investigation showe
d newly grown vascular structures between the aorta and the myocardium
in all experimental animals, but none in the control animals. Our stu
dy proved the feasibility of initiating site-directed formation of new
blood vessel structures to the heart by a modified fibrin glue implan
t containing angiogenic growth factor alpha-endothelial cell growth fa
ctor.