GROWTH OF NEW CORONARY VASCULAR STRUCTURES BY ANGIOGENETIC GROWTH-FACTORS

The efficacy of the human angiogenetic heparin-binding growth factor I (HBGF-I) to initiate site-directed growth of new blood vessels from t he aorta into the myocardium was studied. First, manipulated Escherich ia coli bacteria, which had received the human mRNA-transcript for HBG F I into their genetic material, were cultivated. The growth factor de rived was purified using heparin-Sepharose affinity chromatography. Th e separation and characterization of biologically active alpha- and be ta-chains was carried out using high pressure liquid chromatography (H PLC) of dialyzed and lyophilized samples from the heparin-Sepharose co lumn. One mug HBGF I (alpha-ECGF) was bound to polytetrafluoroethylene (PTFE) sponges, precoated with collagen type I, and implanted between the aorta and the myocardium of the left ventricle in experimental ra ts. Twelve growth factor implants in the experimental group were compa red to six controls receiving uncoated PTFE sponges for 9 weeks. Digit ized computed angiography showed new blood vessels between the aorta a nd the myocardium in 11 of the 12 experimental animals, and retrograde coronary perfusion by these ''new'' vascular structures could be seen . Histology showed no specific structures in the control group (withou t HBGF I). In the experimental group (with HBGF 1) individual vessels with highly differentiated endothelial and smooth muscle cell layers w ere evident. Our experiments proved the feasibility of induced, site-d irected angiogenesis. It is possible to initiate in vivo growth of new ''coronary'' vascular structures between the aorta and the myocardium .