Extensive smooth muscle cell proliferation is the major event leading to the narrowing or occlusion of the lumen of the coronary arteries of patients undergoing
heart transplantation or percutaneous transluminal coronary angioplasty. The smooth muscle cell proliferation in transplant
atherosclerosis may be initiated by immunologic events, allowing the vascular smooth muscle cells to respond with migration and proliferation to circulating
growth factors as well as
chemoattractants and
growth factors released by inflammatory cells and smooth muscle cells themselves. The
somatostatin analog
angiopeptin is a cyclic octapeptide that has different binding affinities for different
somatostatin receptors compared with the parent compound itself. The antiproliferative effects of
angiopeptin have been demonstrated in vitro in several tumor cell lines. In a rabbit model of heterotopic heart transplant-accelerated
coronary atherosclerosis,
angiopeptin has been shown to attenuate myointimal
hyperplasia. Further studies in simpler models of myointimal
hyperplasia have shown that
angiopeptin will inhibit smooth muscle cell proliferation after
vascular injury. Further,
angiopeptin inhibits
thymidine uptake in vitro in pig coronary arteries.
Angiopeptin also exerts its inhibitory effect at a very early stage after injury: an 8-hour delay of treatment abolishes the inhibitory effect of
angiopeptin on smooth muscle cell proliferation (intimal
hyperplasia). On the basis of the experimental data, clinical studies of the inhibitory effect of
angiopeptin on prevention of transplant
atherosclerosis in heart transplant patients and prevention of restenosis after coronary artery angioplasty are ongoing, as well as are studies in patients undergoing saphenous vein
coronary artery bypass surgery.