In animal models the somatostatin analog angiopeptin inhibits intimal hyper
plasia by acting primarily through somatostatin receptor 2 (SSTR-2). Howeve
r, the results of clinical trials using angiopeptin have been disappointing
. In this study we showed that human blood vessels express high levels of S
STR-1 with significantly lower levels of SSTR-2 and -4. Samples of normal v
eins and arteries, as well as atherosclerotic arteries, expressed predomina
ntly SSTR-1. In addition, the levels of SSTR-1 varied between individuals,
indicating that the vascular disease process may have affected SSTR gene ex
pression. Immunocytochemical studies demonstrated that SSTR-1 was present i
n endothelial but not vascular smooth muscle cells. No evidence of SSTR-3 o
r -5 expression was detected in normal or diseased blood vessels. Two endot
helial cell preparations, ECV304 and human umbilical vein endothelial cells
, were investigated and shown to express only SSTR-1 and -4. Exposure of th
ese cells to 10 nM somatostatin or 10 nM SSTR-1-specific agonist resulted i
n alterations to the actin cytoskeleton, as characterized by a loss of acti
n stress fibers coupled with an increase in lamellipodia formation at the p
lasma membrane. These results suggest that the lack of effectiveness of ang
iopeptin in humans may be due to the differential expression of SSTR-1 by h
uman endothelial cells.