Disease relevance of Angiopeptin

• The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit [1].
• The late losses were 0.31 +/- 0.59 and 0.30 +/- 0.62 mm (P = .81) and the restenosis rates (> 50% diameter stenosis at follow-up) were 36% and 37% (P = .85) in the angiopeptin- and placebo-treated groups, respectively [2].
• In view of its potent inhibitory effect on smooth muscle cell replication, angiopeptin may have clinical utility in preventing restenosis after percutaneous transluminal coronary angioplasty and in preventing accelerated coronary atherosclerosis after cardiac transplantation [3].
• We conclude that angiopeptin, at the high intravenous dose used, does not significantly reduce the development of chronic hypoxic pulmonary hypertension in rats [4].
• Angiopeptin was infused intravenously (90-100 microg/kg/day) by minipumps in 10 rats during a 3-week exposure to hypobaric hypoxia and in six normoxic rats [4].

High impact information on Angiopeptin

• Continuous subcutaneous angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model [5].
• This study evaluated the efficacy and the optimal mode of administration of angiopeptin, a somatostatin analogue with antiproliferative activity, in a porcine coronary in-stent restenosis model [5].
• The aim of this study was to analyze the effect of angiopeptin pretreatment on the level of expression of the c-fos and c-jun protooncogenes, early markers of smooth muscle cell proliferation, after balloon denudation of rabbit aorta [6].
• CONCLUSIONS: Our results show that the inhibitory effect of angiopeptin on neointimal thickening is related to events that occur very early after injury and suggest that the inhibition of smooth muscle cell activation may be responsible, at least in part, for this effect [6].
• In addition, we provide data to suggest that the long-acting somatostatin analogues octreotide and angiopeptin inhibit IGF-I- and basic fibroblast growth factor (b-FGF)- induced human coronary artery SMC proliferation [7].

Chemical compound and disease context of Angiopeptin

• Vasoconstrictor responses of isolated lungs to acute hypoxia were not affected by angiopeptin [4].
• 2. The effect of angiopeptin on myointimal hyperplasia was studied in a rabbit model of arterial balloon catheter injury where the rabbits were made hypercholesterolaemic by a 0.5% cholesterol diet [8].

Biological context of Angiopeptin

• Angiopeptin inhibits oncogene induction in rabbit aorta after balloon denudation [6].
• Angiopeptin inhibits 3H-thymidine incorporation into rat carotid artery explants, suggesting a local effect on autocrine or paracrine mechanisms regulating cell growth [3].
• Disposition and tissue distribution of angiopeptin in the rat [9].
• The kinetics of angiopeptin following sc administration closely resembled those following iv administration due to rapid absorption [9].
• The pharmacokinetics of angiopeptin can be described by a two-compartment model [9].

Anatomical context of Angiopeptin

• Angiopeptin inhibits the development of intimal hyperplasia in swine coronary arteries after balloon injury [10].
• Angiopeptin can be delivered intramurally via the Wolinsky porous balloon and reduces myointimal hyperplasia only in the area distal to the local drug delivery site (downstream effect), possibly by healing the injured endothelium, by transport via the vasa vasora, and/or by systemic effect [1].
• However, in the lower abdominal aorta, where balloon injury without local delivery was performed, there was a significant reduction of myointimal hyperplasia in the highest-concentration angiopeptin group (P < .001 versus the control group) [1].
• Angiopeptin, a cyclic octapeptide analogue of somatostatin, markedly inhibits myointimal proliferation in response to endothelial cell injury in the rat carotid artery, rabbit aorta and iliac arteries and in coronary arteries of transplanted rabbit hearts [3].
• These results suggest that the lack of effectiveness of angiopeptin in humans may be due to the differential expression of SSTR-1 by human endothelial cells [11].

Associations of Angiopeptin with other chemical compounds

• In contrast, angiopeptin, triptorelin and TRH exhibited a K(1) of 4.0 x 10(6), 5.3 x 10(6) and 20.2 x 10(6)M(-1), respectively, and a K(2) of 0.4 x 10(6), 0.5 x 10(6) and 1.4 x 10(6)M(-1), respectively [12].
• The x-reciprocal and the double-reciprocal plots indicated the presence of two portions of straight lines for angiopeptin, triptorelin and the thyrotropin releasing hormone (TRH), and therefore the probable existence of a second-order interaction which causes the deviation from the 1:1 model [12].
• 4. Inhibition of MEK1 or Src, but not PKA, PI 3-kinases or tyrosine kinases, by reportedly selective inhibitors reduced sst(2)-mediated responses by somatostatin, but not angiopeptin [13].
• Inhibition of vascular cell proliferation by angiopeptin was evaluated by tritiated thymidine incorporation into the balloon-injured rabbit aorta [14].
• Solution conformation by NMR and molecular modeling of three sulfide-free somatostatin octapeptide analogs compared to angiopeptin [15].

Gene context of Angiopeptin

• In animal models the somatostatin analog angiopeptin inhibits intimal hyperplasia by acting primarily through somatostatin receptor 2 (SSTR-2) [11].
• We have investigated the actions of somatostatin (SRIF) and angiopeptin on cell proliferation of CHO-K1 cells expressing the recently cloned rat sst2(b) receptor (CHOsst2(b)) and compared these to their effects in cells expressing the sst2(a) receptor (CHOsst2(a)) [16].
• 1. Somatostatin (SRIF) exerts antiproliferative effects, and angiopeptin (an sst2/sst5 receptor-selective analogue) has recently been evaluated in clinical trials for the prophylaxis of restenosis following coronary angioplasty [17].
• 6. SRIF (0.1-1000 nM) caused a concentration-dependent (pIC50=8.04+/-0.08) inhibition of bFGF-stimulated re-growth in VSMC, whereas angiopeptin displayed weak agonist activity, only inhibiting bFGF-stimulated re-growth at concentrations greater than 100 nM [17].
• Rather, SRIF (0.1-1000 nM) and angiopeptin (0.1-1000 nM) stimulated basal re-growth and proliferation of CHOsst2(b) cells in a concentration-dependent manner (estimated pEC50 values of 7.8 and 7.9, respectively) [16].

Analytical, diagnostic and therapeutic context of Angiopeptin

• CONCLUSIONS: This study shows that continuous subcutaneous treatment with angiopeptin after stent implantation significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia [5].
• A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA [2].
• Long-term effects of angiopeptin treatment in coronary angioplasty: reduction of clinical events but not angiographic restenosis [18].
• When angiopeptin was started 1 hour after denudation (group 3), however, the neointimal area (0.52 +/- 0.09 mm2) and the neointima/media ratio (0.76 +/- 0.10) were not statistically different from the control group [6].
• Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously [1].

References