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Marie L. Foegh - One of the best experts on this subject based on the ideXlab platform.

  • short term Angiopeptin therapy and the incidence of graft vessel disease after heart transplantation
    Journal of Heart and Lung Transplantation, 2002
    Co-Authors: B Meiser, Marie L. Foegh, M Mueller, Wolfgang Von Scheidt, Bruno Reichart
    Abstract:

    Abstract Background Graft vessel disease, the major limitation for long-term success after heart transplantation, is triggered by injury to the graft vessel endothelium, resulting in the expression of adhesion molecules, the migration of leukocytes into the graft, and the release of growth factors. Angiopeptin, a stable analog of somatostatin, is a growth-hormone inhibitor with additional anti-proliferative effects. We evaluated Angiopeptin for prevention of graft vasculopathy after cardiac transplantation in the first prospective, randomized, double-blind, clinical trial. Methods Thirty-one patients received treatment with either Angiopeptin ( n = 13) or placebo ( n = 18). Patients were randomized according to the presence of hypercholesterolemia, recipient cytomegalovirus-antibody status, and donor age. All patients received standard triple-drug immunosuppression. Angiopeptin 1.5 mg or placebo was given subcutaneously immediately before surgery and twice a day after transplantation from Day 1 to Day 14. Furthermore, 1.5 mg was added to each liter of cardioplegic solution, 1.5 mg was given intravenously during surgery, and another 3 mg was given during the first 6 post-operative hours. During the first post-operative year, Angiopeptin 1.5 mg or placebo was added to each treatment for acute rejection (twice a day subcutaneously). Baseline angiography was performed within the first 4 post-operative weeks and annually thereafter. Twenty-three patients each underwent an additional intracoronary ultrasound. Results One- and 4-year survival rates were comparable: 85% and 85% for the group receiving Angiopeptin, and 89% and 78% for the placebo group, respectively. One patient in the control group died of myocardial infarction caused by graft vessel disease. Although the mean number of rejection and infection episodes was similar, the overall incidence of newly occurring graft vessel disease after 2 and 4 years was greater in the control cohort: 9% vs 38% after 2 years and 27% vs 44% after 4 years ( p = 0.183, 0.448). Comparison of the results of intracoronary ultrasound performed in a sub-group of patients confirmed that trend: the modified Stanford score, the mean intimal thickness, and the mean intimal index were lower in the Angiopeptin group. Again, because of the relatively small number of patients available for evaluation, the difference did not reach statistical significance. Conclusions Short-term peri-operative Angiopeptin treatment along with additional injections during rejection episodes within the first year resulted in a marked decrease in graft vessel disease 2 and 4 years after heart transplantation. Based on our results, continuous, long-term application of slow-release Angiopeptin could significantly decrease or even prevent graft vessel disease.

  • single dose intramuscular administration of sustained release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Coronary Artery Disease, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Ran Kornowski, Orville Bramwell, Seedabarum S Cathapermal, Martin B Leon
    Abstract:

    BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. METHODS: Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). RESULTS: A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. CONCLUSIONS: This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

  • continuous subcutaneous Angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Circulation, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Seedabarum S Cathapermal, Roxana Mehran, Gary S Mintz, Chiu S Wong, Martin B Leon
    Abstract:

    Background In-stent restenosis results primarily from neointimal hyperplasia. 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. Methods and Results Forty pigs were randomly assigned to one of four groups (n=10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 μg Angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 μg/kg total dose), and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent dia...

  • Angiopeptin, a Somatostatin Analogue, Inhibits Rat Coronary Artery and Aorta Smooth Muscle Cell Proliferation Induced by the Thromboxane A2 Mimetic U46619
    Prostaglandins, 1997
    Co-Authors: Yejun Zhao, Marie L. Foegh
    Abstract:

    Thromboxane A2 (TXA2) is a potent mitogenic agent. Its synthesis is increased in transplant patients during rejection episodes, which is the suspected etiology of accelerated transplant arteriosclerosis. Angiopeptin, a stable analogue of somatostatin, inhibits arterial myointimal thickening in a number of vascular balloon injury models of angioplasty and in vivo models of transplant arteriosclerosis. In this study, we investigated whether TXA2-induced smooth muscle cell proliferation is inhibited by Angiopeptin in vitro. Primary rat coronary and aorta smooth muscle cells were cultured in the presence of U46619, a TXA2 mimetic. Proliferation induced by U46619, as determined by 3H-thymidine incorporation, was abrogated by two specific thromboxane receptor antagonists, SQ 30741 and SQ 29548, indicating that the effect of U46619 on smooth muscle cells is a specific receptor-mediated response. We found Angiopeptin to inhibit proliferation following exposure of both coronary and aorta smooth muscle cells to varying concentrations of U46619 for 3 and 6 days. This study demonstrates that U46619 exerts a specific receptor-mediated response stimulating the rat coronary and aorta smooth muscle cell proliferation. This mitogenic effect is obtained by increasing the G1 to S transition rate. Angiopeptin inhibits thromboxane-induced cell proliferation to the same extent as a thromboxane antagonist. This inhibition is obtained by maintaining the noncycling fraction in that Angiopeptin prevents a progression from G0-G1 to S phase.

  • local Angiopeptin delivery using coated stents reduces neointimal proliferation in overstretched porcine coronary arteries
    Journal of Invasive Cardiology, 1996
    Co-Authors: De Scheerder, Marie L. Foegh, S Cathapermal, Krzysztof Wilczek, Van Dorpe J, Eric Verbeken, Kai Wang, Walter Desmet, Etienne Schacht, De Geest H
    Abstract:

    BACKGROUND: Systemic administration of Angiopeptin has been shown to inhibit myointimal thickening after arterial injury in several animal species. METHODS AND RESULTS: To explore to what extent high and long-lasting local concentrations of Angiopeptin influence the healing process after vascular injury, tantalum balloon-expandable stents were first coated with a polymer loaded with Angiopeptin 250 µg. Implantation of these stents in porcine coronary arteries resulted in tissue concentrations of 10.7 pg/ml wet weight in the stented arterial segment 24 hours after stent implantation, gradually declining to 2.0 pg/ml wet weight at day 8. Finally, 20 pigs were randomly treated with either an Angiopeptin-loaded or a blank-coated stent. At baseline, the angiographic parameters were similar between both groups but, after 6 weeks, the minimal luminal diameter of the stented arterial segment was larger in the Angiopeptin-treated pigs when compared to controls (2.20 +/- 0.57 mm vs 1.57 +/- 0.68 mm, p < 0.01) This angiographic finding was confirmed by post-mortem morphometry where the respective lumen area values were 1.00 +/- 0.54 mm2 and 0.43 +/- 0.28 mm2 (p < 0.01). CONCLUSION: Polymer coated stents can be loaded with Angiopeptin, which after implantation in porcine right coronary arteries result in high local tissue concentrations gradually declining over more than 8 days. These high local concentrations inhibit myointimal proliferation induced by poly(organo)phosphazene coated overstretched stents.

Ml Foegh - One of the best experts on this subject based on the ideXlab platform.

  • the somatostatin analog Angiopeptin does not reduce chronic hypoxic pulmonary hypertension in rats
    Experimental Biology and Medicine, 1996
    Co-Authors: E J Sidney, Ml Foegh, S S Cathapermal, Vaclav Hampl, Daniel P Nelson, Stephen L Archer, E K Weir
    Abstract:

    AbstractAngiopeptin is an analog of somatostatin-14, which has been found to inhibit cellular proliferation in several models of systemic vascular injury. As proliferation plays a major role in pulmonary hypertension, we examined the hypothesis that Angiopeptin would inhibit the development of chronic hypoxic pulmonary hypertension in the rat. Angiopeptin was infused intravenously (90-100 μg/kg/day) by minipumps in 10 rats during a 3-week exposure to hypobaric hypoxia and in six normoxic rats. Normal saline was infused in six hypoxic control rats and in seven normoxic control rats. Angiopeptin produced no significant difference in mean pulmonary arterial pressure and resistance, right ventricular weight, or medial thickness of small pulmonary vessels. Vasoconstrictor responses of isolated lungs to acute hypoxia were not affected by Angiopeptin. We conclude that Angiopeptin, at the high intravenous dose used, does not significantly reduce the development of chronic hypoxic pulmonary hypertension in rats.

  • Angiopeptin experimental and clinical studies of inhibition of myointimal proliferation
    Kidney International, 1995
    Co-Authors: Ml Foegh, P W Ramwell
    Abstract:

    Angiopeptin is a long-acting cyclic octapeptide with pharmacologic actions clearly resembling those of the natural hormone somatostatin, but with different binding affinities for the five known somatostatin receptors. It is a potent inhibitor of myointimal migration and proliferation in animal models of angioplasty and organ transplantation. Experimentally, Angiopeptin inhibits transplant arteriosclerosis in cardiac, renal and vascular allografts. The mechanisms are thought to involve abrogation of the increase of insulin-like growth factor (IGF-I) and other growth factors that occur in the vascular wall following immune or mechanical injury. Angiopeptin also restores the endothelium-dependent vasodilatory response to acetylcholine. Clinically, Angiopeptin is safe in cardiac transplant patients and shows promise in inhibiting coronary transplant arteriosclerosis. Furthermore, in large clinical trials, Angiopeptin (given as a continuous infusion for 5 days) inhibits serious clinical events, such as myocardial infarction, death and revascularization at 6 and 12 months following percutaneous transluminal coronary angioplasty. It has few serious side effects.

  • Angiopeptin a somatostatin 14 analogue decreases adhesiveness of rat leukocytes to unstimulated and il 1β activated rat heart endothelial cells
    Life Sciences, 1995
    Co-Authors: Dariusz Leszczynski, Yejun Zhao, Michael D Josephs, Kevin Dunsky, Ml Foegh
    Abstract:

    We have previously demonstrated that somatostatin-14 and its octapeptide analogue, Angiopeptin, decrease the ability of rat heart endothelial cells to bind leukocytes [Leszczynski, et al., Reg. Pept. 43 (1993) 131–140]. Here, we examined whether exposure of leukocytes to Angiopeptin modifies their adhesiveness to the unstimulated and to IL-1β-activated endothelium. Monolayers of unstimulated endothelial cells bind 274 ± 12 leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to Angiopeptin (1 μM) reduced significantly (p < 0.05) adhesion of leukocytes from 274 ± 12 to 188 ± 10, 185 ± 8 and 172 ± 3 cells/mm2, respectively. Stimulation of endothelial cells with IL-1β (100U/ml) for 24 hours increased endothelial adhesiveness from 274 +- 12 to 381 ± 17 adhering leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to Angiopeptin (1μM) reduced significantly (p < 0.05) binding of leukocytes to IL-1β-activated endothelium from 381 ± 17 to 237 ± 8, 254 ± 11 and 248 ± 13 cells/mm2, respectively. Angiopeptin had no effect on the expression of lymphocyte function-associated molecule-1 (LFA-1; CDlla/CD18) by leukocytes, as assessed by flow cytometry. This suggests that Angiopeptin modulates adhesive properties of leukocytes by (1) altering the expression of other than LFA-1 adhesion molecule(s) and/or (2) modulating the affinity of adhesion molecule(s) expressed by leukocytes. In conclusion, our results demonstrate that Angiopeptin reduces leukocyte adhesiveness to unstimulated and to IL-1β-activated endothelium. It suggests that Angiopeptin may suppress immune response via modulation of the leukocyte-endothelial interaction.

  • the effect of porous infusion balloon delivered Angiopeptin on myointimal hyperplasia after balloon injury in the rabbit
    Circulation, 1993
    Co-Authors: Mun K Hong, Ml Foegh, P W Ramwell, Tahira Bhatti, B J Matthews, K S Stark, S S Cathapermal, Kenneth M Kent
    Abstract:

    BACKGROUND Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of Angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied. METHODS AND RESULTS Three rabbits received 125I-Angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three Angiopeptin groups receiving 1, 10, or 100 micrograms/mL of Angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the Angiopeptin groups compared with the control group. 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). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the Angiopeptin-treated animals, endothelial cells were present at both locations. CONCLUSIONS 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.

  • Angiopeptin a treatment for accelerated myointimal hyperplasia
    Journal of Heart and Lung Transplantation, 1992
    Co-Authors: Ml Foegh
    Abstract:

    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.

Peter W Ramwell - One of the best experts on this subject based on the ideXlab platform.

  • Angiopeptin inhibits thymidine incorporation by explants of porcine coronary arteries
    Journal of Cardiovascular Pharmacology, 1997
    Co-Authors: Roberto Vargas, Barbara Wroblewska, A Rego, Sam Cathapermal, Peter W Ramwell
    Abstract:

    Angiopeptin, a stable octapeptide analog of somatostatin, inhibits proliferation in a variety of cancer cell lines. We studied the effect of Angiopeptin on 3H-thymidine uptake into ring segments from the porcine coronary tree. The incorporation of 3H-thymidine into segments of porcine left anterior descending (LAD) coronary artery was time dependent and reached a plateau after 48 h. The addition of Angiopeptin (48.1 and 96.2 nM) to the culture medium significantly inhibited 3H-thymidine incorporation into the segments by 36.7 +/- 10.1% and 48.3 +/- 2.3% of the control, respectively. Forskolin (100 microM), inhibited 3H-thymidine incorporation (52.7 +/- 10.1%) to the same degree as did Angiopeptin (96.2 nM). Incubation of the segments with 125I-labeled Angiopeptin, for 2 h at 37 degrees C, showed Angiopeptin uptake to be time dependent and exhibited a first-order kinetics, reaching equilibrium after 30 min. Autoradiographic studies showed a uniform distribution of Angiopeptin within the endothelium, media, and adventitia. Most of the labeling was associated with the nuclei of the cells. Angiopeptin, after 30-min incubation, did not significantly modify the basal levels of cyclic adenosine monophosphate (cAMP). In contrast, forskolin (100 microM) elicited a 50-fold increase of the basal levels of cAMP. These results indicate that in addition to its endocrine effects, Angiopeptin reduces the rate of proliferation by acting directly on the vessel wall.

  • early inhibition of myointimal proliferation by Angiopeptin after balloon catheter injury in the rabbit
    Journal of Vascular Surgery, 1994
    Co-Authors: Marie L. Foegh, Satish Asotra, John V Conte, Marcus Howell, Elliott Kagan, Kiran Verma, Peter W Ramwell
    Abstract:

    Abstract Purpose: Coronary artery restenosis after percutaneous transluminal angioplasty occurs in more than 40% of patients. Angiopeptin, a stable synthetic octapeptide analogue of somatostatin, attenuates accelerated coronary artery myointimal thickening in rabbit cardiac allografts and myointimal thickening after arterial injury. In this study the temporal relationship between the Angiopeptin treatment schedule and efficacy was explored. The relationship between inhibition of myointimal thickening by Angiopeptin and inhibition of vascular cell proliferation was also examined. Methods: The aorta and the common and external iliac arteries of the rabbit underwent balloon injury. Angiopeptin (2 to 200 μg/kg/day) was administered for 1 day before injury and for 1, 5, and 21 days after injury. Morphometric studies were performed to determine measurement of intimal thickening. Inhibition of vascular cell proliferation by Angiopeptin was evaluated by tritiated thymidine incorporation into the balloon-injured rabbit aorta. Thymidine was either administered intraperitoneally or added ex vivo to aorta segments of rabbits treated with Angiopeptin (2, 20, or 200 μg/kg/day) from 1 day before injury until sacrifice 72 hours later. Results: Administration of Angiopeptin (2 to 200 μg/kg/day) significantly reduced intimal thickening by approximately 50% in all three vessels when evaluated 3 weeks after injury. This inhibitory effect was unrelated to duration of treatment and dose. Treatment initiated at the time of injury was found to be effective, but delaying treatment for 8, 18, or 27 hours abrogated the inhibitory effect of Angiopeptin on myointimal thickening. Angiopeptin treatment significantly decreased thymidine-labeled muclei of smooth muscle cells in vitro. Angiopeptin treatment similarly inhibited thymidine uptake in vitro by balloon-injured aorta segments. Conclusion: Angiopeptin significantly inhibits myointimal thickening by inhibiting vascular cell proliferation. Administration of Angiopeptin for 2 days is as efficacious as 3 weeks treatment in inhibiting myointimal thickening. Delaying treatment for as little as 8 hours after injury abrogates the inhibitory effects of Angiopeptin. This speaks to the importance of early events immediately after vascular tissue injury, suggesting that Angiopeptin inhibits the expression of early genes causally related to the vascular injury response and thereby triggering vascular cell proliferation. (J VASC SURG 1994;19:1084–91.)

  • Angiopeptin inhibition of myointimal hyperplasia after balloon angioplasty of large arteries in hypercholesterolaemic rabbits
    Clinical Science, 1993
    Co-Authors: Marcus H Howell, Marie L. Foegh, Michael M Adams, Mary S Wolfe, Peter W Ramwell
    Abstract:

    1. Currently, a wide range of drugs is being evaluated for the ability to prevent the restenosis which frequently accompanies percutaneous transluminal coronary angioplasty. Patients undergoing angioplasty are generally hypercholesterolaemic and therefore the possibility that plasma lipids may compromise the efficacy of anti-restenotic drugs must be assessed. A promising drug in several clinical trials for the prevention of restenosis is Angiopeptin, an octapeptide analogue of somatostatin that possesses a highly lipophilic terminal. 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. The degree of subsequent myointimal thickening was measured by morphometry. 3. Angiopeptin (20 micrograms day-1 kg-1) significantly inhibited myointimal thickening by an average of 47% in the infrarenal aorta and both the common and external iliac arteries in the presence of elevated plasma lipids concentrations. Low dose Angiopeptin (2 micrograms day-1 kg-1) significantly inhibited myointimal thickening in the external iliac artery but not in the other two vessels. 4. Angiopeptin treatment (20 micrograms day-1 kg-1) did not significantly modify the plasma cholesterol, very-low-density lipoprotein, intermediate-sized low-density lipoprotein, low-density lipoprotein and high-density lipoprotein concentrations that were elevated by the 0.5% cholesterol diet. 5. We conclude that the inhibitory effect of Angiopeptin is largely unaffected by elevated plasma lipid concentrations and that this drug did not modify plasma lipid concentrations in rabbits.

  • Angiopeptin in experimental models of restenosis
    Developments in cardiovascular medicine, 1993
    Co-Authors: Kenneth M Kent, Marie L. Foegh, Mun K Hong, Peter W Ramwell
    Abstract:

    Recurrent arterial obstructions, restenosis, after coronary angioplasty are due to myointimal proliferation, probably due to the barotrauma of balloon dilatation. This phenomenon has been studied extensively and although agents have been found to inhibit the response in experimental animal angioplasty, no agents have been proved to be useful in humans. The mitogenic response which leads to proliferation is undoubtably controlled by growth factors initiated by the initial arterial wall injury. Angiopeptin, a synthetic octapeptide analogue of somatastatin, is effective in inhibiting myointimal proliferation in a variety of animal models of vascular injury. Both in vitro and in vivo models of injury have demonstrated decreased intimai proliferation by morphometric analyses and decreased thymidine incorporation as an index of cellular proliferation. Physiologic amounts of these agents have been used in these experiments, doses that are well tolerated in humans. A controlled clinical trial is underway to assess the effectiveness of Angiopeptin on the restenosis that occurs after coronary angioplasty in humans. The trial will be completed in 1992.

  • peptide inhibition of myointimal proliferation by Angiopeptin a somatostatin analogue
    Journal of the American College of Cardiology, 1991
    Co-Authors: Connor Lundergan, Marie L. Foegh, Peter W Ramwell
    Abstract:

    Abstract Vascular smooth muscle cell hyperplasia is a major component of atherogenesis in various animal models. 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. Angiopeptin does not affect serum lipid profiles in nonhuman primates. It is unlikely, therefore, that its antiproliferative effect is mediated by alterations in cholesterol metabolism. Angiopeptin and other peptide analogues of somatostatin are potent inhibitors of growth hormone release and insulin-like growth factor-1 production. However, inhibition of smooth muscle cell proliferation in vivo is not a property common to all somatostatin analogues. This suggests that plasma growth hormone and growth hormone-dependent insulin-like growth factor-1 production are not physiologic stimuli for myointimal proliferation in vivo. Angiopeptin inhibits 3 H-thymidine incorporation into rat carotid artery explants, suggesting a local effect on automne or paracrine mechanisms regulating cell growth. 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.

Mun K Hong - One of the best experts on this subject based on the ideXlab platform.

  • first human experience with Angiopeptin eluting stent a quantitative coronary angiography and three dimensional intravascular ultrasound study
    Catheterization and Cardiovascular Interventions, 2005
    Co-Authors: Onhing Kwok, Mun K Hong, Winghing Chow, Tinchu Law, Alex Chiu, Waifat Lam, Jeffrey J Popma
    Abstract:

    Angiopeptin has been shown to reduce in-stent restenosis in various animal models. Meanwhile, BiodivYsio DD phosphorylcholine (PC)-coated stent provides a platform for local delivery of antiproliferative agents to the coronary artery. We studied the feasibility, safety, and impact on tissue growth of Angiopeptin-eluting BiodivYsio DD PC-coated stents in human native de novo coronary lesions. We enrolled 14 patients (16 lesions) who underwent intravascular ultrasound (IVUS)-guided Angiopeptin-eluting stent implantation in native coronary arteries between 3.0 and 4.0 mm in diameter with lesion length ≤ 18 mm. We successfully implanted 13 stents loaded with 22 μg of Angiopeptin and three stents with 126 μg of Angiopeptin. No major adverse cardiac events or target vessel failure occurred at 1-year clinical follow-up. All patients underwent 6-month angiographic and volumetric IVUS follow-up. In-stent late loss was 0.46 ± 0.32 mm in the low-dose group and 0.26 ± 0.14 mm in the high-dose group. Binary restenosis rate was 0%. Follow-up percentage neointimal hyperplasia by IVUS was 18.4% ± 22.5% for the low-dose group and 10.2% ± 5.8% for the high-dose group, respectively. There were no edge effect and late stent malapposition. Angiopeptin-eluting BiodivYsio DD PC stent appears feasible and safe in treating native de novo coronary lesions with modest degree of neointimal hyperplasia. © 2005 Wiley-Liss, Inc.

  • single dose intramuscular administration of sustained release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Coronary Artery Disease, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Ran Kornowski, Orville Bramwell, Seedabarum S Cathapermal, Martin B Leon
    Abstract:

    BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. METHODS: Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). RESULTS: A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. CONCLUSIONS: This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

  • continuous subcutaneous Angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Circulation, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Seedabarum S Cathapermal, Roxana Mehran, Gary S Mintz, Chiu S Wong, Martin B Leon
    Abstract:

    Background In-stent restenosis results primarily from neointimal hyperplasia. 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. Methods and Results Forty pigs were randomly assigned to one of four groups (n=10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 μg Angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 μg/kg total dose), and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent dia...

  • the effect of porous infusion balloon delivered Angiopeptin on myointimal hyperplasia after balloon injury in the rabbit
    Circulation, 1993
    Co-Authors: Mun K Hong, Ml Foegh, P W Ramwell, Tahira Bhatti, B J Matthews, K S Stark, S S Cathapermal, Kenneth M Kent
    Abstract:

    BACKGROUND Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of Angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied. METHODS AND RESULTS Three rabbits received 125I-Angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three Angiopeptin groups receiving 1, 10, or 100 micrograms/mL of Angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the Angiopeptin groups compared with the control group. 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). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the Angiopeptin-treated animals, endothelial cells were present at both locations. CONCLUSIONS 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.

  • Angiopeptin in experimental models of restenosis
    Developments in cardiovascular medicine, 1993
    Co-Authors: Kenneth M Kent, Marie L. Foegh, Mun K Hong, Peter W Ramwell
    Abstract:

    Recurrent arterial obstructions, restenosis, after coronary angioplasty are due to myointimal proliferation, probably due to the barotrauma of balloon dilatation. This phenomenon has been studied extensively and although agents have been found to inhibit the response in experimental animal angioplasty, no agents have been proved to be useful in humans. The mitogenic response which leads to proliferation is undoubtably controlled by growth factors initiated by the initial arterial wall injury. Angiopeptin, a synthetic octapeptide analogue of somatastatin, is effective in inhibiting myointimal proliferation in a variety of animal models of vascular injury. Both in vitro and in vivo models of injury have demonstrated decreased intimai proliferation by morphometric analyses and decreased thymidine incorporation as an index of cellular proliferation. Physiologic amounts of these agents have been used in these experiments, doses that are well tolerated in humans. A controlled clinical trial is underway to assess the effectiveness of Angiopeptin on the restenosis that occurs after coronary angioplasty in humans. The trial will be completed in 1992.

Kenneth M Kent - One of the best experts on this subject based on the ideXlab platform.

  • single dose intramuscular administration of sustained release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Coronary Artery Disease, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Ran Kornowski, Orville Bramwell, Seedabarum S Cathapermal, Martin B Leon
    Abstract:

    BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. METHODS: Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). RESULTS: A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. CONCLUSIONS: This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

  • continuous subcutaneous Angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in stent restenosis model
    Circulation, 1997
    Co-Authors: Mun K Hong, Marie L. Foegh, Kenneth M Kent, Fermin O Tio, Seedabarum S Cathapermal, Roxana Mehran, Gary S Mintz, Chiu S Wong, Martin B Leon
    Abstract:

    Background In-stent restenosis results primarily from neointimal hyperplasia. 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. Methods and Results Forty pigs were randomly assigned to one of four groups (n=10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 μg Angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 μg/kg total dose), and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent dia...

  • the effect of porous infusion balloon delivered Angiopeptin on myointimal hyperplasia after balloon injury in the rabbit
    Circulation, 1993
    Co-Authors: Mun K Hong, Ml Foegh, P W Ramwell, Tahira Bhatti, B J Matthews, K S Stark, S S Cathapermal, Kenneth M Kent
    Abstract:

    BACKGROUND Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of Angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied. METHODS AND RESULTS Three rabbits received 125I-Angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three Angiopeptin groups receiving 1, 10, or 100 micrograms/mL of Angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the Angiopeptin groups compared with the control group. 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). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the Angiopeptin-treated animals, endothelial cells were present at both locations. CONCLUSIONS 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.

  • Angiopeptin in experimental models of restenosis
    Developments in cardiovascular medicine, 1993
    Co-Authors: Kenneth M Kent, Marie L. Foegh, Mun K Hong, Peter W Ramwell
    Abstract:

    Recurrent arterial obstructions, restenosis, after coronary angioplasty are due to myointimal proliferation, probably due to the barotrauma of balloon dilatation. This phenomenon has been studied extensively and although agents have been found to inhibit the response in experimental animal angioplasty, no agents have been proved to be useful in humans. The mitogenic response which leads to proliferation is undoubtably controlled by growth factors initiated by the initial arterial wall injury. Angiopeptin, a synthetic octapeptide analogue of somatastatin, is effective in inhibiting myointimal proliferation in a variety of animal models of vascular injury. Both in vitro and in vivo models of injury have demonstrated decreased intimai proliferation by morphometric analyses and decreased thymidine incorporation as an index of cellular proliferation. Physiologic amounts of these agents have been used in these experiments, doses that are well tolerated in humans. A controlled clinical trial is underway to assess the effectiveness of Angiopeptin on the restenosis that occurs after coronary angioplasty in humans. The trial will be completed in 1992.