Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine

Strauss, Bradley H.; Wilson, Rachel; Houten, Rachel; Suylen, Robert Jan van; Murphy, Edward; Escaned, Javier; Verdouw, P. D.; Serruys, P. W.; Giessen, Willem J. van der

doi:10.1097/00019501-199407000-00012

Cited by 15 publications

(10 citation statements)

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“…Doxorubicin hydrochloride caused dose-related damage to the pulmonary endothelial cells and when used in higher doses resulted in endothelial necrosis (15). Mitomycin C delivered via a micropore balloon catheter failed to inhibit the formation of intimal hyperplasia and was associated with an increased amount of intimal hyperplasia in injured arterial segments (17). At concentrations similar to intravenously administered doses, mitomycin C is taken up by endothelial cells and is converted to the reactive form.…”

Section: Prevalence Of Hepatic Arterial Thrombosis and Hepatic Arterimentioning

confidence: 99%

Hepatic Arterial Complications in Liver Transplant Recipients Treated with Pretransplantation Chemoembolization for Hepatocellular Carcinoma

Richard

Silberzweig²,

Mitty³

et al. 2000

Radiology

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Section: Prevalence Of Hepatic Arterial Thrombosis and Hepatic Arterimentioning

confidence: 99%

Hepatic Arterial Complications in Liver Transplant Recipients Treated with Pretransplantation Chemoembolization for Hepatocellular Carcinoma

Richard

Silberzweig²,

Mitty³

et al. 2000

Radiology

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“…The inhibition of intimal thickening by MMc is independent of any overt signs of toxicity or with an increase in apoptosis, suggesting that vessel wall MMc levels were below the cytotoxic range. Of note, in one early study, 39 MMc failed to block neointima formation in balloon-injured rabbit iliac arteries. However, this study used only a single acute intramural infusion of MMc into the arterial wall, and the rate and extent of MMc penetration into the vessel wall was not determined.…”

Section: Discussionmentioning

confidence: 99%

Single Perivascular Delivery of Mitomycin C Stimulates p21 Expression and Inhibits Neointima Formation in Rat Arteries

Granada

Ensenat

Keswani

et al. 2005

ATVB

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Objective-Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. Methods and Results-Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 mol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 mol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G 2 /M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. Key Words: angioplasty Ⅲ arteries Ⅲ mitomycin C Ⅲ restenosis Ⅲ smooth muscle cells T he healing response to stent implantation starts immediately after injury, generally peaks at 2 weeks after the initial insult has occurred, and is mainly regulated by vascular smooth muscle cells (VSMCs). 1-3 Drug-eluting stents reduce restenosis by decreasing the formation of a neointima caused by excessive cellular activation after arterial injury. 4,5 The successful development of drug-eluting stents has relied on the controlled release of antiproliferative agents over several weeks to regulate the activation and proliferation of VSMCs. 4,5 Accordingly, potent antiproliferative agents have the potential of decreasing the degree of neointimal formation after stent implantation if cytostatic rather than cytotoxic tissue levels can be achieved at the site of injury. Conclusion-TheseMitomycin C (MMc) is an antibiotic agent with antiproliferative properties derived from the soil fungus Streptomyces caespitosus. 6 In addition to cancer therapy, 7 MMc is a well-recognized antifibroblastic drug. In vitro studies using cultured human fibroblasts have shown that after exposure to a single dose of MMc, there is a profound inhibition of the proliferative phase of the wound-healing response, specifically through the inhibition of fibroblast replication. 8 These findings have led to the successful clinical use of MMc as an adjuvant in procedures displaying excessive late-onset scar tissue formation, 8 -10 and suggest that MMc may be suitable as an agent to decrease neointima formation. Accordingly, we sought to evaluate the growth modulating potential of MMc on cultured rat arterial VSMCs and the impact of MMc on neointima formation in a rat model of arterial balloon injury. Methods MaterialsMMc was purchased from Henan Kangtai Pharmaceutical Group (Zh...

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“…Moreover, it has previously been shown that local delivery of mitomycin C had no favourable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. 16 As a result, the inhibition by GES of neointimal formation in the vessel could be related to immunocompatible granulation tissue over the metal stents, which could decrease the local inflammatory reaction in the vessels. This reaction has been proved to be a major contributor to in-stent restenosis.…”

Section: Discussionmentioning

confidence: 99%

“…16 Briefly, under anaesthesia, a 5F sheath (Cordis, Miami Lakes, Florida, USA) was placed in the right carotid artery. Heparin sulfate (1000 IU) and acetylsalicylic acid (50 mg) were injected intraarterially to prevent early arterial occlusion.…”

Section: Stenting In Eiamentioning

confidence: 99%

Granulation encapsulated stent: a new therapeutic approach for vascular implantation

Tang

Chen²,

Tang³

et al. 2005

Heart

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Objectives: To determine if stents could be encapsulated with immunocompatible granulation tissue for the treatment of vascular diseases. Methods: Bare metal stents were implanted in New Zealand white rabbits so they would be encapsulated with immunocompatible granulation tissue. The granulation encapsulated stents (GES) were then treated with either mitomycin C or saline, and implanted into rabbit iliac arteries for 4 weeks. To test whether the effect of mitomycin C was retained, we co-cultured smooth muscle cells for 3 h with subcutaneous tissue (as control) or with granulation tissue from GES treated with mitomycin C and saline. Results: Vessels with GES treated with mitomycin C (MS) and washed with saline had significantly less neointimal area (NA) after 4 weeks (0.27 (SD 0.03) mm 2 than vessels containing bare metal stents (B) (1.15 (SD 0.10) mm 2 , n = 5, p,0.05) or GES treated with saline (S) (4.78 (SD 0.72) mm 2 , n = 5, p,0.05). The average vessel injury score was not significantly different among these three groups (S: 1.98 (SD 0.51), MS: 1.46 (SD 0.18) and B: 1.51 (SD 0.32)). GES treated with saline had significantly less NA than the other two groups and also blocked blood flow in the contralateral iliac artery in the abdominal aortic bifurcation immediately after implantation and 4 weeks later. Histology also showed neointimal overgrowth in the vessel wall over the contralateral iliac artery. Conclusions: GES treated with mitomycin C can significantly inhibit neointimal formation in rabbit arteries due to the formation of granulation tissue. GES treated with saline demonstrated significantly increased NA and resisted normal rabbit artery pressures.

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Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine

Cited by 15 publications

References 0 publications

Hepatic Arterial Complications in Liver Transplant Recipients Treated with Pretransplantation Chemoembolization for Hepatocellular Carcinoma

Hepatic Arterial Complications in Liver Transplant Recipients Treated with Pretransplantation Chemoembolization for Hepatocellular Carcinoma

Single Perivascular Delivery of Mitomycin C Stimulates p21 Expression and Inhibits Neointima Formation in Rat Arteries

Granulation encapsulated stent: a new therapeutic approach for vascular implantation

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