Effect of Intravascular Irradiation on Cell Proliferation, Apoptosis, and Vascular Remodeling After Balloon Overstretch Injury of Porcine Coronary Arteries

Waksman, Ron; Rodríguez, José Carlos del Castillo; Robinson, Keith A.; Cipolla, Gustavo D.; Crocker, Ian; Scott, Neal A.; King, Spencer B.; Wilcox, Josiah N.

doi:10.1161/01.cir.96.6.1944

Cited by 159 publications

(70 citation statements)

References 43 publications

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“…41 However, after ␥-RT, there was no significant decrease in SMC numbers, and therefore, few apoptotic cells were identified. These observations match previous findings in an in vivo study, wherein no significant differences in the percentage of TUNEL-positive cells in irradiated porcine coronary vessels were found up to 7 days after balloon angioplasty, 42 compared with uninjured arteries.…”

Section: Discussionsupporting

confidence: 91%

Different Effects of Photodynamic Therapy and γ-Irradiation on Vascular Smooth Muscle Cells and Matrix

Heckenkamp

Leszczyński

Schiereck

et al. 1999

ATVB

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Abstract-␥-Irradiation (␥-RT) and photodynamic therapy (PDT) are known to inhibit intimal hyperplasia. The common mechanism is that both modalities produce free radicals, but unlike ␥-RT, PDT generates them through the absorption of light by photosensitizers. The purpose of this in vitro study was to assess the differences that PDT and ␥-RT have on the fibroproliferative response after vascular injury by comparing their effects on vascular smooth muscle cells (SMCs) and on the extracellular matrix (ECM). Mitochondrial activity (tetrazolium salt), proliferation ([ 3 H]thymidine incorporation), and the mechanisms of cell death (terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling [TUNEL] staining) were used to assess differences between PDT (100 J/cm 2 ) and ␥-RT (10 or 20 Gy) on SMC injury. The different effects on bioregulatory molecules were investigated by quantitating the proliferation of SMCs cultured with conditioned medium and on treated ECM. PDT of SMCs reduced proliferation and mitochondrial activity (0.5Ϯ0.75% and 1.7Ϯ4.25%, respectively, PϽ0.0001), whereas ␥-RT of SMCs decreased cell proliferation but did not affect metabolic activity. Stimulation with calf serum of ␥-RT-treated SMCs did not affect proliferation but increased mitochondrial enzyme activity (160Ϯ11%, PϽ0.0005). The conditioned medium, derived from PDT-but not ␥-RT-treated SMCs, did not stimulate effector SMC proliferation compared with ␥-RT-treated SMCs (16Ϯ4.1% versus 80Ϯ16.8%, PϽ0.0001). Apoptosis was the principle cytotoxic mechanism after PDT, whereas ␥-RT cells were growth arrested but viable. PDT of the ECM reduced effector SMC proliferation compared with controls and ␥-RT cells (18Ϯ6.5% versus 100Ϯ17.7% and 84Ϯ8.9%, respectively, PϽ0.0001). These data suggest that ␥-RT and PDT may inhibit restenosis but by different mechanisms. The effects of PDT are more diverse and may result in improved outcome while avoiding the teratogenic exposure due to ionizing irradiation. (Arterioscler Thromb Vasc Biol.

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Section: Discussionsupporting

confidence: 91%

Different Effects of Photodynamic Therapy and γ-Irradiation on Vascular Smooth Muscle Cells and Matrix

Heckenkamp

Leszczyński

Schiereck

et al. 1999

ATVB

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“…2,7 The lesser amount of neointima observed in the present study (13.6%) was comparable to the numbers reported for radioactive stents (7.4% to 16.7%) 8 and sirolimus-coated stents (10.4% to 11.0%). 4 Importantly, animal studies have demonstrated that the histological characteristics of paclitaxel-eluting stents are similar to those after intracoronary radiation therapy in several aspects, 3,9 which raises the concern of potentially increased late thrombosis rates and lumen narrowing in the vessel segments adjacent to the drug-eluting stent. In this initial experience with the QP2-eluting stent, however, late thrombotic events were not observed, although clinical trials with a larger study population will be required to confirm this preliminary result.…”

Section: Discussionmentioning

confidence: 99%

Novel Drug-Delivery Stent

Honda¹,

Grube²,

Fuente³

et al. 2001

Circulation

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Background-The aim of this study was to use serial intravascular ultrasound (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a taxane analogue) delivery on neointimal tissue growth within the stent and on vessel dimensions at the adjacent reference segments. Methods and Results-Serial IVUS analyses (immediately after intervention and at follow-up at 8.3 months) were performed in 15 native coronary lesions treated with the QuaDS-QP2 stent. IVUS measurements were performed at 8 cross-sections in each target segment (4 cross-sections within the stent and 2 cross-sections in each reference segment). At baseline, no significant plaque protrusion or thrombus was detected in the target segment. Mild incomplete stent apposition and edge dissection were observed in one and two cases, respectively. Percent expansion of the stent (minimum stent area/average reference lumen area) was 96.0Ϯ21.7%. At follow-up, mean neointimal area within the stent was 1.2Ϯ1.3 mm 2 , and mean cross-sectional narrowing (neointimal area/stent area) was 13.6Ϯ14.9%. At the vessel segments immediately adjacent to the stent, a significant increase in plaque area (1.9Ϯ2.6 mm 2 , Pϭ0.001) was observed, but vessel area remained unchanged. However, no patients showed clinically significant in-stent or edge restenosis (diameter stenosis Ն50%) during the follow-up period. Conclusions-The first human experience with the new drug-delivery stent showed a minimal amount of neointimal proliferation in the stented segment. Late lumen loss at the reference sites adjacent to the stent was acceptable and predominantly due to plaque proliferation.

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“…The growth of the vessel (+21.4±27.8 mm 3 ) observed after 180 days of treatment suggests that intracoronary beta radiation induced a positive remodeling of the arterial wall, characterized by an "accommodative" process of the plaque (correlation of the increase in the ∆ external elastic membrane vs D plaque, r=0.963, P < 0.01), preserving the volume of the in-stent lumen. Experimental data have suggested that radiation has an effect on the remodeling of the vessel, due to the change in cell response in the adventitia layer 33,34 . Positive remodeling, accommodating the neointimal growth after 6 months, has been shown on ultrasonographic analyses 35 , considering that other studies did not report changes in the total area of the vessel or of the plaque behind the stent 27 .…”

Section: Discussionmentioning

confidence: 99%

Braquiterapia intracoronariana. Tratamento da reestenose intra-stent com o sistema Beta-Cath: experiência inicial na América Latina

Muñoz

Feres

Abizaid

et al. 2004

Arq. Bras. Cardiol.

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Effect of Intravascular Irradiation on Cell Proliferation, Apoptosis, and Vascular Remodeling After Balloon Overstretch Injury of Porcine Coronary Arteries

Abstract: These studies suggest that intracoronary radiation primarily inhibits the first wave of cell proliferation in the vessel wall and demonstrates a favorable effect on late remodeling by preventing adventitial fibrosis at the injury site.

Cited by 159 publications

References 43 publications

Different Effects of Photodynamic Therapy and γ-Irradiation on Vascular Smooth Muscle Cells and Matrix

Different Effects of Photodynamic Therapy and γ-Irradiation on Vascular Smooth Muscle Cells and Matrix

Novel Drug-Delivery Stent

Braquiterapia intracoronariana. Tratamento da reestenose intra-stent com o sistema Beta-Cath: experiência inicial na América Latina

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