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Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis

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Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis. / Wang, Dong; Deuse, Tobias; Stubbendorff, Mandy; Chernogubova, Ekaterina; Erben, Reinhold G; Eken, Suzanne M; Jin, Hong; Li, Yuhuang; Busch, Albert; Heeger, Christian-H; Behnisch, Boris; Reichenspurner, Hermann; Robbins, Robert C; Spin, Joshua M; Tsao, Philip S; Schrepfer, Sonja; Maegdefessel, Lars.

In: ARTERIOSCL THROM VAS, Vol. 35, No. 9, 09.2015, p. 1945-1953.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wang, D, Deuse, T, Stubbendorff, M, Chernogubova, E, Erben, RG, Eken, SM, Jin, H, Li, Y, Busch, A, Heeger, C-H, Behnisch, B, Reichenspurner, H, Robbins, RC, Spin, JM, Tsao, PS, Schrepfer, S & Maegdefessel, L 2015, 'Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis', ARTERIOSCL THROM VAS, vol. 35, no. 9, pp. 1945-1953. https://doi.org/10.1161/ATVBAHA.115.305597

APA

Wang, D., Deuse, T., Stubbendorff, M., Chernogubova, E., Erben, R. G., Eken, S. M., Jin, H., Li, Y., Busch, A., Heeger, C-H., Behnisch, B., Reichenspurner, H., Robbins, R. C., Spin, J. M., Tsao, P. S., Schrepfer, S., & Maegdefessel, L. (2015). Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis. ARTERIOSCL THROM VAS, 35(9), 1945-1953. https://doi.org/10.1161/ATVBAHA.115.305597

Vancouver

Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben RG, Eken SM et al. Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis. ARTERIOSCL THROM VAS. 2015 Sep;35(9):1945-1953. https://doi.org/10.1161/ATVBAHA.115.305597

Bibtex

@article{bbffafc298ba4423985aeb89fa3b0156,
title = "Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis",
abstract = "OBJECTIVE: Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) because of myointimal hyperplasia remains a major complication.APPROACH AND RESULTS: We investigated the regulatory role of microRNAs in myointimal hyperplasia/ISR, using a humanized animal model in which balloon-injured human internal mammary arteries with or without stenting were transplanted into Rowett nude rats, followed by microRNA profiling. miR-21 was the only significantly upregulated candidate. In addition, miR-21 expression was increased in human tissue samples from patients with ISR compared with coronary artery disease specimen. We systemically repressed miR-21 via intravenous fluorescein-tagged-locked nucleic acid-anti-miR-21 (anti-21) in our humanized myointimal hyperplasia model. As expected, suppression of vascular miR-21 correlated dose dependently with reduced luminal obliteration. Furthermore, anti-21 did not impede reendothelialization. However, systemic anti-miR-21 had substantial off-target effects, lowering miR-21 expression in liver, heart, lung, and kidney with concomitant increase in serum creatinine levels. We therefore assessed the feasibility of local miR-21 suppression using anti-21-coated stents. Compared with bare-metal stents, anti-21-coated stents effectively reduced ISR, whereas no significant off-target effects could be observed.CONCLUSION: This study demonstrates the efficacy of an anti-miR-coated stent for the reduction of ISR.",
keywords = "Animals, Antibodies, Antinuclear/pharmacology, Cell Proliferation/drug effects, Coated Materials, Biocompatible, Coronary Restenosis/genetics, Coronary Vessels/drug effects, Disease Models, Animal, Drug-Eluting Stents, Female, Gene Expression Regulation, Graft Occlusion, Vascular/genetics, Humans, Male, MicroRNAs/biosynthesis, Microscopy, Electron, Scanning, Middle Aged, Muscle, Smooth, Vascular/drug effects, Neointima/metabolism, Prosthesis Design, Rats, Rats, Nude",
author = "Dong Wang and Tobias Deuse and Mandy Stubbendorff and Ekaterina Chernogubova and Erben, {Reinhold G} and Eken, {Suzanne M} and Hong Jin and Yuhuang Li and Albert Busch and Christian-H Heeger and Boris Behnisch and Hermann Reichenspurner and Robbins, {Robert C} and Spin, {Joshua M} and Tsao, {Philip S} and Sonja Schrepfer and Lars Maegdefessel",
note = "{\textcopyright} 2015 American Heart Association, Inc.",
year = "2015",
month = sep,
doi = "10.1161/ATVBAHA.115.305597",
language = "English",
volume = "35",
pages = "1945--1953",
journal = "ARTERIOSCL THROM VAS",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

RIS

TY - JOUR

T1 - Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis

AU - Wang, Dong

AU - Deuse, Tobias

AU - Stubbendorff, Mandy

AU - Chernogubova, Ekaterina

AU - Erben, Reinhold G

AU - Eken, Suzanne M

AU - Jin, Hong

AU - Li, Yuhuang

AU - Busch, Albert

AU - Heeger, Christian-H

AU - Behnisch, Boris

AU - Reichenspurner, Hermann

AU - Robbins, Robert C

AU - Spin, Joshua M

AU - Tsao, Philip S

AU - Schrepfer, Sonja

AU - Maegdefessel, Lars

N1 - © 2015 American Heart Association, Inc.

PY - 2015/9

Y1 - 2015/9

N2 - OBJECTIVE: Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) because of myointimal hyperplasia remains a major complication.APPROACH AND RESULTS: We investigated the regulatory role of microRNAs in myointimal hyperplasia/ISR, using a humanized animal model in which balloon-injured human internal mammary arteries with or without stenting were transplanted into Rowett nude rats, followed by microRNA profiling. miR-21 was the only significantly upregulated candidate. In addition, miR-21 expression was increased in human tissue samples from patients with ISR compared with coronary artery disease specimen. We systemically repressed miR-21 via intravenous fluorescein-tagged-locked nucleic acid-anti-miR-21 (anti-21) in our humanized myointimal hyperplasia model. As expected, suppression of vascular miR-21 correlated dose dependently with reduced luminal obliteration. Furthermore, anti-21 did not impede reendothelialization. However, systemic anti-miR-21 had substantial off-target effects, lowering miR-21 expression in liver, heart, lung, and kidney with concomitant increase in serum creatinine levels. We therefore assessed the feasibility of local miR-21 suppression using anti-21-coated stents. Compared with bare-metal stents, anti-21-coated stents effectively reduced ISR, whereas no significant off-target effects could be observed.CONCLUSION: This study demonstrates the efficacy of an anti-miR-coated stent for the reduction of ISR.

AB - OBJECTIVE: Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) because of myointimal hyperplasia remains a major complication.APPROACH AND RESULTS: We investigated the regulatory role of microRNAs in myointimal hyperplasia/ISR, using a humanized animal model in which balloon-injured human internal mammary arteries with or without stenting were transplanted into Rowett nude rats, followed by microRNA profiling. miR-21 was the only significantly upregulated candidate. In addition, miR-21 expression was increased in human tissue samples from patients with ISR compared with coronary artery disease specimen. We systemically repressed miR-21 via intravenous fluorescein-tagged-locked nucleic acid-anti-miR-21 (anti-21) in our humanized myointimal hyperplasia model. As expected, suppression of vascular miR-21 correlated dose dependently with reduced luminal obliteration. Furthermore, anti-21 did not impede reendothelialization. However, systemic anti-miR-21 had substantial off-target effects, lowering miR-21 expression in liver, heart, lung, and kidney with concomitant increase in serum creatinine levels. We therefore assessed the feasibility of local miR-21 suppression using anti-21-coated stents. Compared with bare-metal stents, anti-21-coated stents effectively reduced ISR, whereas no significant off-target effects could be observed.CONCLUSION: This study demonstrates the efficacy of an anti-miR-coated stent for the reduction of ISR.

KW - Animals

KW - Antibodies, Antinuclear/pharmacology

KW - Cell Proliferation/drug effects

KW - Coated Materials, Biocompatible

KW - Coronary Restenosis/genetics

KW - Coronary Vessels/drug effects

KW - Disease Models, Animal

KW - Drug-Eluting Stents

KW - Female

KW - Gene Expression Regulation

KW - Graft Occlusion, Vascular/genetics

KW - Humans

KW - Male

KW - MicroRNAs/biosynthesis

KW - Microscopy, Electron, Scanning

KW - Middle Aged

KW - Muscle, Smooth, Vascular/drug effects

KW - Neointima/metabolism

KW - Prosthesis Design

KW - Rats

KW - Rats, Nude

U2 - 10.1161/ATVBAHA.115.305597

DO - 10.1161/ATVBAHA.115.305597

M3 - SCORING: Journal article

C2 - 26183619

VL - 35

SP - 1945

EP - 1953

JO - ARTERIOSCL THROM VAS

JF - ARTERIOSCL THROM VAS

SN - 1079-5642

IS - 9

ER -