Local Expression of Bovine Decorin by Cell-Mediated Gene Transfer Reduces Neointimal Formation After Balloon Injury in Rats

CGRP is a well-known neuropeptide that has various protective effects on cardiovascular system. Our previous studies have shown that CGRP inhibits vascular smooth muscle cell (VSMC) proliferation in vitro. The present study aimed to explore the role of the CGRP in neointimal formation after balloon injury in the rat aortic wall and the underlying mechanism. Gene transfer of CGRP was performed with the use of intramuscular electroporation in a balloon-injured rat aorta model. Apoptosis in VSMCs was determined by electrophoresis assessment of DNA fragmentation and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay. Overexpression of the CGRP gene significantly inhibited the neointimal formation after balloon injury compared with the mock transfer, as assessed by the intima-to-media ratio 14 days after balloon injury (29.2 ± 3.7% vs. 52.7 ± 5.4%; n = 9–12, P < 0.05). In addition, CGRP gene expression increased the number of apoptotic cells in the neointima in vivo 14 days after balloon injury. Similarly, the addition of bioactive CGRP and the nitric oxide donor induced similar apoptosis in cultured VSMCs. The antagonist of the CGRP1 receptor and inhibitors of cAMP-PKA and nitric oxide blocked CGRP-mediated apoptosis. Furthermore, CGRP gene transfer increased inducible nitric oxide synthase and p53 but decreased PCNA and Bcl-2 protein levels in balloon-injured rat aorta. Our data demonstrated that CGRP potently inhibited neointimal thickening in the rat aorta, at least in part through its distinct effects on apoptosis and proliferation of VSMCs both in vivo and in vitro. Therefore, delivery of the CGRP gene may have therapeutic implications in limiting vascular restenosis.

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Gene transfer of dominant negative Rho kinase suppresses neointimal formation after balloon injury in pigs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.278.6.h1744 ◽

2000 ◽

Vol 278 (6) ◽

pp. H1744-H1750 ◽

Cited By ~ 58

Author(s):

Yasuhiro Eto ◽

Hiroaki Shimokawa ◽

Junko Hiroki ◽

Kunio Morishige ◽

Tadashi Kandabashi ◽

...

Keyword(s):

Gene Transfer ◽

Rho Kinase ◽

Dominant Negative ◽

Balloon Injury ◽

Cellular Functions ◽

Neointimal Formation ◽

Stenotic Lesion ◽

Dominant Negative Form

Restenosis after angioplasty still remains a major problem for which neointimal formation appears to play an important role. Recent studies in vitro suggested that Rho kinase, a target protein of Rho, is important in various cellular functions. We thus examined whether Rho kinase is involved in the restenotic changes after balloon injury. In vivo gene transfer was performed immediately after balloon injury in both sides of the porcine femoral arteries with adenoviral vector encoding either a dominant negative form of Rho kinase (AdDNRhoK) or β-galactosidase (AdLacZ) as a control. One week after the transfer, immunohistochemistry confirmed the successful gene expression in the vessel wall, whereas 2 wk after the transfer, Western blotting showed the functional upregulation of Rho kinase at the AdLacZ site and its suppression at the AdDNRhoK site. Angiography showed the development of a stenotic lesion at the AdLacZ site where histological neointimal formation was noted, whereas those changes were significantly suppressed at the AdDNRhoK site. These results indicate that Rho kinase is involved in the pathogenesis of neointimal formation after balloon injury in vivo.

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Local Expression of C-Type Natriuretic Peptide Markedly Suppresses Neointimal Formation in Rat Injured Arteries Through an Autocrine/Paracrine Loop

Circulation ◽

10.1161/01.cir.96.7.2272 ◽

1997 ◽

Vol 96 (7) ◽

pp. 2272-2279 ◽

Cited By ~ 60

Author(s):

Hikaru Ueno ◽

Akihiro Haruno ◽

Nobuhiro Morisaki ◽

Mayumi Furuya ◽

Kenji Kangawa ◽

...

Keyword(s):

Natriuretic Peptide ◽

Neointimal Formation ◽

Local Expression

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Dihydroartemisinin ameliorates balloon injury‐induced neointimal formation in rats

Journal of Cellular Physiology ◽

10.1002/jcp.27809 ◽

2018 ◽

Vol 234 (7) ◽

pp. 11545-11554

Author(s):

Yang He ◽

Bei Sun ◽

Gang Chen ◽

Renping Huang

Keyword(s):

Balloon Injury ◽

Neointimal Formation

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Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon-injured arteries without bleeding complications

Cardiovascular Research ◽

10.1016/s0008-6363(99)00107-8 ◽

1999 ◽

Vol 43 (2) ◽

pp. 481-491 ◽

Cited By ~ 17

Author(s):

M Harada

Keyword(s):

Gene Transfer ◽

Bleeding Complications ◽

Neointimal Formation ◽

Prostacyclin Synthase

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Carotid Stent Restenosis and Thrombosis in Rabbits: The Effect of Antiplatelet Agents

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420931624 ◽

2020 ◽

Vol 25 (6) ◽

pp. 570-577

Author(s):

Nikolaos P. E. Kadoglou ◽

Marianna Stasinopoulou ◽

Triantafyllos Giannakopoulos ◽

Anastasios Papapetrou ◽

Constantinos Dimitriou ◽

...

Keyword(s):

High Fat Diet ◽

Carotid Arteries ◽

Antiplatelet Agents ◽

Balloon Injury ◽

Neointimal Formation ◽

Total Occlusion ◽

Stent Restenosis ◽

Vascular Walls ◽

New Zealand White Rabbits ◽

Group 3

Background: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits. Methods: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination. Results: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups ( P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups ( P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups ( P > .05). Conclusion: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.

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