E-Selectin Blockade Decreases Adventitial Inflammation and Attenuates Intimal Hyperplasia in Rat Carotid Arteries After Balloon Injury

Introduction: Balloon angioplasty is a commonly applied procedure for treating atherosclerotic vascular diseases. However, the maintenance of long-term lumen patency is relatively difficult due to the occurrence of restenosis. Previous research has shown that the occurrence of vascular wall inflammation is associated with higher rates of restenosis. Sophocarpine (SPC) can exert various therapeutic effects such as anti-oxidation, anti-inflammation, anti-tumor, antivirus and immune regulation. This study aimed to investigate whether SPC can alleviate intimal hyperplasia following balloon injury in a rat carotid artery model. Methods: Twenty Sprague–Dawley rats were randomly assigned to four groups: (i) control, (ii) balloon injury, (iii) balloon injury followed by saline injection, and (iv) balloon injury followed by SPC administration. Each group contained five rats. A high-pressure balloon of 3 mm × 20 mm was placed in the carotid artery. The balloon was inflated to a pressure of 8 atmospheres to carry out rat carotid artery balloon injury model. The areas of neointimal and media were determined by Verhoeff_Van Gieson staining, and the intima-to-media (I:M) ratios were subsequently evaluated. After that, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, VCAM-1, ICAM-1 and eNOS were measured. Results: The ratio of I:M was remarkably higher in the balloon injury group than in the control group (p < 0.01). SPC could significantly decrease the ratio of I:M compared with the balloon injury group (p < 0.01). Besides, the protein levels of IL-6, IL-1β, MCP-1, NF-κB, TNF-α, ICAM-1 and VCAM-1 were increased in rat carotid arteries exposed to balloon injury (p < 0.01), and treatment with SPC could attenuate these effects (p < 0.05). Furthermore, balloon injury inhibited the protein expression of eNOS (p < 0.01), and SPC could elevate its level (p < 0.05). Conclusions: SPC could alleviate an intimal hyperplasia in balloon-injured carotid artery, and the mechanisms underlying this protective effect might be due to its inhibitory potency against inflammation signals. Our study also implies the potential applicability of SPC in treating restenosis after balloon angioplasty.

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Janus Kinase 3 Deficiency Promotes Vascular Reendothelialization

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316293 ◽

2021 ◽

Author(s):

Yung-Chun Wang ◽

Dunpeng Cai ◽

Xiao-Bing Cui ◽

Ya-Hui Chuang ◽

William P. Fay ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Injury ◽

Intimal Hyperplasia ◽

Carotid Arteries ◽

Muscle Cells ◽

Janus Kinase ◽

Balloon Injury ◽

Janus Kinase 3

Objective: The objective of this study is to determine the role of JAK3 (Janus kinase 3) in reendothelialization after vascular injury. Methods and Results: By using mouse carotid artery wire injury and rat balloon injury model, we found that JAK3 regulates reendothelialization and endothelial cell proliferation after vascular injury. JAK3 and phospho-JAK3 levels were increased in neointimal smooth muscle cells in response to vascular injury in mice. JAK3 deficiency dramatically attenuated the injury-induced intimal hyperplasia in carotid arteries of both male and female mice. Importantly, JAK3 deficiency caused an increased rate of reendothelialization following mechanical injury. Likewise, knockdown of JAK3 in medial smooth muscle cells elicited an accelerated reendothelialization with reduced intimal hyperplasia following balloon injury in rat carotid arteries. Interestingly, knockdown of JAK3 restored the expression of smooth muscle cell contractile protein smooth muscle α-actin in injury-induced intimal smooth muscle cells while increased the proliferating endothelial cells in the intima area. Conclusions: Our results demonstrate a novel role of JAK3 in the regeneration of endothelium after vascular injury, which may provide a new strategy to enhance reendothelialization while suppressing neointimal formation for effective vascular repair from injury.

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609. Delivery of p27 to Rat Carotid Arteries Using Electroporation Protects from Intimal Hyperplasia Following Balloon Injury

Molecular Therapy ◽

10.1016/s1525-0016(16)41051-8 ◽

2003 ◽

Vol 7 (5) ◽

pp. S237

Keyword(s):

Intimal Hyperplasia ◽

Carotid Arteries ◽

Balloon Injury

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Truncated YY1 interacts with BASP1 through a 339KLK341 motif in YY1 and suppresses vascular smooth muscle cell growth and intimal hyperplasia after vascular injury

Cardiovascular Research ◽

10.1093/cvr/cvab021 ◽

2021 ◽

Author(s):

Fernando S Santiago ◽

Yue Li ◽

Ling Zhong ◽

Mark J Raftery ◽

Laurence Lins ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Intimal Hyperplasia ◽

Carotid Arteries ◽

Neointima Formation ◽

Balloon Injury ◽

And Migration ◽

Proliferation And Migration

Abstract Aims In-stent restenosis and late stent thrombosis are complications associated with the use of metallic and drug-coated stents. Strategies that inhibit vascular smooth muscle cell (SMC) proliferation without affecting endothelial cell (EC) growth would be helpful in reducing complications arising from percutaneous interventions. SMC hyperplasia is also a pathologic feature of graft stenosis and fistula failure. Our group previously showed that forced expression of the injury-inducible zinc finger (ZNF) transcription factor, yin yang-1 (YY1), comprising 414 residues inhibits neointima formation in carotid arteries of rabbits and rats. YY1 inhibits SMC proliferation without affecting EC growth in vitro. Identifying a shorter version of YY1 retaining cell-selective inhibition would make it more amenable for potential use as a gene therapeutic agent. Methods and results We dissected YY1 into a range of shorter fragments (YY1A-D, YY1Δ) and found that the first two ZNFs in YY1 (construct YY1B, spanning 52 residues) repressed SMC proliferation. Receptor binding domain analysis predicts a three-residue (339KLK341) interaction domain. Mutation of 339KLK341 to 339AAA341 in YY1B (called YY1Bm) abrogated YY1B’s ability to inhibit SMC but not EC proliferation and migration. Incubation of recombinant GST-YY1B and GST-YY1Bm with SMC lysates followed by precipitation with glutathione–agarose beads and mass spectrometric analysis identified a novel interaction between YY1B and BASP1. Overexpression of BASP1, like YY1, inhibited SMC but not EC proliferation and migration. BASP1 siRNA partially rescued SMC from growth inhibition by YY1B. In the rat carotid balloon injury model, adenoviral overexpression of YY1B, like full-length YY1, reduced neointima formation, whereas YY1Bm had no such effect. CD31+ immunostaining suggested YY1B could increase re-endothelialization in a 339KLK341-dependent manner. Conclusion These studies identify a truncated form of YY1 (YY1B) that can interact with BASP1 and inhibit SMC proliferation, migration, and intimal hyperplasia after balloon injury of rat carotid arteries as effectively as full length YY1. We demonstrate the therapeutic potential of YY1B in vascular proliferative disease.

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Diet-Induced Hyperhomocysteinemia Exacerbates Neointima Formation in Rat Carotid Arteries After Balloon Injury

Circulation ◽

10.1161/01.cir.103.1.133 ◽

2001 ◽

Vol 103 (1) ◽

pp. 133-139 ◽

Cited By ~ 66

Author(s):

Hiroyuki Morita ◽

Hiroki Kurihara ◽

Shigetaka Yoshida ◽

Yuichiro Saito ◽

Takayuki Shindo ◽

...

Keyword(s):

Carotid Arteries ◽

Neointima Formation ◽

Balloon Injury

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Effect of gene delivery of NOS isoforms on intimal hyperplasia and endothelial regeneration after balloon injury

Gene Therapy ◽

10.1038/sj.gt.3302882 ◽

2006 ◽

Vol 14 (5) ◽

pp. 396-404 ◽

Cited By ~ 49

Author(s):

R Cooney ◽

S O Hynes ◽

F Sharif ◽

L Howard ◽

T O'Brien

Keyword(s):

Gene Delivery ◽

Intimal Hyperplasia ◽

Balloon Injury ◽

Endothelial Regeneration ◽

Nos Isoforms

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Fibronectin Incorporation into Extracellular Matrix of Rat Carotid Arteries After Balloon Injury

Journal of Vascular and Interventional Radiology ◽

10.1016/s1051-0443(98)70378-1 ◽

1998 ◽

Vol 9 (4) ◽

pp. 710-711

Author(s):

Claude Roland ◽

Darren E. MacNaughton ◽

Dhiraj Shah ◽

Peter Vincent ◽

Paul Kreienberg

Keyword(s):

Extracellular Matrix ◽

Carotid Arteries ◽

Balloon Injury

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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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