ANIMAL AND IN VITRO MODELS IN HUMAN DISEASESDifferent inflammatory response and oxidative stress in neointimal hyperplasia after balloon angioplasty and stent implantation in cholesterol-fed rabbits
Introduction
Restenosis after percutaneous coronary interventions (PCI) is an important clinical issue because large numbers of coronary interventions are required, and their indication is expanding. Although the use of drug-eluting stent dramatically reduced the incidence of restenosis, restenosis still remains a crucial problem [4]. Restenosis after balloon angioplasty is considered to arise through a combination of inadequate or deleterious arterial remodeling and neointimal hyperplasia, whereas in-stent restenosis arises primarily from neointimal hyperplasia [28], [31]. Increasing evidence from both clinical and animal studies indicates that inflammation plays a pivotal role in restenosis after both types of intervention [12].
C-reactive protein (CRP) is an acute phase protein that can serve as a marker of inflammation. In prospective epidemiologic studies, plasma levels of CRP predict future cardiovascular events [32], and recent clinical studies indicate that this protein is also a predictor of restenosis after PCI [2], [6]. We have previously reported that positive immunostaining for CRP in initial culprit lesions could predict the outcome of directional coronary atherectomy (DCA) [17], and CRP was more involved in the pathogenesis of in-stent restenosis than in that of restenosis after DCA [21]. In addition, CRP has a pro-oxidative effect [23], and oxidation is implicated in atherogenesis and restenosis after PCI [3], [38]. These lines of evidence suggest that CRP and oxidized lipoprotein are directly involved in the development of restenotic lesions. However, expression and localization of these molecules in restenotic lesions has not been well examined.
The present study investigated the synthesis of CRP, the localization of CRP and oxidized lipoprotein in neointimal hyperplasia after balloon injury and stent implantation in hyperlipidemic rabbits, and furthermore examined the effects of anti-oxidant probucol on neointimal growth and the inflammatory response.
Section snippets
Balloon injury and stenting protocol
In this study, 24 male Japanese White rabbits (weight 3.1–3.3 kg) were used in research protocols that were approved by the Animal Care Committee of the University of Miyazaki (No. 2003-011). All animals received humane care according to the Guide for the Care and Use of Laboratory Animals, prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1996).
The rabbits were randomly separated into Group C (),
Serum concentrations of TC, LDL-C, TG, and lipid peroxide
Table 1 shows the serum concentrations of TC, LDL-C, TG, and TBARS. These levels, except for TBARS of Group P, increased with time at 2, 4, and 8 weeks in both groups. Values of TC, LDL-C, and TG were lower in Group P than in Group C, but were not statistically significant. The TBARS level was significantly lower in Group P than in Group C. The weights of both groups of rabbits increased similarly (data not shown).
Luminal stenosis after balloon injury and stent implantation
Angiographs of rabbit iliac arteries obtained 8 weeks after balloon injury (right
Discussion
The present study demonstrates that the inflammatory response during neointimal development differs after balloon injury and stent implantation. In addition, although the anti-oxidant prevented the development of stenosis after both types of vascular injury in the hyperlipidemic rabbits, it was more effective after stenting.
Restenosis is the process of luminal narrowing in an atherosclerotic artery after intervention, such as balloon angioplasty and stenting. Increasing evidence indicates that
Acknowledgements
This study was supported in part by Grants-in-Aid for Scientific Research (c) (No. 15590305, 16590284) and for the 21st COE Research (Life Science) from the Ministry of Education, Science, Sports, and Culture, Japan.
References (45)
- et al.
C-reactive protein-induced upregulation of extracellular matrix metalloproteinase inducer in macrophages: inhibitory effect of fluvastatin
Life Sci.
(2006) - et al.
Increased C-reactive protein levels in patients with in-stent restenosis and its implications
Am. J. Cardiol.
(2001) - et al.
A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents
Lancet
(2004) - et al.
Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty
J. Am. Coll. Cardiol.
(1999) - et al.
Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART])
Am. J. Cardiol.
(2000) - et al.
Effect of BO-653 and probucol on c-MYC and PDGF-A messenger RNA of the iliac artery after balloon denudation in cholesterol-fed rabbits
Atherosclerosis
(2002) - et al.
Involvement of C-reactive protein obtained by directional coronary atherectomy in plaque instability and developing restenosis in patients with stable or unstable angina pectoris
Am. J. Cardiol.
(2003) - et al.
Possible contribution of C-reactive protein within coronary plaque to increasing its own plasma levels across coronary circulation
Am. J. Cardiol.
(2004) - et al.
A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions: complex formation of oxidized phosphatidylcholines and polypeptides
J. Biol. Chem.
(1994) - et al.
Relation of C-reactive protein to restenosis after coronary stent implantation and to restenosis after coronary atherectomy
Am. J. Cardiol.
(2004)
Regulation of complement activation by C-reactive protein
Immunopharmacology
Mechanisms of restenosis after coronary intervention: difference between plain old balloon angioplasty and stenting
Cardiovasc. Pathol.
Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits
Atherosclerosis
C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance
Am. J. Pathol.
Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty
Am. Heart J.
Generation of C-reactive protein and complement components in atherosclerotic plaques
Am. J. Pathol.
Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial
J. Am. Coll. Cardiol.
Oxidative stress as a signaling mechanism of the vascular response to injury: the redox hypothesis of restenosis
Cardiovasc. Res.
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions
J. Clin. Invest.
Effects of probucol on vascular remodeling after coronary angioplasty. Multivitamins and Probucol Study Group
Circulation
Pathology of acute and chronic coronary stenting in humans
Circulation
Morphological predictors of restenosis after coronary stenting in humans
Circulation
Cited by (21)
Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity
2021, AtherosclerosisCitation Excerpt :An angioplasty balloon catheter (diameter, 2.5 mm; length, 9 mm; QUANTUM, Boston Scientific, Galway, Ireland) was inserted into each iliac artery via the bilateral femoral arteries under fluoroscopic guidance. The catheter was inflated at 12 atm and retracted three times to denude the endothelium [14]. The standard chow diet was maintained, and stenting or sham procedure was performed 4 weeks post-balloon injury.
Hypercholesterolemia and oxidative stress inhibit endothelial cell healing after arterial injury
2012, Journal of Vascular SurgeryCitation Excerpt :Increased oxidative stress has been demonstrated in humans following an after arterial injury, specifically a coronary angioplasty.32 The inflammatory response and oxidative stress after stent placement is greater than after balloon angioplasty alone, perhaps due to the presence of a foreign body and is accompanied by a greater accumulation of oxidized lipids.33 These multiple sources of oxidative stress may adversely impact EC healing in the clinical setting.
Oxidative stress changes after stent implantation: A randomized comparative study of sirolimus-eluting and bare metal stents
2010, International Journal of CardiologyCitation Excerpt :Indeed, previous studies showed that the inflammatory response after stent implantation further enhances oxidative stress in the growing lesions, while on the other hand oxidative stress, which has proinflammatory properties, could cause inflammation [6,7]. Regardless of the cause, previous studies have shown that the increase in oxidative stress seen after stent implantation can induce a chain reaction conducive to neointimal formation and vascular remodeling, which may lead to neoangiogenesis and restenosis [8–10]. SES have come onto the scene in recent years.
Hemin prevents in-stent stenosis in rat and rabbit models by inducing heme-oxygenase-1
2010, Journal of Vascular SurgeryCitation Excerpt :Using the rat aorta stenting model, we further investigated the cellular mechanisms underlying the protective effect of hemin. Inflammatory responses and apoptosis have been recognized to be involved in the early events of stenosis.20-22 We observed that hemin prevented early inflammatory response, in agreement with its well known anti-inflammatory effect.23
Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits
2008, Journal of Vascular Surgery2-Methoxyestradiol inhibits carotid artery intimal hyperplasia induced by balloon injury via inhibiting JAK/STAT axis in rats
2022, Environmental Science and Pollution Research