RESUMO
Vascular lesions frequently arise as complication in patients diagnosed with diabetes mellitus (DM). Presently, percutaneous coronary intervention (PCI) and antithrombotic therapy serve as primary treatments. However, in-stent restenosis persists as a challenging clinical issue following PCI, lacking sustained and effective treatment. Linarin (LN) exhibits diverse pharmacological activities and is regarded as a potential drug for treating various diseases, including DM. But its specific role in restenosis after vascular injury in DM patients remains unclear. A rat model of diabetes-related restenosis was established to evaluate the role of LN on neointimal hyperplasia. Vascular smooth muscle cells (VSMCs) stimulated by high glucose (HG, 30 mM) underwent LN treatment. Additionally, an overexpression plasmid of A disintegrin and metalloproteinases (ADAM10) was constructed to transfect VSMCs. We employed CCK-8, Brdu, wound-healing scratch, and transwell migration assays to evaluate the proliferation and migration of VSMCs. Furthermore, western blot and immunofluorescence assays were utilized to investigate the expressions of ADAM10 and the downstream Notch signaling pathway in vivo and in vitro models. LN notably alleviated intimal hyperplasia after vascular injury in DM rats and reduced the protein expression of ADAM10, alongside its downstream Notch1 signaling pathway-related proteins (Notch1, NICD and Hes1) in rat carotid artery tissues. LN effectively suppressed the proliferation and migration of VSMCs induced by HG, downregulating the protein expression of ADAM10, Notch1, NICD and Hes1. Moreover, our findings indicated that ADAM10 overexpression significantly reversed LN's effects on proliferation, migration, and the expression of Notch1 signaling pathway-related proteins in HG-treated VSMCs. LN demonstrates potential therapeutic efficacy in addressing restenosis after diabetic-related vascular injury, with the ADAM10 mediated Notch signaling pathway playing a pivotal role.
Assuntos
Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide , Lesões das Artérias Carótidas , Movimento Celular , Proliferação de Células , Diabetes Mellitus Experimental , Proteínas de Membrana , Músculo Liso Vascular , Miócitos de Músculo Liso , Neointima , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Proteína ADAM10/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Músculo Liso Vascular/enzimologia , Movimento Celular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/enzimologia , Proliferação de Células/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Células Cultivadas , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/enzimologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Hiperplasia , Receptores Notch/metabolismo , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genética , Modelos Animais de Doenças , Ratos , Reestenose Coronária/patologia , Reestenose Coronária/etiologia , Reestenose Coronária/metabolismo , Reestenose Coronária/prevenção & controleRESUMO
The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT). In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70-80% (n = 119) and AS ≥ 80% (n = 85). Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidemia (odds ratio [OR], 4.754; 95% confidence interval [CI], 1.419-15.927, P = 0.011), neointimal rupture (OR: 3.640; 95% CI, 1.169-11.325, P = 0.026), red thrombus (OR: 4.482; 95% CI, 1.269-15.816, P = 0.020) and white thrombus (OR: 5.259; 95% CI, 1.660-16.659, P = 0.005). Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia, neointimal rupture, white thrombus and red thrombus were highly associated with and the progression of ISR lesions.
Assuntos
Reestenose Coronária , Vasos Coronários , Neointima , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Stents , Tomografia de Coerência Óptica , Humanos , Masculino , Feminino , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Pessoa de Meia-Idade , Idoso , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Estudos Retrospectivos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/patologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/patologia , Estenose Coronária/terapia , Ruptura EspontâneaRESUMO
PURPOSE: To establish an animal model for in-stent restenosis (ISR) after postthrombotic iliac vein stent placement and characterize histopathological changes in tissue within the stented vein. MATERIALS AND METHODS: Iliac vein thrombosis was induced using balloon occlusion and thrombin injection in 8 male Boer goats. Mechanical thrombectomy and iliac vein stent placement were performed 3 days after thrombosis induction. Restenosis was evaluated by venography and optical coherence tomography (OCT) at 1 and 8 weeks after stent placement, and stent specimens were taken for pathological examination after the animals were euthanized. RESULTS: Thrombosis induction was successful in all 8 goats, with >80% iliac vein occlusion. After thrombus removal, OCT revealed considerable venous intimal thickening and a small number of mural thrombi. Neointimal hyperplasia with thrombus formation was observed in all goats 1 week after stent implantation; the degree of ISR was 15%-33%. At 8 weeks, the degree of ISR was 21%-32% in 3 goats, and stent occlusion was observed in 1 goat. At 1 week, the neointima predominantly consisted of fresh thrombi. At 8 weeks, proliferplastic fibrotic tissue and smooth muscle cells (SMCs) were predominant, and the stent surfaces were endothelialized in 2 of 3 goats and partially endothelialized in 1 goat. CONCLUSIONS: In the goat model, postthrombotic neointimal hyperplasia in the venous stent may result from time-dependent thrombus formation and organization, accompanied by migration and proliferation of SMCs, causing ISR. These results provide a basis to further explore the mechanism of venous ISR and promote the development of venous stents that reduce neointimal hyperplasia.
Assuntos
Reestenose Coronária , Trombose Venosa , Animais , Masculino , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/cirurgia , Veia Ilíaca/patologia , Reestenose Coronária/patologia , Cabras , Hiperplasia/patologia , Stents , Neointima/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapiaRESUMO
BACKGROUND: Subjects with type 2 diabetes (T2D) have a higher risk of in-stent restenosis and stent thrombosis. The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been suggested to induce several effects on the vasculature that may reduce the risk of stent failure following an angioplasty. The aim of this study is to evaluate the effect of the GLP-1R agonist exenatide on endothelialization of a modern drug-eluting stent (DES) in subjects with T2D. METHODS: 38 subjects with T2D who were eligible for revascularization with implantation of DES were randomized to treatment with exenatide (once weekly) plus standard treatment, or to standard treatment alone. After 12 weeks, a new coronary angiography was performed to evaluate the percentage of strut coverage (primary endpoint) and the presence of neo-atherosclerosis by optical coherence tomography. This study was approved by the Stockholm's Ethical Review Board. RESULTS: The two groups were well balanced regarding baseline clinical characteristics. Strut coverage was 95% (88.7-98.5%) in the exenatide group and 91.4% (88.8-98.5%) in the control group (p = 0.692). There were no significant differences between groups neither in the thickness of neo-intima (0.2 mm in both groups, p = 0.471), nor the maximal in-stent obstruction by neo-intima (15.5% in exenatide group vs 14.7% in control group, p = 0.801). No significant differences were detected in the rate of target lesion revascularization between groups (p = 0.224). CONCLUSION: Twelve weeks treatment with exenatide did not lead to a significantly better stent coverage in people with T2D. No significant differences in the occurrence of neo-atherosclerosis were detected between groups. TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov (Rebuild Study, NCT02621489).
Assuntos
Diabetes Mellitus Tipo 2 , Exenatida , Intervenção Coronária Percutânea , Humanos , Aterosclerose/patologia , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Vasos Coronários/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Stents Farmacológicos , Exenatida/uso terapêutico , Stents , Tomografia de Coerência Óptica/métodos , Resultado do TratamentoAssuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Reestenose Coronária , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Vasos Coronários/patologia , Paclitaxel , Coração , Resultado do Tratamento , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/patologia , Reestenose Coronária/patologiaRESUMO
Neoatherosclerosis (NA) is a significant contributor to late stent failure; however, predictors of late in-stent restenosis (ISR) with NA have not been systematically reported. This study aimed to identify predictors of NA incidence and plaque vulnerability in patients with late ISR and the role of low-density lipoprotein cholesterol (LDL-C) levels in this process. A total of 216 patients with 216 lesions who underwent optical coherence tomography (OCT) before interventional procedure for late drug-eluting stent ISR were enrolled and divided into NA and non-NA groups based on OCT findings. Results showed that higher LDL-C levels were associated with NA, thin-cap fibroatheroma (TCFA), intimal disruption, plaque erosion, and thrombosis. Multivariate regression analysis revealed that the LDL-C level was an independent risk factor for NA and TCFA. The LDL-C levels exhibited a significant predictive value for NA and TCFA, surpassing other factors such as stent age and other lipid types. In conclusion, a high LDL-C level is an independent predictor of NA incidence and plaque vulnerability in patients with late ISR.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Reestenose Coronária , Stents Farmacológicos , Doenças das Valvas Cardíacas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patologia , Stents Farmacológicos/efeitos adversos , LDL-Colesterol , Tomografia de Coerência Óptica/métodos , Neointima , Valor Preditivo dos Testes , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Aterosclerose/patologia , Constrição Patológica/complicações , Doenças das Valvas Cardíacas/complicações , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/complicaçõesRESUMO
A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via in vivo imaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young's modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.
Assuntos
Reestenose Coronária , Estados Unidos , Humanos , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Vasos Coronários/patologia , Stents/efeitos adversos , Metais , Inflamação/complicações , Inflamação/patologiaRESUMO
Introduction: In-stent restenosis (ISR) is a major challenge in interventional cardiology. Both ISR and excessive skin healing are aberrant hyperplasic responses, which may be functionally related. However, the cellular component underlying ISR remains unclear, especially regarding vascular homeostasis. Recent evidence suggest that novel immune cell populations may be involved in vascular repair and damage, but their role in ISR has not been explored. The aims of this study is to analyze (i) the association between ISR and skin healing outcomes, and (ii) the alterations in vascular homeostasis mediators in ISR in univariate and integrative analyses. Methods: 30 patients with ≥1 previous stent implantation with restenosis and 30 patients with ≥1 stent without restenosis both confirmed in a second angiogram were recruited. Cellular mediators were quantified in peripheral blood by flow cytometry. Skin healing outcomes were analyzed after two consecutive biopsies. Results: Hypertrophic skin healing was more frequent in ISR patients (36.7%) compared to those ISR-free (16.7%). Patients with ISR were more likely to develop hypertrophic skin healing patterns (OR 4.334 [95% CI 1.044-18.073], p=0.033), even after correcting for confounders. ISR was associated with decreased circulating angiogenic T-cells (p=0.005) and endothelial progenitor cells (p<0.001), whereas CD4+CD28null and detached endothelial cells counts were higher (p<0.0001 and p=0.006, respectively) compared to their ISR-free counterparts. No differences in the frequency of monocyte subsets were found, although Angiotensin-Converting Enzyme expression was increased (non-classical: p<0.001; and intermediate: p<0.0001) in ISR. Despite no differences were noted in Low-Density Granulocytes, a relative increase in the CD16- compartment was observed in ISR (p=0.004). An unsupervised cluster analysis revealed the presence of three profiles with different clinical severity, unrelated to stent types or traditional risk factors. Conclusion: ISR is linked to excessive skin healing and profound alterations in cellular populations related to vascular repair and endothelial damage. Distinct cellular profiles can be distinguished within ISR, suggesting that different alterations may uncover different ISR clinical phenotypes.
Assuntos
Reestenose Coronária , Células Endoteliais , Humanos , Células Endoteliais/patologia , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Stents/efeitos adversos , FenótipoRESUMO
Percutaneous coronary intervention (PCI) is a management strategy for symptomatic obstructive coronary artery disease (CAD). Despite advancements, in-stent restenosis (ISR) still imparts a 1-2% annual rate of repeat revascularization-a focus of ongoing translational research. Optical coherence tomography (OCT) provides high resolution virtual histology of stents. Our study evaluates the use of OCT for virtual histological assessment of stent healing in a rabbit aorta model, enabling complete assessment of intraluminal healing throughout the stent. ISR varies based on intra-stent location, stent length, and stent type in a rabbit model-important considerations for translational experimental design. Atherosclerosis leads to more prominent ISR proliferation independent of stent-related factors. The rabbit stent model mirrors clinical observations, while OCT-based virtual histology demonstrates utility for pre-clinical stent assessment. Pre-clinical models should incorporate clinical and stent factors as feasible to maximize translation to clinical practice.
Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Intervenção Coronária Percutânea , Animais , Coelhos , Intervenção Coronária Percutânea/efeitos adversos , Tomografia de Coerência Óptica/métodos , Angiografia Coronária , Reestenose Coronária/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Vasos Coronários/patologia , Stents , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Neointima/patologia , Resultado do TratamentoRESUMO
Development of in silico models that capture progression of diseases in soft biological tissues are intrinsic in the validation of the hypothesized cellular and molecular mechanisms involved in the respective pathologies. In addition, they also aid in patient-specific adaptation of interventional procedures. In this regard, a fully-coupled high-fidelity Lagrangian finite element framework is proposed within this work which replicates the pathology of in-stent restenosis observed post stent implantation in a coronary artery. Advection-reaction-diffusion equations are set up to track the concentrations of the platelet-derived growth factor, the transforming growth factor-ß, the extracellular matrix, and the density of the smooth muscle cells. A continuum mechanical description of volumetric growth involved in the restenotic process, coupled to the evolution of the previously defined vessel wall constituents, is presented. Further, the finite element implementation of the model is discussed, and the behavior of the computational model is investigated via suitable numerical examples. Qualitative validation of the computational model is presented by emulating a stented artery. Patient-specific data are intended to be integrated into the model to predict the risk of in-stent restenosis, and thereby assist in the tuning of stent implantation parameters to mitigate the risk.
Assuntos
Reestenose Coronária , Stents , Humanos , Reestenose Coronária/patologia , Análise de Elementos Finitos , Simulação por Computador , Vasos Coronários/cirurgiaRESUMO
BACKGROUND: Coronary stenosis can be caused de novo atherosclerosis, in-stent restenosis, and in-stent neoatherosclerosis, three entities that develop from a diverse pathophysiological milieu. OBJECTIVE: This study aims to investigate, using optical coherence tomography (OCT), whether or not coronary lesions related to these processes differ in their local inflammatory profile. METHODS: Retrospective analysis of patients with diagnosed or suspected coronary lesions who had undergone OCT imaging for clinical reasons. Macrophage and intra-plaque neovascularization were assessed by OCT and used as surrogates of local inflammation. A significance level of < 0.05 was adopted as statistically significant. RESULTS: From the 121 lesions, 74 were de novo, 29 were restenosis, and 18 were neoatherosclerosis. Neovascularization was found in 65.8% of de novo, 10.3% in restenosis, and 94.4% in neoatherosclerosis (p<0.01 for all). The volume of neovascularization was different among lesion types (950 vs. 0 vs. 6220, respectively [median values in 1000 x µm3/mm]; p<0.01 for all), which were significantly higher in neoatherosclerosis and lower in restenosis. The presence of macrophages differed among the lesions (95.9% in de novo vs. 6.9% in restenosis vs. 100% in neoatherosclerosis [p<0.01 for all]). Moreover, the intensity of macrophagic infiltration was different among lesion types (2.5 vs. 0.0 vs. 4.5, respectively [median values of macrophage score]; p<0.01 for all), significantly higher in neoatheroscleosis and lower in restenosis. CONCLUSION: When compared using coronary OCT, de novo atherosclerosis, in-stent restenosis, and neoatherosclerosis presented markedly different inflammatory phenotypes.
FUNDAMENTO: A estenose coronária pode ser causada por de novo aterosclerose, reestenose intra-stent e neoaterosclerose intra-stent, três entidades que se desenvolvem a partir de diversos meios fisiopatológicos. OBJETIVOS: Este estudo tem como objetivo investigar, por meio da tomografia de coerência óptica (OCT), se as lesões coronarianas relacionadas a esses processos diferem em seu perfil inflamatório local. MÉTODOS: Análise retrospectiva de pacientes com lesões coronárias diagnosticadas ou suspeitas que realizaram exames de OCT por motivos clínicos. Macrófagos e neovascularização intraplaca foram avaliados por OCT e utilizados como marcadores de inflamação local. O nível de significância < 0,05 foi adotado como estatisticamente significante. RESULTADOS: Das 121 lesões, 74 eram de novo , 29 eram reestenose e 18 eram neoaterosclerose. Neovascularização foi encontrada em 65,8% das de novo , 10,3% na reestenose e 94,4% na neoaterosclerose (p<0,01 para todos). O volume de neovascularização foi diferente entre os tipos de lesão (950 vs. 0 vs. 6.220, respectivamente [valores medianos em 1000 x µm 3 /mm]; p<0,01 para todos), sendo significativamente maior na neoaterosclerose e menor na reestenose. A presença de macrófagos diferiu entre as lesões (95,9% em de novo vs. 6,9% em reestenose vs. 100% em neoaterosclerose [p<0,01 para todos]). Além disso, a intensidade da infiltração macrofágica foi diferente entre os tipos de lesão (2,5 vs. 0,0 vs. 4,5, respectivamente [valores medianos do escore de macrófagos]; p<0,01 para todos), significativamente maior na neoaterosclerose e menor na reestenose. CONCLUSÕES: Quando comparados pela OCT coronariana, de novo , reestenose intra-stent e neoaterosclerose apresentaram fenótipos inflamatórios marcadamente diferentes.
Assuntos
Aterosclerose , Reestenose Coronária , Stents Farmacológicos , Doenças das Valvas Cardíacas , Intervenção Coronária Percutânea , Humanos , Tomografia de Coerência Óptica/efeitos adversos , Tomografia de Coerência Óptica/métodos , Neointima/diagnóstico por imagem , Neointima/complicações , Neointima/patologia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Aterosclerose/complicações , Stents/efeitos adversos , Doenças das Valvas Cardíacas/patologia , Constrição Patológica , Intervenção Coronária Percutânea/efeitos adversos , FenótipoRESUMO
BACKGROUND: Calcified nodules (CN) have been reported as being associated with stent failure including in-stent restenosis (ISR). However, there is no systematic study of this condition. AIMS: We aimed to clarify the prevalence, predictors, and midterm results of ISR lesions with CN. METHODS: We examined the clinical characteristics of 651 ISR lesions in patients who underwent percutaneous coronary intervention (PCI) with optical coherence tomography (OCT) between October 2008 and July 2016, and their 6- to 8-month follow-up angiography results. CN was defined as a high backscattering mass with small nodular calcium depositions which protruded into the vessel lumen. RESULTS: Thirty-two ISR lesions (4.9%) had CN. Multivariable analysis showed that calcified lesion (odds ratio [OR] 12.441, p<0.001), incomplete stent apposition (OR 3.228, p=0.005), haemodialysis (OR 3.633, p=0.024), and female gender (OR 3.212, p=0.036) were independently associated with ISR lesions with CN. Midterm follow-up was performed on 612 ISR lesions. Both ISR and target lesion revascularisation (TLR) rates were significantly higher in lesions with CN compared with those without CN (43.8% vs 25.0%, p=0.023; 37.5% vs 18.8%, p=0.020, respectively). However, multivariate analysis did not show the presence of CN as an independent predictor of re-TLR (OR 1.690, p=0.286). CONCLUSIONS: The prevalence of ISR lesions with CN was 4.9%. Calcified lesions, incomplete stent apposition, haemodialysis, and female gender are probably associated with CN formation. ISR lesions with CN may have poor midterm outcomes compared with ISR lesions without CN.
Assuntos
Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Angiografia Coronária/métodos , Reestenose Coronária/epidemiologia , Reestenose Coronária/patologia , Reestenose Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Prevalência , Fatores de Risco , Stents/efeitos adversos , Resultado do TratamentoRESUMO
Platelets in atherosclerosis, bypass stenosis, and restenosis have been extensively assessed. However, a sequential ultrastructural study of platelets in angiogenesis during the early phases of these lesions has received less attention. Our objective was the study of platelets in angiogenesis and vessel regression during intimal thickening (IT) formation, a precursor process of these occlusive vascular diseases. For this purpose, we used an experimental model of rat occluded arteries and procedures for ultrastructural observation. The results show (a) the absence of platelet adhesion in the de-endothelialized occluded arterial segment isolated from the circulation, (b) that intraarterial myriad platelets contributed from neovessels originated by sprouting angiogenesis from the periarterial microvasculature, (c) the association of platelets with blood components (fibrin, neutrophils, macrophages, and eosinophils) and non-polarized endothelial cells (ECs) forming aggregates (spheroids) in the arterial lumen, (d) the establishment of peg-and-socket junctions between platelets and polarized Ecs during intussusceptive angiogenesis originated from the EC aggregates, with the initial formation of IT, and (e) the aggregation of platelets in regressing neovessels ('transitory paracrine organoid') and IT increases. In conclusion, in sprouting and intussusceptive angiogenesis and vessel regression during IT formation, we contribute sequential ultrastructural findings on platelet behavior and relationships, which can be the basis for further studies using other procedures.
Assuntos
Artérias/patologia , Plaquetas/metabolismo , Neovascularização Patológica/patologia , Adesividade Plaquetária/fisiologia , Túnica Íntima/patologia , Animais , Artérias/ultraestrutura , Aterosclerose/patologia , Reestenose Coronária/patologia , Ratos , Ratos Sprague-Dawley , Túnica Íntima/ultraestrutura , Remodelação Vascular/fisiologiaRESUMO
BACKGROUND: In-stent restenosis usually occurs by platelet activation, neointima formation, VSMC migration, and proliferation in the position of the vessel stent. The monocytes have a magnificent role in neointimal hyperplasia since these cells recruit to the site of vessel injury through chemokines and other secretion proteins. This study is focused on the investigation of vitronectin, miR-193, miR-34, and miR-520 expression levels in PBMCs isolated from stenosed patients. METHODS: A total of sixty subjects undergoing coronary artery angiography containing patients with stent no restenosis (n = 20), in-stent restenosis (n = 20), and healthy participants (n = 20) participated in the study. The vitronectin, miR-193, miR-34, and miR-520 expression levels were measured by the RT-qPCR technique. Data were analyzed by SPSS software. RESULTS: The vitronectin, miR-34, and miR-520 expression levels changed significantly in patients with vessel in-stent restenosis (p = 0.02, p = 0.02, and p = 0.01, respectively). Furthermore, there were inverse correlations between the expression levels of vitronectin gene and miR-34 (r = - 0.44, p = 0.04) as well as miR-520 (r = - 0.5, p=0.01). CONCLUSIONS: The molecular events in the vessel stenosis may be affected by targeting vitronectin with miR-520 and miR-34.
Assuntos
Estenose Coronária/genética , MicroRNAs/genética , Vitronectina/metabolismo , Idoso , Movimento Celular/fisiologia , Constrição Patológica/patologia , Angiografia Coronária/métodos , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Estenose Coronária/metabolismo , Vasos Coronários/metabolismo , Feminino , Expressão Gênica/genética , Humanos , Hiperplasia/patologia , Irã (Geográfico) , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Neointima/patologia , Transdução de Sinais/fisiologia , Stents/efeitos adversos , Transcriptoma/genética , Vitronectina/genéticaRESUMO
BACKGROUND: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION®) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine®) in a porcine coronary restenosis model. METHODS: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1-1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. RESULTS: Quantitative coronary analysis showed no significant differences in the pre-procedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). CONCLUSION: Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.
Assuntos
Reestenose Coronária/tratamento farmacológico , Stents Farmacológicos , Everolimo/uso terapêutico , Animais , Angiografia Coronária , Reestenose Coronária/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Everolimo/química , Polímeros/química , Suínos , Porco Miniatura , Titânio/química , Tomografia de Coerência ÓpticaRESUMO
ABSTRACT: Percutaneous coronary intervention has become the main revascularization strategy for coronary artery disease. Compared with early percutaneous coronary angioplasty and the extensive clinical application of bare metal stents, drug-eluting stents can significantly reduce the stenosis caused by the elastic retraction of plaque and neoatherosclerosis (NA), but there is still a high incidence of in-stent restenosis (ISR), which restricts the clinical efficacy of stent implantation. In-stent neoatherosclerosis (ISNA), defined as atherosclerotic lesions in the neointima, is one of the main causes of late stent failure. ISNA plays an important role in stent thrombosis and ISR. The rate of target lesion revascularization and in-stent thrombosis is high when NA arises. Therefore, it is of great clinical significance to explore the occurrence of NA and its development mechanism after stent implantation to prevent ISR and improve stent implantation efficacy and associated clinical prognosis. In this article, we systematically reviewed the existing clinical research on ISNA and the role of optical coherence tomography in its evaluation.
Assuntos
Doença da Artéria Coronariana/terapia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Vasos Coronários/patologia , Neointima , Intervenção Coronária Percutânea/instrumentação , Placa Aterosclerótica , Stents , Animais , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/patologia , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/patologia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Fatores de Risco , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
Diabetes is a major risk factor for the development of cardiovascular disease. Diabetic patients have a higher incidence of restenosis following endovascular therapy than non-diabetic patients. Melatonin is primarily synthesized and secreted by the pineal gland and plays an important protective anti-inflammatory and antioxidant role in a variety of cardiovascular diseases. However, no studies to date have evaluated the underlying effects and molecular mechanisms of melatonin on diabetes-related restenosis. Herein, we used an in vivo model of diabetes-related restenosis and an in vitro model of high glucose-cultured vascular smooth muscle cells to investigate the anti-restenosis effect and signaling mechanisms induced by melatonin treatment. The present study provides the first evidence that melatonin attenuates restenosis following vascular injury in diabetic rats. We further investigated the underlying molecular mechanisms both in vivo and in vitro. The data suggest that the Nrf2 signaling pathway is an important molecular target for melatonin-mediated inhibition of diabetes-related restenosis after vascular injury. These findings indicate that melatonin may represent a potential candidate for the prevention or treatment of vascular diseases and restenosis following endovascular therapy, especially in diabetic patients.
Assuntos
Reestenose Coronária/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Melatonina/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Lesões do Sistema Vascular/tratamento farmacológico , Animais , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Reestenose Coronária/complicações , Reestenose Coronária/patologia , Citoproteção/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Glucose/toxicidade , Heme Oxigenase-1/metabolismo , Hiperplasia , Masculino , Melatonina/farmacologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lesões do Sistema Vascular/complicações , Lesões do Sistema Vascular/patologiaRESUMO
While the advent of drug-eluting stents has been clinically effective in substantially reducing the rates of major stent-related adverse events compared with bare metal stents, vascular biological problems such as neointimal hyperplasia, delayed re-endothelialization, late stent thrombosis are not eliminated and, increasingly, neoatherosclerosis is the underlying mechanism for very late stent failure. Further understanding regarding the mechanisms underlying the biological responses to stent deployment is therefore required so that new and improved therapies can be developed. This review will discuss the accumulating evidence that the chemokines, small inflammatory proteins, play a role in each key biological process of stent biocompatibility. It will address the chemokine system in its specialized roles in regulating the multiple facets of vascular biocompatibility including neointimal hyperplasia, endothelial progenitor cell (EPC) mobilization and re-endothelialization after vascular injury, platelet activation and thrombosis, as well as neoatherosclerosis. The evidence in this review suggests that chemokine-targeting strategies may be effective in controlling the pathobiological processes that lead to stent failure. Preclinical studies provide evidence that inhibition of specific chemokines and/or broad-spectrum inhibition of the CC-chemokine class prevents neointimal hyperplasia, reduces thrombosis and suppresses the development of neoatherosclerosis. In contrast, however, to these apparent deleterious effects of chemokines on stent biocompatibility, the CXC chemokine, CXCL12, is essential for the mobilization and recruitment of EPCs that make important contributions to re-endothelialization post-stent deployment. This suggests that future chemokine inhibition strategies would need to be correctly targeted so that all key stent biocompatibility areas could be addressed, without compromising important adaptive biological responses.
Assuntos
Materiais Biocompatíveis , Quimiocinas/metabolismo , Doença da Artéria Coronariana/terapia , Vasos Coronários/metabolismo , Intervenção Coronária Percutânea/instrumentação , Stents , Animais , Quimiocinas/imunologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Reestenose Coronária/imunologia , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Trombose Coronária/imunologia , Trombose Coronária/metabolismo , Trombose Coronária/patologia , Vasos Coronários/imunologia , Vasos Coronários/patologia , Stents Farmacológicos , Humanos , Hiperplasia , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Transdução de Sinais , Resultado do TratamentoRESUMO
Interventional therapies such as drug-eluting stents (DES) and drug-coated balloons (DCB) have significantly improved the clinical outcomes of patients with coronary occlusions in recent years. Despite this marked improvement, ischemic cardiovascular disease remains the most common cause of death worldwide. To address this, research efforts are focused on improving the safety and efficacy of the next generation of these devices. However, current experimental methods are unable to account for the influence of atherosclerotic lesions on drug uptake and retention. Therefore, in this study, we used an integrated approach utilizing both in vitro and in silico methods to assess the performance of DCB therapy. This approach was validated against existing in vivo results before being used to numerically estimate the effect of the atheroma. A bolus release of sirolimus was observed with our coating matrix. This, coupled with the rapid saturation of specific and non-specific binding sites observed in our study, indicated that increasing the therapeutic dose coated onto the balloons might not necessarily result in greater uptake and/or retention. Additionally, our findings alluded to an optimal exposure time, dependent on the coating matrix, for the DCBs to be expanded against the vessel. Moreover, our findings suggest that a biphasic drug release profile might be beneficial for establishing and maintaining the saturation of bindings sites within severely occluded vessels. Ultimately, we have demonstrated that computational methods may be capable of assessing the efficacy of DCB therapy as well as predict the influence of atherosclerotic lesions on said efficacy.