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1.
Int Heart J ; 61(5): 872-878, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921669

RESUMO

In-stent restenosis (ISR) still exists after drug-eluting stent (DES) implantation, even up to one year. The incidence and risk factors for neoatherosclerosis in patients with early ISR have not yet been elucidated. Here, we used optical coherence tomography (OCT) to evaluate the incidence and predictors of neoatherosclerosis in patients with early ISRs.OCT was performed on ISR lesions in 185 patients in order to detect neoatherosclerosis. The median follow-up was 180 days, and neoatherosclerosis was detected in 37% of early ISR lesions. According to the presence of neoatherosclerosis, patients with ISR were divided into two groups: neoatherosclerosis (group A, n = 69) and non-neoatherosclerosis (group B, n = 116) groups.The risk factors were similar, except for hypercholesterolemia. Moreover, the tissue characteristics were not significantly different between patients with and without neoatherosclerosis. Follow-up low-density lipoprotein-cholesterol (LDL-C) levels were divided into three grades (LDL < 70 mg/dL, 70 mg/dL≤ LDL < 100 mg/dL, and LDL ≥ 100 mg/dL). The incidence of neoatherosclerosis was significantly lower (23% versus 57%, P < 0.0001) in the LDL < 70 mg/dL group. There was no significant difference in the incidence of neoatherosclerosis in patients with lipid levels between 70 and 100 mg/dL (P = 0.53). However, neoatherosclerosis was significantly more common in patients with a follow-up LDL-C level > 100 mg/dL (45% versus 15%, P < 0.0001).In patients with early ISR lesions, the LDL-C levels may be related to the formation and progression of early neoatherosclerosis, and poor LDL-C control may be a risk factor for the occurrence of early-stage neoatherosclerosis following DES implantation.


Assuntos
LDL-Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Reestenose Coronária/epidemiologia , Stents Farmacológicos , Hipercolesterolemia/epidemiologia , Neointima/epidemiologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico por imagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Incidência , Masculino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Fatores de Risco , Tomografia de Coerência Óptica
2.
Int Heart J ; 61(5): 1041-1043, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879262

RESUMO

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Doença de Hodgkin/radioterapia , Lesões por Radiação/terapia , Stents , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediastino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Tomografia de Coerência Óptica
4.
J Vis Exp ; (161)2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32716387

RESUMO

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the luminal surface area in arteries thereby reducing adequate blood flow to organs and distal tissues. Clinically, revascularization procedures such as balloon angioplasty with or without stent placement aim to restore blood flow. Although these procedures reestablish blood flow by reducing plaque burden, they damage the vessel wall, which initiates the arterial healing response. The prolonged healing response causes arterial restenosis, or re-narrowing, ultimately limiting the long-term success of these revascularization procedures. Therefore, preclinical animal models are integral for analyzing the pathophysiological mechanisms driving restenosis, and provide the opportunity to test novel therapeutic strategies. Murine models are cheaper and easier to operate on than large animal models. Balloon or wire injury are the two commonly accepted injury modalities used in murine models. Balloon injury models in particular mimic the clinical angioplasty procedure and cause adequate damage to the artery for the development of restenosis. Herein we describe the surgical details for performing and histologically analyzing the modified, pressure-controlled rat carotid artery balloon injury model. Additionally, this protocol highlights how local periadventitial application of therapeutics can be used to inhibit neointimal hyperplasia. Lastly, we present light sheet fluorescence microscopy as a novel approach for imaging and visualizing the arterial injury in three-dimensions.


Assuntos
Angioplastia com Balão/efeitos adversos , Lesões das Artérias Carótidas/patologia , Animais , Aterosclerose/patologia , Artérias Carótidas/patologia , Humanos , Camundongos , Neointima/patologia , Ratos
5.
Int Heart J ; 61(4): 665-672, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684594

RESUMO

Clinical outcomes after percutaneous coronary intervention (PCI) for severely calcified lesions remain poor. The purpose of this study was to investigate the neointimal response after everolimus-eluting stents (EES) for severely calcified lesions treated with rotational atherectomy (RA) using optical coherence tomography (OCT).We retrospectively analyzed 34 lesions in which PCI was performed with EES deployment following RA and OCT was performed immediately after PCI and at follow-up (nine months). The EES was either durable-polymer (DP) EES (22 lesions) or bioabsorbable polymer (BP) -EES (12 lesions). Strut coverage and malapposition were evaluated at 1-mm intervals of cross-section (CS) by serial OCT analysis. Malapposed strut was defined as having the distance from luminal border > 100 µm.A total of 11,823 struts immediately after PCI and 11,720 struts at follow-up were analyzed. Immediately after PCI, the strut-level analysis showed no significant differences in the percentage of malapposed struts between the DP-EES group and the BP-EES group. At follow-up, the BP-EES group showed a more prevalent covered strut compared with the DP-EES group (strut-level analysis: 95% versus 97%, P = 0.045; CS-level analysis: 97% versus 100%, P < 0.01; lesion-level analysis: 27% versus 83%, P < 0.01, respectively).In severely calcified lesions requiring RA, the BP-EES group achieved better neointimal coverage than the DP-EES group at nine months. Additional prospective studies are needed.


Assuntos
Implantes Absorvíveis/estatística & dados numéricos , Aterectomia Coronária/instrumentação , Stents Farmacológicos/estatística & dados numéricos , Neointima/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Everolimo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polímeros , Estudos Retrospectivos , Tomografia de Coerência Óptica
6.
Arterioscler Thromb Vasc Biol ; 40(8): 1870-1890, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32493169

RESUMO

OBJECTIVE: Neointima formation is a primary cause of intermediate to late vein graft (VG) failure. However, the precise source of neointima cells in VGs remains unclear. Approach and Results: Herein we clarify the relative contributions of mature vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to neointima formation in a mouse model of VG remodeling via the genetic-inducible fate mapping approaches. Regardless of the magnitude of neointima formation, the recipient arterial and the donor venous SMCs contributed ≈55% of the neointima cells at the anastomotic regions, whereas only donor venous SMCs donated ≈68% of the neointima cells at the middle bodies. A small portion of the SMC-derived cells became non-SMC cells, most likely vascular stem cells, and constituted 2% to 11% of the cells in each major layer of VGs. In addition, the recipient arterial ECs were the major cellular source of re-endothelialization but did not contribute to neointima formation. The donor venous ECs donated ≈17% neointima cells in the VGs with mild neointima formation and conditional media from ECs after endothelial-to-mesenchymal transition suppressed vascular SMC dedifferentiation. CONCLUSIONS: The recipient arterial and donor venous mature SMCs dominate but contribute distinctly to intimal hyperplasia at the anastomosis and the middle body regions of VGs. The recipient arterial ECs are the major cellular source of re-endothelialization but do not donate neointima formation in VGs. Only the donor venous ECs undergo endothelial-to-mesenchymal transition. Endothelial-to-mesenchymal transition is marginal for generating neointima cells but is likely required for controlling the quality of VG remodeling.


Assuntos
Células Endoteliais/patologia , Veias Jugulares/transplante , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Neointima/patologia , Animais , Hiperplasia , Mesoderma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Remodelação Vascular
7.
Arterioscler Thromb Vasc Biol ; 40(7): e214-e226, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32493171

RESUMO

OBJECTIVE: Mitochondria consistently change their morphology in a process regulated by proteins, including Drp1 (dynamin-related protein 1), a protein promoting mitochondrial fission. Drp1 is involved in the mechanisms underlying various cardiovascular diseases, such as myocardial ischemia/reperfusion injury, heart failure, and pulmonary arterial hypertension. However, its role in macrophages, which promote various vascular diseases, is poorly understood. We therefore tested our hypothesis that macrophage Drp1 promotes vascular remodeling after injury. METHOD AND RESULTS: To explore the selective role of macrophage Drp1, we created macrophage-selective Drp1-deficient mice and performed femoral arterial wire injury. In these mice, intimal thickening and negative remodeling were attenuated at 4 weeks after injury when compared with control mice. Deletion of macrophage Drp1 also attenuated the macrophage accumulation and cell proliferation in the injured arteries. Gain- and loss-of-function experiments using cultured macrophages indicated that Drp1 induces the expression of molecules associated with inflammatory macrophages. Morphologically, mitochondrial fission was induced in inflammatory macrophages, whereas mitochondrial fusion was induced in less inflammatory/reparative macrophages. Pharmacological inhibition or knockdown of Drp1 decreased the mitochondrial reactive oxygen species and chemotactic activity in cultured macrophages. Co-culture experiments of macrophages with vascular smooth muscle cells indicated that deletion of macrophage Drp1 suppresses growth and migration of vascular smooth muscle cells induced by macrophage-derived soluble factors. CONCLUSIONS: Macrophage Drp1 accelerates intimal thickening after vascular injury by promoting macrophage-mediated inflammation. Macrophage Drp1 may be a potential therapeutic target of vascular diseases.


Assuntos
Dinaminas/metabolismo , Artéria Femoral/metabolismo , Macrófagos Peritoneais/metabolismo , Mitocôndrias/metabolismo , Neointima , Remodelação Vascular , Lesões do Sistema Vascular/metabolismo , Animais , Proliferação de Células , Quimiotaxia , Técnicas de Cocultura , Modelos Animais de Doenças , Dinaminas/deficiência , Dinaminas/genética , Artéria Femoral/lesões , Artéria Femoral/patologia , Artéria Femoral/fisiopatologia , Ativação de Macrófagos , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/patologia , Dinâmica Mitocondrial , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fatores de Tempo , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologia , Lesões do Sistema Vascular/fisiopatologia
8.
Cardiovasc Pathol ; 49: 107230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32585603

RESUMO

PURPOSE: Restenosis is the main complication after percutaneous coronary intervention. The proliferation of new intima contributes to the process. In this study, we aimed to explore the effect of olmesartan on intimal thickening after balloon injury and possible mechanism. METHODS: Aortic endothelial denudation model was made by a 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Control (n = 12) Surgery (n = 12, received vascular balloon injury) and Olmesartan (n = 12, received 3 mg.kg-1.d-1olmesartan after injury). Fourteen and 28 days after injury, HE staining was used to assess the aortic endothelial injury. Radioimmunological method was used to examine the level of angiotensin II (Ang II). Western blotting and reverse transcription polymerse chain reaction (RT-PCR) were employed to detect the protein and mRNA level of Apelin/APJ. RESULTS: After vascular balloon injury, the proliferation of vascular smooth muscle cells and the intimal thickening were increased. The mRNA and protein level of Ang II, AT1, Apelin and APJ mRNA were promoted by vascular balloon injury. Olmesartan decreased the proliferation of vascular smooth muscle cells and the intimal thickening. Olmesartan decreased the expression of Ang II and AT1, but further increased the expression of Apelin and APJ. Balloon injury also induced the activation of Extracellular signal-regulated kinase (ERK) signaling and olmesartan decreased the effect. CONCLUSION: Olmesartan inhibits the intimal thickening through activating Apelin/APJ and inhibiting AngII-AT1 and ERK pathway.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Receptores de Apelina/metabolismo , Apelina/metabolismo , Imidazóis/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima , Tetrazóis/farmacologia , Lesões do Sistema Vascular/tratamento farmacológico , Angioplastia com Balão , Angiotensina II/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/lesões , Aorta/metabolismo , Aorta/patologia , Proliferação de Células/efeitos dos fármacos , Constrição Patológica , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Músculo Liso Vascular/lesões , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fosforilação , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia
9.
J Cardiovasc Pharmacol Ther ; 25(6): 570-577, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32515207

RESUMO

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.


Assuntos
Angioplastia com Balão/instrumentação , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/terapia , Lesões das Artérias Carótidas/prevenção & controle , Estenose das Carótidas/prevenção & controle , Clopidogrel/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Stents , Ticagrelor/farmacologia , Angioplastia com Balão/efeitos adversos , Animais , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/patologia , Estenose das Carótidas/etiologia , Estenose das Carótidas/patologia , Modelos Animais de Doenças , Hiperplasia , Masculino , Neointima , Coelhos
10.
J Surg Res ; 253: 280-287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402853

RESUMO

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.


Assuntos
Artérias Carótidas/cirurgia , Neointima/prevenção & controle , Fotoquimioterapia/métodos , Veia Safena/transplante , Enxerto Vascular/métodos , Túnica Adventícia/efeitos dos fármacos , Túnica Adventícia/efeitos da radiação , Animais , Colágeno/química , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Feminino , Corantes Fluorescentes/administração & dosagem , Luz , Neointima/diagnóstico , Neointima/etiologia , Neointima/patologia , Rosa Bengala/administração & dosagem , Veia Safena/diagnóstico por imagem , Veia Safena/patologia , Suínos , Porco Miniatura , Transplante Autólogo/efeitos adversos , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Enxerto Vascular/efeitos adversos , Grau de Desobstrução Vascular
11.
Ann Vasc Surg ; 68: 468-475, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32422286

RESUMO

BACKGROUND: The spiral saphenous vein graft is an excellent choice for venous reconstruction after periphery vein injury, but only few cases have been reported. We implanted a segment of a single saphenous vein into both the popliteal vein as a venous vein graft and into the popliteal artery as an arterial vein graft at the same time in a trauma patient; we then had an extraordinary opportunity to harvest and examine both patent venous and arterial vein grafts at 2 weeks after implantation. METHODS: A spiral saphenous vein graft was made as previously described and implanted into the popliteal vein and artery as interposition grafts; because of the patient's serious injuries, an amputation was performed at day 18 after vascular reconstruction. The grafts were harvested, fixed, and examined using histology and immunohistochemistry. RESULTS: Both grafts were patent, and there was a larger neointimal area in the venous graft compared to the arterial graft. There were CD31- and vWF-positive cells on both neointimal endothelia, with subendothelial deposition of α-actin-, CD3-, CD45-, and CD68-positive cells. There were fewer cells in the venous graft neointima compared to the arterial graft neointima; however, there were more inflammatory cells in the neointima of the venous graft. Some of the neointimal cells were PCNA-positive, whereas very few cells were cleaved caspase-3 positive. The venous graft neointimal endothelial cells were Eph-B4 and COUP-TFII positive, while the arterial graft neointimal endothelial cells were dll-4 and Ephrin-B2 positive. CONCLUSIONS: The spiral saphenous vein graft remains a reasonable choice for vessel reconstruction, especially in the presence of diameter mismatch. Both the venous and arterial grafts showed similar re-endothelialization and cellular deposition; the venous graft had more neointimal hyperplasia and inflammation. At an early time, endothelial cells showed venous identity in the venous graft, whereas endothelial cells showed arterial identity in the arterial graft. CLINICAL RELEVANCE: Veins can be used as venous or arterial vein grafts but venous grafts have more neointimal hyperplasia and inflammation; vein grafts acquire different vessel identity depending on the environment into which they are implanted.


Assuntos
Plasticidade Celular , Células Endoteliais/patologia , Traumatismos da Perna/cirurgia , Artéria Poplítea/cirurgia , Veia Poplítea/cirurgia , Veia Safena/transplante , Enxerto Vascular , Lesões do Sistema Vascular/cirurgia , Amputação , Biomarcadores/metabolismo , Microambiente Celular , Células Endoteliais/metabolismo , Humanos , Escala de Gravidade do Ferimento , Traumatismos da Perna/diagnóstico , Traumatismos da Perna/metabolismo , Masculino , Pessoa de Meia-Idade , Neointima , Artéria Poplítea/lesões , Artéria Poplítea/metabolismo , Artéria Poplítea/patologia , Veia Poplítea/lesões , Veia Poplítea/metabolismo , Veia Poplítea/patologia , Veia Safena/metabolismo , Veia Safena/patologia , Resultado do Tratamento , Grau de Desobstrução Vascular , Remodelação Vascular , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/metabolismo
12.
J Surg Res ; 254: 165-169, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32445932

RESUMO

BACKGROUND: Vein graft stenosis is a major complication of coronary artery bypass surgery and peripheral arterial bypass procedures. Experimental models of this clinical complication have used in vivo grafting procedures, relying on the relatively modest neointimal thickening in these models as a surrogate for clinical graft stenosis without regard to the donor site origin of the vein graft. MATERIALS AND METHODS: In a standard rat model of vein grafting, three different donor sites were used to supply veins used as interpositional grafts to the femoral artery: the superficial inferior epigastric vein, the common femoral vein, and the posterior facial vein (distal branch of the jugular vein). Grafts were harvested as 4 wk and histomorphometrically evaluated for the extent of neointimal formation and lumen narrowing. RESULTS: The posterior facial vein showed significantly thicker neointima and a greater extent of lumen narrowing than the other two graft sources, despite having a similar diameter to the femoral vein and nearly twice the initial diameter of the epigastric vein. CONCLUSIONS: The source of donor graft material can greatly influence the extent of neointimal response after interpositional vein grafting to arterial flow. These findings support use of the posterior facial vein graft over other more standard donor vein grafts in research directed at understanding the causes and prevention of vein graft stenosis.


Assuntos
Neointima/etiologia , Enxerto Vascular , Veias/transplante , Animais , Feminino , Ratos Endogâmicos Lew
13.
J Vasc Res ; 57(4): 223-235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396897

RESUMO

BACKGROUND: There are very few animal models of balloon angioplasty injury in arteriovenous fistula (AVF), hindering insight into the pathophysiologic processes following angioplasty in AVF. The objective of the study was to develop and characterize a rat model of AVF angioplasty injury. METHODS: Balloon angioplasty in 12- to 16-week-old Sprague-Dawley rats was performed at the arteriovenous anastomosis 14 days post-AVF creation with a 2F Fogarty balloon catheter. Morphometry and protein expression of endothelial nitric oxide synthase (eNOS), monocyte-chemoattractant protein-1 (MCP-1), alpha-smooth muscle actin (α-SMA), CD68 (macrophage marker), and collagen expression in AVFs with and without angioplasty were assessed. RESULTS: In AVFs with angioplasty versus without angioplasty: (1) angioplasty increased AVF-vein and artery intimal hyperplasia, (2) angioplasty decreased eNOS protein expression in AVF-vein and artery at 21 days post-AVF creation and remained decreased in the AVF-vein angioplasty group at 35 days, (3) angioplasty increased AVF-vein and artery α-SMA expression within the intimal region at 35 days, (4) angioplasty increased the expression of AVF-vein MCP-1 at 21 days and CD68 at 21 and 35 days, and (5) angioplasty increased AVF-vein and artery collagen expression at 35 days. CONCLUSION: Our findings describe a reproducible rat model to better understand the pathophysiologic mechanisms that ensue following AVF angioplasty.


Assuntos
Angioplastia com Balão , Derivação Arteriovenosa Cirúrgica , Artéria Femoral/lesões , Veia Femoral/lesões , Remodelação Vascular , Lesões do Sistema Vascular/etiologia , Actinas/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Quimiocina CCL2/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Veia Femoral/metabolismo , Veia Femoral/patologia , Veia Femoral/cirurgia , Masculino , Neointima , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia
14.
J Interv Cardiol ; 2020: 1956015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410915

RESUMO

Objectives: We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model. Background: Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited. Methods: Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed. Results: On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™. Conclusions: These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent.


Assuntos
Vasos Coronários , Stents Farmacológicos , Inflamação/prevenção & controle , Neointima/imunologia , Stents/efeitos adversos , Enxerto Vascular/instrumentação , Implantes Absorvíveis , Animais , Materiais Revestidos Biocompatíveis/farmacologia , Vasos Coronários/imunologia , Vasos Coronários/cirurgia , Portadores de Fármacos/farmacologia , Everolimo/farmacologia , Inflamação/etiologia , Modelos Anatômicos , Polímeros/farmacologia , Suínos
15.
Int J Cardiovasc Imaging ; 36(9): 1617-1626, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32462449

RESUMO

Chronic second-generation drug-eluting stent recoil in severely calcified coronary lesions has not been studied. We aimed to evaluate chronic stent recoil by optical coherence tomography (OCT) in severely calcified lesions treated with thin strut stents after rotational atherectomy. In 28 lesions (26 patients with 23% on hemodialysis) treated with everolimus-eluting stents after rotational atherectomy, baseline and 8-month follow-up OCT were compared. Stent recoil was defined as >10% decrease in stent area from baseline to follow-up. Overall, there was no change in minimal stent area (6.0 mm2 [5.0, 8.1] to 6.0 mm2 [4.8, 8.6], p = 0.51) from baseline to follow-up, although neointimal hyperplasia measured 16.3 ± 15.8%. Thirty-six percent of lesions showed stent recoil associated with 6 non-nodular calcifications, 1 calcified nodule, and 3 stent deformations. The overall mean calcium angle with attenuation decreased (54° [29-76] to 31° [19-48], p < 0.0001), and calcium without attenuation increased (28° [21-67] to 64° [34-93], p < 0.0001), but primarily at the location of stent recoil. Furthermore, in the stent recoil segments in 10 recoil lesions, the stent circumference decreased primarily at non-calcium segments rather than at calcium with or without attenuation. One lesion with stent recoil and 2 lesions without stent recoil required repeat revascularization. Thin strut stents can chronically recoil in severely calcified lesions, but this rarely causes restenosis.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Everolimo/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Tomografia de Coerência Óptica , Calcificação Vascular/terapia , Idoso , Aterectomia Coronária , Fármacos Cardiovasculares/efeitos adversos , Doença Crônica , Doença da Artéria Coronariana/diagnóstico por imagem , Everolimo/efeitos adversos , Feminino , Humanos , Masculino , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Desenho de Prótese , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem
16.
Vascular ; 28(4): 396-404, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32228224

RESUMO

BACKGROUND AND OBJECTIVES: Wall shear stress plays a critical role in neointimal hyperplasia after stent implantation. It has been found that there is an inverse relation between wall shear stress and neointimal hyperplasia. This study hypothesized that the increase of arterial wall shear stress caused by arteriovenous fistula could reduce neointimal hyperplasia after stents implantation. METHODS AND RESULTS: Thirty-six male rabbits were randomly divided into three groups: STENT, rabbits received stent implantation into right common carotid artery; STENT/arteriovenous fistula, rabbits received stent implantation into right common carotid artery and carotid-jugular arteriovenous fistula; Control, rabbits received no treatment. After 21 days, stented common carotid artery specimens were harvested for histological staining and protein expression analysis. In STENT group, wall shear stress maintained at a low level from 43.2 to 48.9% of baseline. In STENT/arteriovenous fistula group, wall shear stress gradually increased to 86% over baseline. There was a more significant neointimal hyperplasia in group STENT compared with the STENT/arteriovenous fistula group (neointima area: 0.87 mm2 versus 0.19 mm2; neointima-to-media area ratio: 1.13 versus 0.18). Western blot analysis demonstrated that the protein level of endothelial nitric oxide synthase in STENT group was significantly lower than that in STENT/arteriovenous fistula group, but the protein levels of proliferating cell nuclear antigen, vascular cell adhesion molecule 1, phospho-p38 mitogen-activated protein kinase (Pp38), and phospho-c-Jun N-terminal kinase in STENT group were significantly higher than that in the STENT group. CONCLUSION: High wall shear stress caused by arteriovenous fistula as associated with the induction in neointimal hyperplasia after stent implantation. The underlying mechanisms may be related to modulating the expression and activation of endothelial nitric oxide synthase, vascular cell adhesion molecule 1, p38, and c-Jun N-terminal kinase.


Assuntos
Derivação Arteriovenosa Cirúrgica , Artéria Carótida Primitiva/cirurgia , Procedimentos Endovasculares/instrumentação , Veias Jugulares/cirurgia , Neointima , Animais , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Artéria Carótida Primitiva/fisiopatologia , Procedimentos Endovasculares/efeitos adversos , Hiperplasia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Veias Jugulares/fisiopatologia , Masculino , Modelos Animais , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Antígeno Nuclear de Célula em Proliferação/metabolismo , Coelhos , Fluxo Sanguíneo Regional , Stents , Estresse Mecânico , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
J Surg Res ; 253: 53-62, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32320897

RESUMO

BACKGROUND: Proteoglycan 4 (PRG4; lubricin) is a member of two gene co-expression network modules associated with human vein graft failure. However, little is known about PRG4 and the vascular system. Therefore, we have investigated the effects of recombinant human PRG4 (rhPRG4) on cell migration and proliferation in human veins. METHODS: Effects of rhPRG4 on cell migration, proliferation, and neointima formation were determined in human venous tissue and cultured venous smooth muscle cells (SMCs), adventitial cells, and endothelial cells. Expression of PRG4 by cultured human saphenous veins, failed vein grafts, and varicose veins was determined by immunostaining or Western blotting. RESULTS: Limited expression of PRG4 in fresh saphenous veins was dramatically increased around medial SMCs after culture ex vivo. rhPRG4 inhibited the migration of cultured SMCs, adventitial cells, and endothelial cells, as well as the proliferation of endothelial cells. rhPRG4 also inhibited the migration of SMCs and adventitial cells from tissue explants, but there was no effect on cell proliferation or neointima formation in ex vivo whole veins. Finally, PRG4 was largely absent in two examples of venous pathology, that is, failed human vein grafts and varicose veins. CONCLUSIONS: Although rhPRG4 can inhibit the migration of venous SMCs, endothelial cells, and adventitial cells, and the proliferation of endothelial cells, PRG4 was only increased around medial SMCs in veins after ex vivo culture. PRG4 was not observed around medial SMCs in failed human vein grafts and varicose veins, suggesting the possibility that a failure of PRG4 upregulation may promote these pathologies.


Assuntos
Rejeição de Enxerto/patologia , Neointima/patologia , Proteoglicanas/metabolismo , Veia Safena/transplante , Varizes/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais/patologia , Rejeição de Enxerto/etiologia , Humanos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/patologia , Neointima/etiologia , Técnicas de Cultura de Órgãos , Doença Arterial Periférica/cirurgia , Cultura Primária de Células , Proteoglicanas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Veia Safena/citologia , Veia Safena/patologia , Técnicas de Cultura de Tecidos , Enxerto Vascular/efeitos adversos
18.
Expert Rev Cardiovasc Ther ; 18(5): 261-267, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32321328

RESUMO

INTRODUCTION: Dual antiplatelet therapy (DAPT) is required for coronary artery disease treated with drug-eluting stents (DES) implantation. Shortening DAPT duration would be beneficial for patients with high bleeding risk. AREAS COVERED: Early healing patterns, especially stent strut coverage, assessed by optical coherence tomography (OCT) as a surrogate of neointima have been investigated to make decisions on whether short DAPT would be a safe alternative. This review evaluates the OCT evidence (i.e. neointimal coverage of stent struts within 3 months) for shortening DAPT duration after DES implantation. EXPERT COMMENTARY: Shortening DAPT (i.e. within 3 months) duration after DES implantation might reduce complications including bleeding without increasing stent thrombosis. However, the optimal duration of DAPT after DES implantation is under discussion. Long-term assessment of short DAPT is required for the decision of the new guidelines regarding the recommended duration of DAPT.


Assuntos
Stents Farmacológicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Tomografia de Coerência Óptica/métodos , Doença da Artéria Coronariana/terapia , Hemorragia/induzido quimicamente , Humanos , Neointima , Trombose/etiologia , Resultado do Tratamento
19.
Proc Natl Acad Sci U S A ; 117(18): 9896-9905, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32321834

RESUMO

The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvß1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin ß1/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload and inhibition of neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall. We thus propose a mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Integrina beta1/genética , Trombospondina 1/genética , Fatores de Transcrição/genética , Remodelação Vascular/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Aorta/crescimento & desenvolvimento , Aorta/metabolismo , Artérias Carótidas/crescimento & desenvolvimento , Artérias Carótidas/metabolismo , Microambiente Celular/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Adesões Focais/genética , Humanos , Integrina beta1/metabolismo , Mecanotransdução Celular , Camundongos , Neointima/genética , Neointima/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Trombospondina 1/metabolismo , Fatores de Transcrição/metabolismo , Proteínas rap de Ligação ao GTP/genética
20.
PLoS One ; 15(4): e0227582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302306

RESUMO

Molecular hydrogen is thought to have an inhibitory effect on oxidative stress, thereby attenuating the onset and progression of various diseases including cardiovascular disease; however, few reports have assessed the preventive effect of constitutive inhalation of hydrogen gas on of vascular remodeling. Here, we investigated the effect of constitutive inhalation of hydrogen gas on vascular neointima formation using a cuff-induced vascular injury mouse model. After constitutive inhalation of compressed hydrogen gas (O2 21%, N2 77.7%, hydrogen 1.3%) or compressed air only (O2 21%, N2 79%) by C57BL/6 mice for 2 weeks from 8 weeks of age in a closed chamber, inflammatory cuff injury was induced by polyethylene cuff placement around the femoral artery under anesthesia, and hydrogen gas administration was continued until sampling of the femoral artery. Neointima formation, accompanied by an increase in cell proliferation, was significantly attenuated in the hydrogen group compared with the control group. NADPH oxidase NOX1 downregulation in response to cuff injury was shown in the hydrogen group, but the expression levels of NADPH oxidase subunits, p40phox and p47phox, did not differ significantly between the hydrogen and control groups. Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (⋅OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reduction of oxidative stress, suggesting that constitutive inhalation of hydrogen gas at a safe concentration in the living environment could be an effective strategy for prevention of vascular diseases such as atherosclerosis.


Assuntos
Hidrogênio/administração & dosagem , Isquemia Miocárdica/prevenção & controle , Neointima/prevenção & controle , Remodelação Vascular/efeitos dos fármacos , Lesões do Sistema Vascular/complicações , Administração por Inalação , Animais , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Gases/administração & dosagem , Gases/química , Humanos , Radical Hidroxila/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/patologia , NADPH Oxidase 1/metabolismo , Neointima/etiologia , Neointima/patologia , Nitrogênio/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/administração & dosagem , Ácido Peroxinitroso/metabolismo
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