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1.
Transplant Proc ; 51(9): 3174-3177, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619345

RESUMO

A 19-year-old Asian woman presented to the emergency department with ventricular fibrillation. Emergent coronary angiography revealed a 99% ostial stenosis of the left main coronary trunk, and percutaneous coronary intervention was performed. Takayasu arteritis was suspected, but fluorodeoxyglucose positron emission tomography scanning showed no active inflammation. Cardiac function was affected by ischemic cardiomyopathy, and an extracorporeal left ventricular assisted device was implanted under INTERMACS profile 1 status. Histopathology of the ascending aortic wall at the outflow anastomosis site showed no significant sign of Takayasu arteritis. The absence of systemic inflammation led to the replacement of the extracorporeal left ventricular assisted device with a Jervik 2000 as a bridge to transplant. An orthotropic heart transplant took place after a 39-month wait. Histopathology of the explanted heart revealed intimal and adventitial thickening with destruction of the elastic lamina localized at the sinus of Valsalva. Our final pathologic diagnosis was localized Takayasu arteritis. To counter the increased risk of stenosis or pseudoaneurysm formation at the vascular anastomosis site, anti-inflammatory therapy was essential in Takayasu arteritis. The post-heart transplant immunosuppression regime was considered stronger than that for Takayasu arteritis, and we therefore administered prednisolone, mycophenolate mofetil, and tacrolimus as standard protocol. There have been no signs of either relapse or rejection of transplantation for over 1 year. Further closed observation is required to clarify the long-term outcome of this rare condition with regard to heart transplantation.


Assuntos
Cardiomiopatias/etiologia , Cardiomiopatias/cirurgia , Transplante de Coração , Seio Aórtico/patologia , Arterite de Takayasu/complicações , Arterite de Takayasu/patologia , Feminino , Coração Auxiliar , Humanos , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/cirurgia , Adulto Jovem
2.
J Vet Sci ; 20(3): e20, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161738

RESUMO

A rare case of an unruptured sinus of Valsalva aneurysm (SVA) in a 2-month-old male Maltese terrier weighing 1.0 kg with a heart murmur is presented. A right SVA and a ventricular septal defect (VSD) were diagnosed by echocardiography and cardiac catheterization. The dog died due to a worsening of his condition. The necropsy revealed the sinus of Valsalva to have a diameter of 7 mm and a VSD hole was on the opposite surface. This report is the first to describe an unruptured SVA in the right coronary cusp of a small dog.


Assuntos
Aneurisma Aórtico/veterinária , Doenças do Cão/patologia , Comunicação Interventricular/veterinária , Seio Aórtico/patologia , Animais , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Cateterismo Cardíaco/veterinária , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Evolução Fatal , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/patologia , Masculino , Seio Aórtico/diagnóstico por imagem
3.
Pediatr Cardiol ; 40(6): 1134-1143, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087143

RESUMO

The effect of pregnancy on aortic root in women with repaired conotruncal anomalies (CTA) has not been clarified. This study examined aortic diameters during and after pregnancy in women with repaired CTA. A retrospective review of consecutive pregnant women with repaired CTA was performed for results of echocardiography from 1 year before pregnancy to 3 years after delivery and compared with findings from healthy pregnant volunteers. Participants comprised 42 subjects and 49 deliveries with repaired CTA (CTA group), and 47 healthy pregnant women (control group). Although no maternal aortic events were encountered, aortic diameters during pregnancy increased by 1.0 ± 2.2 mm (maximum, 7.0 mm) in the CTA group and 0.6 ± 1.3 mm (maximum, 3.4 mm) in the control group (p = 0.13). The CTA subgroup with increase in aortic diameter ≥ 3.5 mm during pregnancy showed no reversion to baseline diameter at follow-up > 6 months after delivery. Significant risk factors for increased aortic diameter and no reversal included pulmonary atresia, history of aortopulmonary shunt, older age at repair, and smaller left ventricular end-diastolic diameter pre-pregnancy. Women with repaired CTA tolerated pregnancy and delivery well. However, the aortic root progressively dilated during pregnancy and 1/4 of them, especially those with longstanding high aortic blood flow before repair, showed an increase of aortic root size of ≥ 3.5 mm during the peripartum period; this dilatation tended not to revert to the pre-pregnancy diameter. Therefore, serial measurement of the aortic root during pregnancy and after delivery is recommended in these women.


Assuntos
Aorta/patologia , Valva Aórtica/patologia , Seio Aórtico/patologia , Adulto , Fatores Etários , Aorta/anormalidades , Aorta/diagnóstico por imagem , Valva Aórtica/anormalidades , Valva Aórtica/diagnóstico por imagem , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Parto Obstétrico/efeitos adversos , Dilatação Patológica/etiologia , Ecocardiografia , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Imagem Tridimensional , Imagem por Ressonância Magnética , Masculino , Gravidez , Atresia Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco , Seio Aórtico/diagnóstico por imagem , Fatores de Tempo
4.
Am J Physiol Endocrinol Metab ; 316(5): E895-E907, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30860874

RESUMO

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert potent glucose-lowering effects without increasing risks for hypoglycemia and weight gain. Preclinical studies have demonstrated direct antiatherogenic effects of GLP-1RAs in normoglycemic animal models; however, the underlying mechanisms in hyperglycemic conditions have not been fully clarified. Here we aimed to elucidate the role of AMP-activated protein kinase (AMPK) in antiatherogenic effects of GLP-1RAs in hyperglycemic mice. Streptozotocin-induced hyperglycemic apolipoprotein E-null mice were treated with vehicle, low-dose liraglutide (17 nmol·kg-1·day-1), or high-dose liraglutide (107 nmol·kg-1·day-1) in experiment 1 and the AMPK inhibitor dorsomorphin, dorsomorphin + low-dose liraglutide, or dorsomorphin + high-dose liraglutide in experiment 2. Four weeks after treatment, aortas were collected to assess atherosclerosis. In experiment 1, metabolic parameters were similar among the groups. Assessment of atherosclerosis revealed that high-dose liraglutide treatments reduced lipid deposition on the aortic surface and plaque volume and intraplaque macrophage accumulation at the aortic sinus. In experiment 2, liraglutide-induced AMPK phosphorylation in the aorta was abolished by dorsomorphin; however, the antiatherogenic effects of high-dose liraglutide were preserved. In cultured human umbilical vein endothelial cells, liraglutide suppressed tumor necrosis factor-induced expression of proatherogenic molecules; these effects were maintained under small interfering RNA-mediated knockdown of AMPKα1 and in the presence of dorsomorphin. Conversely, in human monocytic U937 cells, the anti-inflammatory effects of liraglutide were abolished by dorsomorphin. In conclusion, liraglutide exerted AMPK-independent antiatherogenic effects in hyperlipidemic mice with streptozotocin-induced hyperglycemia, with the possible involvement of AMPK-independent suppression of proatherogenic molecules in vascular endothelial cells.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Placa Aterosclerótica/patologia , Seio Aórtico/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Técnicas de Silenciamento de Genes , Hiperglicemia/metabolismo , Macrófagos , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/metabolismo , Seio Aórtico/metabolismo , Seio Aórtico/patologia
5.
Ann Thorac Surg ; 108(3): e157-e159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30853590

RESUMO

Methotrexate has been reported as an immunosuppressive agent associated with lymphoproliferative disorders. This report describes the case of a cardiac methotrexate-induced lymphoproliferative disorder that could be differentiated from a sinus of Valsalva aneurysm rupture by cardiac magnetic resonance imaging and fluorine-18 (18F)-fluorodeoxyglucose positron emission tomography combined with computed tomography. The definitive diagnosis was made by a tissue biopsy that was concomitantly performed with sinus of Valsalva aneurysm repair. Significant regression was seen in response to methotrexate withdrawal. To the best of our knowledge, this is the first case of a cardiac methotrexate-induced lymphoproliferative disorder.


Assuntos
Aneurisma Cardíaco/cirurgia , Neoplasias Cardíacas/cirurgia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/cirurgia , Metotrexato/efeitos adversos , Seio Aórtico/patologia , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biópsia por Agulha , Procedimentos Cirúrgicos Cardíacos/métodos , Diagnóstico Diferencial , Feminino , Seguimentos , Aneurisma Cardíaco/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Transtornos Linfoproliferativos/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Doenças Raras , Seio Aórtico/cirurgia , Resultado do Tratamento
6.
Heart ; 105(3): 234-243, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30121632

RESUMO

CLINICAL INTRODUCTION: A 35-year-old man with multiple cardiovascular risk factors presented with a recent history of fever and acute heart failure. His initial echocardiogram showed evidence of severe aortic regurgitation due to ongoing infective endocarditis. Preoperative coronary angiography revealed no coronary abnormalities. Urgent aortic valve replacement was performed and a 29 mm St Jude mechanical valve was implanted. While blood and resected valvular tissue cultures were negative for bacteria, a PCR-based analysis revealed the presence of penicillin-sensitive Streptococcus pneumoniae. Echocardiographic follow-up study at day 3 showed excellent mechanical valve function with no persistent signs of endocarditis. Eight days after surgery, our patient presented with severe chest pain. The ECG is shown in figure 1A and coronary angiography was performed for diagnostic confirmation (figure 1B-D and online supplementary video 1).DC1SP110.1136/heartjnl-2018-313577.supp1Supplementary file 1 heartjnl;105/3/234/F1F1F1Figure 1(A) 12-lead ECG. (B, C) Selective angiogram of the left main, left anterior descending artery and circumflex artery. (D) Aortic root angiography. QUESTION: Which of the following is most likely the diagnostic?Occlusion of the left anterior descending coronary arteryDissection of the left anterior descending coronary arteryValsalva aneurysm presenting as an acute coronary syndromeLeft anterior descending coronary artery spasmLeft main coronary aneurysm.


Assuntos
Aneurisma Aórtico , Insuficiência da Valva Aórtica , Dor no Peito , Endocardite Bacteriana , Implante de Prótese de Valva Cardíaca , Infecções Pneumocócicas , Complicações Pós-Operatórias , Seio Aórtico , Adulto , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/cirurgia , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Angiografia Coronária/métodos , Diagnóstico Diferencial , Ecocardiografia/métodos , Eletrocardiografia/métodos , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/fisiopatologia , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/fisiopatologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Reoperação/métodos , Seio Aórtico/diagnóstico por imagem , Seio Aórtico/patologia , Streptococcus pneumoniae/isolamento & purificação , Resultado do Tratamento
8.
Am J Hypertens ; 31(12): 1317-1323, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30099532

RESUMO

BACKGROUND: Aortic root (AR) dimension (ARD) at the Valsalva sinuses has been associated with incident cardiovascular (CV) events in population-based studies, but this effect could be due to the association with increased left ventricular (LV) mass. There is also uncertainty on how to define clear-cut AR dilatation. Thus, we analyzed the Campania Salute Network (CSN) registry to (i) establish criteria for evaluation of ARD, (ii) propose cut-points for AR dilatation, and (iii) determine whether AR dilatation has prognostic value independent of LV hypertrophy (LVH). METHODS: We analyzed hypertensive patients with available follow-up, in sinus rhythm and free of prevalent valvular and CV disease (n = 8,573). AR exceeding the 75th percentile of the AR z-score (Ao-Z) obtained by comparison with the value predicted by age, sex, and height (i.e., Ao-Z > 0.80) was considered dilated. RESULTS: Patients with baseline-dilated ARD by Ao-Z were more likely to be younger, men, and obese and had higher baseline blood pressure (BP; all <0.02) but similar kidney function as those without ARD dilatation. In multivariable Cox regression model, dilated ARD predicted 36% increased rate of CV events, independently of older age, male sex, systolic BP, LVH, and class of antihypertensive medications used during follow-up (95% confidence interval: 1.07-1.71, P = 0.011). CONCLUSIONS: In the context of a population of treated hypertensive patients, ARD defined by z-score of predicted values is an independent predictor of CV events regardless of LVH and other common confounders. CLINICAL TRIALS REGISTRATION: Trial Number NCT02211365.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças da Aorta/epidemiologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Seio Aórtico/patologia , Adulto , Idoso , Doenças da Aorta/patologia , Doenças da Aorta/fisiopatologia , Dilatação Patológica , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(8): 806-822, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29678642

RESUMO

BACKGROUND AND AIMS: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE-/- mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis. METHODS: HSP70 was overexpressed in apoE-/- mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE-/- mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [3H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT). RESULTS: Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE-/- mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE-/- mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE-/- mice. CONCLUSIONS: HSP70 promotes the progression of atherosclerosis in apoE-/- mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Aterosclerose/patologia , Proteínas de Choque Térmico HSP70/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Aterosclerose/etiologia , Linhagem Celular , Colesterol/metabolismo , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo , Humanos , Sistema de Sinalização das MAP Quinases , Macrófagos , Masculino , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Regiões Promotoras Genéticas , Seio Aórtico/metabolismo , Seio Aórtico/patologia , Proteínas Elk-1 do Domínio ets/metabolismo
10.
Pol Arch Intern Med ; 128(5): 287-293, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29549696

RESUMO

INTRODUCTION Aortic root (AoR) dilation is associated with cardiac damage and higher cardiovascular risk. Cardiovascular disease is the most common cause of death in patients after kidney transplantation (KTx ). OBJECTIVES The aim of this study was to assess the prevalence of enlarged AoR diameter in KTx recipients. Patients with bicuspid aortic valve, significant valvular disease, or evidence of connective tissue disorder were excluded. PATIENTS AND METHODS A total of 87 KTx recipients were divided into 2 groups depending on immunosuppressive regimen: 41 patients receiving mammalian target of rapamycin inhibitors (mTORi) and 46 patients treated with calcineurin inhibitors (CNIs). In all patients, echocardiography was performed, laboratory and clinical markers of cardiovascular risk were assessed, and the AoR diameter was calculated. RESULTS There were no differences between groups in age, sex, body surface area, body mass index, frequency of diabetes, hypertension, dyslipidemia, time after replacement therapy, creatinine levels, and estimated glomerular filtration rate. In the CNI group, the observed and calculated AoR diameters were similar (P = 0.8). In the mTORi group, the observed AoR diameter was higher than the calculated one (P = 0.002). The concentric and eccentric left ventricular hypertrophy was similar in both groups (P = 0.12 and P = 0.69, respectively). In the stepwise regression analysis, the AoR diameter was associated with body surface area and mTORi treatment. CONCLUSIONS KTx recipients have a high prevalence of AoR dilation. Immunosuppressive regimen based on mTORi increases the incidence of AoR enlargement.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Seio Aórtico/patologia , Idoso , Inibidores de Calcineurina/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Cell Physiol Biochem ; 45(2): 547-557, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29402834

RESUMO

BACKGROUND/AIMS: Endothelial cell dysfunction is the principal pathological process underlying atherosclerotic cardiovascular disease. G protein-coupled receptor 124 (GPR124), an orphan receptor in the adhesion GPCR subfamily, promotes angiogenesis in the brain. In the present study, we explored the role of endothelial GPR124 in the development and progression of atherosclerosis in adult mice. METHODS: Using tetracycline-inducible transgenic systems, we generated mice expressing GPR124 specifically under control of the Tie-2 promoter. The animal model of atherosclerosis was constructed by intravenously injecting AAV-PCSK9DY into tetracycline-regulated mice and feeding the mice a high-fat diet for 16 consecutive weeks. Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of GPR124 in the pathological process of atherosclerosis. RESULTS: Higher TC (total cholesterol) and LDL-C (low density lipoprotein cholesterol) levels in serum and greater lipid deposition in the aortic sinus were found in atherosclerotic mice with GPR124 overexpression, coincident with the elevated proliferation of smooth muscle cells. We observed an elevation of ONOO- in the aortic sinus in this model by using immunofluorescence, and the experiments showed that the specific overexpression of GPR124 in the endothelium induced the up-regulation of CD68, NLRP3 and caspase-1 levels in the aortic sinus. CONCLUSION: The above results indicate that manipulating GPR124 in the endothelium may contribute to delayed pathological progression of atherosclerosis.


Assuntos
Aterosclerose/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aterosclerose/metabolismo , Caspase 1/metabolismo , Colesterol/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Humanos , Inflamação/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Peroxinitroso/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Receptores Acoplados a Proteínas-G/genética , Seio Aórtico/metabolismo , Seio Aórtico/patologia
13.
J Cardiothorac Surg ; 13(1): 12, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29347958

RESUMO

BACKGROUND: Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered. METHODS: Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the setting of Regression analysis, statistically significant differences among grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves analysis, threshold values for different grades were recognized. Grade 2 is identified in patients with AscA > 3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS: Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR.


Assuntos
Aorta/diagnóstico por imagem , Aorta/patologia , Estenose da Valva Aórtica/diagnóstico por imagem , Seio Aórtico/patologia , Idoso , Aorta/cirurgia , Valva Aórtica , Estenose da Valva Aórtica/cirurgia , Tomada de Decisão Clínica , Ecocardiografia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Curva ROC , Fatores de Risco , Seio Aórtico/diagnóstico por imagem
14.
Arterioscler Thromb Vasc Biol ; 38(3): 520-528, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29348121

RESUMO

OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background. Controls were chimeric Apoe-/- mice transplanted with bone marrow from Apoe-/- mice (wild type) and Vwf-/-Apoe-/- mice transplanted with bone marrow from Vwf-/-Apoe-/- mice (VWF-knock out). Susceptibility to atherosclerosis was evaluated in whole aortae and cross-sections of the aortic sinus in female mice fed a high-fat Western diet for 14 weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque size characterized by smaller necrotic cores, reduced neutrophil and monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2, and CX3CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant interstitial collagen (P<0.05 versus wild-type or EC-VWF mice). Atherosclerotic lesion size and composition were comparable between wild-type or EC-VWF mice. Together these findings suggest that EC-VWF, but not Plt-VWF, promotes atherosclerosis exacerbation. Furthermore, intravital microscopy experiments revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte adhesion under inflammatory conditions at the arterial shear rate. CONCLUSIONS: EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by promoting platelet adhesion and vascular inflammation. Plt-VWF even in the absence of a disintegrin and metalloprotease with thrombospondin type I repeats-13, both in platelet and plasma, was not sufficient to promote atherosclerosis.


Assuntos
Aorta/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , Doenças de von Willebrand/metabolismo , Fator de von Willebrand/metabolismo , Proteína ADAMTS13/genética , Proteína ADAMTS13/metabolismo , Animais , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Plaquetas/metabolismo , Transplante de Medula Óssea , Adesão Celular , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Endoteliais/patologia , Feminino , Leucócitos/metabolismo , Leucócitos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica , Adesividade Plaquetária , Seio Aórtico/metabolismo , Seio Aórtico/patologia , Doenças de von Willebrand/sangue , Doenças de von Willebrand/genética , Fator de von Willebrand/genética
17.
Pediatr Cardiol ; 39(3): 509-517, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29188316

RESUMO

Bicuspid aortic valve (BAV) is the most common congenital heart defect. BAV is associated with aortic stenosis and insufficiency, and aortic dilation in adult groups, but data in pediatric groups are limited. We sought to assess the impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients. We performed a retrospective review of all echocardiograms in patients with isolated BAV who were followed at our institution from July 2002 to July 2012. BAV morphology, aortic valve stenosis and/or insufficiency, and aortic dimensions were measured manually. Comparisons were made between right-left cusp fusion (RL) and right-noncoronary cusp fusion (RN) BAV morphologies. Generalized least square models were fit to analyze the impact of specific variables on aortic dilation. There were 1075 echocardiograms in 366 patients (72% male) with isolated BAV. Aortic valve insufficiency and stenosis were more common in RN (p < 0.001 for both). The median aortic sinus Z score was higher in the RL (0.47; IQR - 0.31 to 1.44) than in the RN group (0.02; - 0.83 to 0.82) (p < 0.001). There was no difference in median ascending aorta Z score between groups. Patients with the highest weights had larger aortas (p < 0.001), but the absolute difference between the highest and lowest weight groups was small (1.5 mm). The impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients presages that seen in adults. Patient body weight does not make significant clinical impacts on aortic diameters, suggesting that Z scores for aortic diameters should be based on ideal body weights.


Assuntos
Aorta/patologia , Insuficiência da Valva Aórtica/patologia , Estenose da Valva Aórtica/patologia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/patologia , Adolescente , Aorta/diagnóstico por imagem , Valva Aórtica/patologia , Criança , Pré-Escolar , Dilatação Patológica/patologia , Ecocardiografia , Feminino , Doenças das Valvas Cardíacas/congênito , Humanos , Lactente , Masculino , Estudos Retrospectivos , Seio Aórtico/patologia
18.
Arterioscler Thromb Vasc Biol ; 38(1): 26-39, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29162602

RESUMO

OBJECTIVE: Rosuvastatin has been widely used in the primary and secondary prevention of coronary heart disease. However, its antiatherosclerotic properties have not been tested in a mouse model that could mimic human coronary heart disease. The present study was designed to test the effects of rosuvastatin on coronary artery atherosclerosis and myocardial fibrosis in SR-B1 (scavenger receptor class B type 1) and apoE (apolipoprotein E) double knockout mice. APPROACH AND RESULTS: Three-week-old SR-B1-/-/apoE-/- mice were injected daily with 10 mg/kg of rosuvastatin for 2 weeks. Compared with saline-treated mice, rosuvastatin-treated mice showed increased levels of hepatic PCSK9 (proprotein convertase subtilisin/kexin type-9) and LDLR (low-density lipoprotein receptor) message, increased plasma PCSK9 protein but decreased levels of hepatic LDLR protein and increased plasma total cholesterol associated with apoB (apolipoprotein B) 48-containing lipoproteins. In spite of this, rosuvastatin treatment was associated with decreased atherosclerosis in both the aortic sinus and coronary arteries and reduced platelet accumulation in atherosclerotic coronary arteries. Cardiac fibrosis and cardiomegaly were also attenuated in rosuvastatin-treated SR-B1-/-/apoE-/- mice. Two-week treatment with rosuvastatin resulted in significant decreases in markers of oxidized phospholipids in atherosclerotic plaques. In vitro analysis showed that incubation of bone marrow-derived macrophages with rosuvastatin substantially downregulated cluster of differentiation (CD)36 and inhibited oxidized LDL-induced foam cell formation. CONCLUSIONS: Rosuvastatin protected SR-B1-/-/apoE-/- mice against atherosclerosis and platelet accumulation in coronary arteries and attenuated myocardial fibrosis and cardiomegaly, despite increased plasma total cholesterol. The ability of rosuvastatin to reduce oxidized phospholipids in atherosclerotic plaques and inhibit macrophage foam cell formation may have contributed to this protection.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Vasos Coronários/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Placa Aterosclerótica , Rosuvastatina Cálcica/farmacologia , Receptores Depuradores Classe B/deficiência , Seio Aórtico/efeitos dos fármacos , Animais , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/sangue , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Modelos Animais de Doenças , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Células Espumosas/patologia , Lipoproteínas LDL/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Knockout para ApoE , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/genética , Seio Aórtico/metabolismo , Seio Aórtico/patologia
20.
Clin Lab ; 63(10): 1627-1637, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29035447

RESUMO

BACKGROUND: The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has been proven to accelerate the development of atherosclerosis in apolipoprotein E (ApoE)-deficient mice. In this study, we used an ApoE knockout (ApoE-/-) mouse model with chronic intravenous infection with P. gingivalis to investigate the possible mechanisms of P. gingivalis-induced atherosclerosis. METHODS: Eight-week-old ApoE-/- mice were randomly assigned to two groups: (a) ApoE-/- + PBS (n = 8); (b) ApoE-/- + P. gingivalis (n = 8). Both of the groups received intravenous injections 3 times per week. After 4 weeks, oxidative stress mediators in serum, heart, aorta, and liver tissues were analyzed by using histology, ELISA, realtime PCR, and Western blot. RESULTS: Development of atherosclerosis as plaque formation in the aorta has been confirmed upon P. gingivalis infection. An abnormal lipid profile was found in the serum (increased amounts of very low-density lipoprotein [vLDL] and oxidized low-density lipoprotein [oxLDL], and decreased amount of HDL) and in some organs including heart, aorta or liver (increased mRNA levels of oxidized low-density lipoprotein receptor-1 [LOX-1] or fatty acid synthase [FAS]). Meanwhile, aggravated oxidative stress (higher level of reactive oxygen species [ROS] in the serum, and increased mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase [NOX]-2 and/or NOX-4 in the three organs) was observed, as well as enhanced inflammatory responses (increased expression and secretion of C-reactive protein [CRP] in the liver and serum, and increased mRNA levels of cyclooxygenase-2 [NOX-2] and/or inducible nitric oxide synthase [iNOS] in the three organs). Besides, inflammatory mediators including nuclear factor of kappa B (NF-κB) and iNOS showed increased protein levels in the three organs after P. gingivalis infection. CONCLUSIONS: These results suggest that chronic intravenous infection with P. gingivalis in ApoE-/- mice could accelerate the development of atherosclerosis, possibly associated with mediating oxidative stress as well as inflammatory responses and disturbing the lipid profile.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/microbiologia , Infecções por Bacteroidaceae/complicações , Porphyromonas gingivalis , Animais , Aterosclerose/enzimologia , Aterosclerose/patologia , Infecções por Bacteroidaceae/patologia , Inflamação/sangue , Lipídeos/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Seio Aórtico/patologia
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