RESUMO
BACKGROUND: Sclerostin (SC) is a monomeric glycoprotein expressed by osteocytes that affects bone formation. Recent studies have suggested a potential role for this protein in the pathophysiology of vascular diseases. The aim of the present study was to investigate SC expression in atherosclerotic plaques of patients affected by severe atherosclerotic disease who underwent carotid endarterectomy. We also evaluated possible differences in SC expression between patients with and without type 2 diabetes (T2D). METHODS: This was a cross-sectional study involving 46 patients aged 55 to 80 years (mean, 71.1 ± 6.7 years, 36 men, 15 patients with T2D) who underwent carotid endarterectomy. Immunohistochemical levels of SC were evaluated in the atherosclerotic plaques by double-staining immunochemistry, and serum SC levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Sclerostin was present in the atherosclerotic plaques of all subjects investigated and increased significantly in the media compared with the intima (P < 0.0001) as well as in vascular smooth muscle cells (VSMCs) compared with the infiltrating macrophages (P < 0.0001). However, no significant difference in SC expression was observed between patients with and without T2D. No correlation was found between serum and immunohistochemical levels of SC; significantly increased SC serum levels were detected in males compared with females (P = 0.049). CONCLUSIONS: We have demonstrated, for the first time, the expression of SC in VSMCs of atherosclerotic plaques, suggesting a potential role for this protein in the development of atherosclerosis. Further studies are needed to understand if the role played by SC is detrimental or protective in the atherosclerotic disease process.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Endarterectomia das Carótidas , Placa Aterosclerótica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismoRESUMO
BACKGROUND: The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis. METHODS: In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis. RESULTS: We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5-77.8) pg/mL and 43.89 (37.5-50.4), P < 0.001] and was significantly and independently associated with unstable plaque in patients with internal carotid artery stenosis [OR, 5,71 (95% CI, 2.09-15.29]. CONCLUSIONS: We have found, for the first time, that FGF23 could be associated with unstable plaque in type 2 diabetic patients with internal carotid artery stenosis.
Assuntos
Artéria Carótida Interna , Estenose das Carótidas/sangue , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/sangue , Placa Aterosclerótica/sangue , Idoso , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Diabetes Mellitus Tipo 2/complicações , Endarterectomia das Carótidas , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/cirurgia , Estudos Retrospectivos , Ultrassonografia DopplerRESUMO
OBJECTIVE: Atherosclerosis and vascular remodeling after injury are driven by inflammation and mononuclear cell infiltration. Unstable atherosclerotic plaques are characterized by a large necrotic core. In this study we investigated the distribution and interaction between gene polymorphisms encoding proinflammatory molecules in an Italian population with internal carotid artery stenosis (ICAS). We also evaluated whether reciprocal interaction between these gene polymorphisms increased the risk of plaque vulnerability. METHODS: In this genetic association study, 11 proinflammatory gene polymorphisms were analyzed in 933 individuals comprising 344 patients with ICAS who underwent carotid endarterectomy and 589 controls without ultrasound evidence of atherosclerosis or intimal thickening. RESULTS: We found that interleukin (IL) 6 (IL-6), IL-1ß, monocyte chemoattractant protein-1 (CCL2) macrophage inflammatory protein-1α (CCL3), E-selectin (SELE), intercellular adhesion molecule 1 (ICAM1), and matrix metalloproteinase-3 (MMP-3), and 9 (MMP-9) gene variants were independently and significantly associated with ICAS. The association remained significant even after the Bonferroni correction. We also found a genetic profile associated with different risks for ICAS, depending on the number of high-risk genotypes simultaneously present in an individual. Furthermore, proinflammatory genetic profiles are significantly more common in individuals with unstable carotid plaque. CONCLUSIONS: Our study shows, for the first time, a reciprocal interaction between proinflammatory genotypes for the development and progression of ICAS.
Assuntos
Artéria Carótida Interna/patologia , Estenose das Carótidas/genética , Mediadores da Inflamação , Inflamação/genética , Placa Aterosclerótica , Polimorfismo de Nucleotídeo Único , Idoso , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/imunologia , Estenose das Carótidas/cirurgia , Estudos de Casos e Controles , Progressão da Doença , Endarterectomia das Carótidas , Feminino , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Itália , Masculino , Fenótipo , Valor Preditivo dos Testes , Fatores de Risco , Ruptura EspontâneaRESUMO
Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients.
Assuntos
Aorta Torácica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Lesões do Sistema Vascular/cirurgia , Ferimentos não Penetrantes/cirurgia , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/lesões , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Intervalo Livre de Doença , Emergências , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Migração de Corpo Estranho/etiologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/mortalidade , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases. This study was designed to assess the association between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and plaque stability in patients with carotid atherosclerosis. METHODS: We studied 177 patients with internal carotid artery stenosis who underwent carotid endarterectomy and also 303 controls. Carotid endarterectomy samples removed from patients were assessed by immunohistochemistry. Concentrations of OPG were measured and gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis and were compared, initially between patients with carotid atherosclerosis and controls, and subsequently between stable and unstable carotid plaques. RESULTS: We found that the GG genotype of the T245G polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of the G1181C polymorphism were significantly higher in patients with carotid plaque than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and 20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L; P<0.01), which were significantly higher in patients with unstable atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01). CONCLUSIONS: The TNFRSF11B gene polymorphisms studied are associated with high serum OPG levels and might be potential markers for plaque instability.
Assuntos
Estenose das Carótidas/sangue , Estenose das Carótidas/genética , Predisposição Genética para Doença/genética , Osteoprotegerina/sangue , Osteoprotegerina/genética , Placa Aterosclerótica/sangue , Placa Aterosclerótica/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Aggressive, recurrent embolisms require accurate etiologic diagnosis. We describe the case of a 69-year-old Italian Caucasian woman with recurrent arterial embolisms in whom several sources and triggers of thrombosis were detected. CASE PRESENTATION: The patient, a 69-year-old Italian Caucasian woman, presented with a systemic embolism that was initially attributed to atrial fibrillation. The recurrence of embolisms despite anti-thrombotic therapy prompted a re-evaluation of the clinical presentation. New potential causes of thrombosis emerged in this patient, including thrombocytosis associated with the JAK2 V617F mutation and the very rare mural thrombosis of the descending aorta. A mural thrombus in the pulmonary artery was detected contiguous with the aortic mural thrombosis, raising the possibility of a clinically silent ductus Botalli as the initiating event. The patient was treated with warfarin, aspirin, hydroxyurea, and surgery. CONCLUSIONS: The diagnosis was achieved via systematic use of imaging procedures and reconsideration of blood tests performed to explore the diagnosis of thrombosis. This allowed a deeper and more detailed analysis of the case beyond the conventional approach, which would have aimed to identify one cause for the condition at hand, in this case, atrial fibrillation. The broader approach that we used resulted in the diagnosis of multiple embolisms from multiple sites and multiple causes.