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2.
Cell Mol Life Sci ; 78(9): 4161-4187, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33575814

RESUMO

A disintegrin and metalloproteases (ADAMs) are key mediators of cell signaling by ectodomain shedding of various growth factors, cytokines, receptors and adhesion molecules at the cellular membrane. ADAMs regulate cell proliferation, cell growth, inflammation, and other regular cellular processes. ADAM17, the most extensively studied ADAM family member, is also known as tumor necrosis factor (TNF)-α converting enzyme (TACE). ADAMs-mediated shedding of cytokines such as TNF-α orchestrates immune system or inflammatory cascades and ADAMs-mediated shedding of growth factors causes cell growth or proliferation by transactivation of the growth factor receptors including epidermal growth factor receptor. Therefore, increased ADAMs-mediated shedding can induce inflammation, tissue remodeling and dysfunction associated with various cardiovascular diseases such as hypertension and atherosclerosis, and ADAMs can be a potential therapeutic target in these diseases. In this review, we focus on the role of ADAMs in cardiovascular pathophysiology and cardiovascular diseases. The main aim of this review is to stimulate new interest in this area by highlighting remarkable evidence.


Assuntos
Proteínas ADAM/metabolismo , Proteína ADAM17/metabolismo , Doenças Cardiovasculares/patologia , Angiotensina II/metabolismo , Animais , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Doenças Cardiovasculares/metabolismo , Citocinas/metabolismo , Humanos , Hipertensão/metabolismo , Hipertensão/patologia , Transdução de Sinais
5.
Arterioscler Thromb Vasc Biol ; 40(9): 2195-2211, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698686

RESUMO

OBJECTIVE: To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS). Approach and Results: We performed single-cell RNA sequencing to study aortic root/ascending aneurysm tissue from Fbn1C1041G/+ (MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult Fbn1C1041G/+ mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE-/- mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 (Serpine1) and Kruppel-like factor 4 (Klf4). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of Fbn1C1041G/+ SMC/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young Fbn1C1041G/+ mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, suggesting activation of phenotype modulation. modSMCs were not found in nondilated adult Fbn1C1041G/+ descending thoracic aortas. Single-cell RNA sequencing from human MFS aortic root aneurysm tissue confirmed analogous SMC modulation in clinical disease. Enhanced expression of TGF-ß (transforming growth factor beta)-responsive genes correlated with SMC modulation in mouse and human data sets. CONCLUSIONS: Dynamic SMC phenotype modulation promotes extracellular matrix substrate modulation and aortic aneurysm progression in MFS. We characterize the disease-specific signature of modSMCs and provide temporal, transcriptomic context to the current understanding of the role TGF-ß plays in MFS aortopathy. Collectively, single-cell RNA sequencing implicates TGF-ß signaling and Klf4 overexpression as potential upstream drivers of SMC modulation.


Assuntos
Aneurisma Aórtico/genética , Fibrilina-1/genética , Perfilação da Expressão Gênica , Síndrome de Marfan/complicações , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Análise de Célula Única , Transcriptoma , Animais , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Predisposição Genética para Doença , Masculino , Síndrome de Marfan/genética , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/patologia , Mutação , Miócitos de Músculo Liso/patologia , Fenótipo , RNA-Seq , Fatores de Tempo , Remodelação Vascular/genética
6.
Surgery ; 168(1): 185-192, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32507629

RESUMO

BACKGROUND: Acute type A aortic dissection is a cardiovascular emergency requiring operative intervention. Despite advancements in operative technique and increased specialization of cardiovascular care, operative mortality, and morbidity after repair of type A aortic dissection remain high. Our aim was to assess national trends in outcomes of type A aortic dissection repair and the impact of institutional thoracic aortic repair volume on clinical outcomes and resource use in the United States. METHODS: Using the procedural and diagnostic codes of the International Classification of Diseases, Ninth Revision, we identified type A aortic dissection repairs from the 2005 to 2014 database of the National Inpatient Sample. Hospitals were classified into low-, medium- and high-volume tertiles based on annual incidence of thoracic aortic operations. Patient demographics and hospital characteristics, as well as outcomes including mortality, cost, and duration of stay, were evaluated using parametric tests for trends and the volume-outcome relationship. We used a multivariable-adjusted logistic regression model to identify factors associated with mortality. RESULTS: An estimated 25,231 patients received type A aortic dissection repair with an increasing temporal trend in volume and concomitant decrease in mortality. When stratified by hospital volume, 10,115 (40.1%), 8,194 (32.4%), and 6,920 (27.4%) underwent type A aortic dissection at low-volume, medium-volume, and high-volume, respectively. The unadjusted mortality rate in high-volume was the least (21.5% vs 16.8% vs 11.6% for low-volume, medium-volume, and high-volume, respectively; P < .001). Multivariable analysis revealed older age, lesser household incomes and comorbidities, including congestive heart failure (adjusted odds ratio 1.44; P < .001) and coagulopathy (adjusted odds ratio 1.33; P = .01) as statistically significant predictors of mortality; however, the risk-adjusted duration of stay (adjusted odds ratio 0.88; P = .06) was not different between low-volume and high-volume hospitals. After adjusting for patient and hospital characteristics, type A aortic dissection repair at low-volume hospitals was associated with increased likelihood of mortality compared with high-volume hospitals (adjusted odds ratio 2.10; P < .001). Patients undergoing type A aortic dissection repair at low-volume hospitals had increased odds of all complications including stroke, and respiratory complications compared than those at high-volume hospitals (P = .02, P < .001, and P < .001, respectively). CONCLUSION: The volume of open surgical repair for type A aortic dissection in the United States has increased over the past decade, while mortality has decreased. Hospital aortic operative volume is strongly associated with outcomes for type A aortic dissection repair. Protocols for expeditious transfer of patients to high volume aortic centers may serve to further decrease the acute mortality and complications of this procedure.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/cirurgia , Idoso , Aneurisma Dissecante/complicações , Aneurisma Dissecante/mortalidade , Aneurisma Dissecante/patologia , Aorta/patologia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/patologia , Feminino , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Ann Vasc Surg ; 69: 345-351, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32504789

RESUMO

BACKGROUND: Several studies in the literature report continued proximal aorta and distal iliac artery dilatation after surgical correction of an abdominal aortic aneurysm (AAA). The purpose of this study is to evaluate these findings, in a South American population, and relate them to the type of configuration of the open procedure aortic reconstruction. METHODS: This is a retrospective review of ultrasonographic follow-up of patients submitted to open repair of AAA from 1989 to 2013, reporting proximal aorta dilatation (≥3 cm) and distal iliac artery dilatation (≥1.5 cm). RESULTS: A total of 155 patients were included. Life-table freedom at the intervals 11 < 15 years and ≥15 years were 47% and 23% for proximal dilatation and 63% and 38% for distal iliac arteries dilatation, respectively. There were more proximal and distal dilatations in patients submitted to more extensive aortic reconstructions (aorto-aortic 13% and 22% vs aorto-bilateral common iliacs 27% and 8% vs aorto-unilateral or bilateral external iliacs 27% and 32% and aorto-femoral 67% and 0%) P < 0.0001. Juxtarenal anastomosis was also correlated with more proximal dilatations (42% vs 21%, P = 0,046). There were two proximal and three distal anastomosis pseudoaneurysms. CONCLUSIONS: The presence of more extensive degenerative disease at the time of operation, requiring juxtarenal or more distal iliac reconstructions, may pose an increased risk of proximal aorta and iliac artery dilatation during follow-up. This study corroborates that significant changes are found after 7 to 10 years of the operation, reinforcing the need for long-term monitoring.


Assuntos
Falso Aneurisma/patologia , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma Aórtico/patologia , Implante de Prótese Vascular/efeitos adversos , Artéria Ilíaca/cirurgia , Remodelação Vascular , Idoso , Idoso de 80 Anos ou mais , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/epidemiologia , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/epidemiologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/patologia , Brasil/epidemiologia , Dilatação Patológica , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/patologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Ann Vasc Surg ; 69: 352-359, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32502679

RESUMO

BACKGROUND: Management of uncomplicated type B aortic dissection (TBAD) has traditionally been aggressive medical therapy. Recent studies brought about a paradigm shift with evidence to suggest benefits from early endovascular intervention to a high risk subgroup of acute uncomplicated TBAD patients. AIMS: We aim to review the effects of aortic remodeling in Asian patients with TBAD with and without endovascular intervention, including maximal aortic diameter, true lumen diameter, and false lumen thrombosis. METHODS: This is a single-center retrospective study of a prospective database. Patients who presented to our institution with acute TBAD from January 2008 to December 2015 (n = 44) were evaluated. Eighteen percent (8 patients) presented with complicated TBAD and underwent emergency thoracic endovascular aortic repair (TEVAR) while the remaining 82% (36 patients) were treated with optimal medical therapy (OMT). RESULTS: Six patients under the conservative arm crossed over to elective TEVAR after 6 weeks because of interval radiological progression of disease. There was no significant difference in the baseline demographics of the TEVAR group and the OMT group. At 24 months, mean maximal aortic diameter difference was -7.7 mm and +1.9 mm (P = 0.077), mean true lumen diameter difference was +10.0 mm and +2.6 mm (P = 0.049), and false lumen thrombosis was 100% and 20% (P = 0.012) for TEVAR and OMT, respectively. Kaplan-Meier analysis showed no significant difference in mortality between the 2 groups at 30 days and 2 years. CONCLUSIONS: Within an Asian population with TBAD, TEVAR with OMT has a significant positive effect on aortic remodeling, compared with OMT-only management.


Assuntos
Aneurisma Dissecante/terapia , Aorta Torácica/cirurgia , Aneurisma Aórtico/terapia , Fármacos Cardiovasculares/uso terapêutico , Procedimentos Endovasculares , Remodelação Vascular , Idoso , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etnologia , Aneurisma Dissecante/patologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/etnologia , Aneurisma Aórtico/patologia , Grupo com Ancestrais do Continente Asiático , Fármacos Cardiovasculares/efeitos adversos , Bases de Dados Factuais , Emergências , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Singapura , Fatores de Tempo , Resultado do Tratamento
9.
Cardiovasc Pathol ; 47: 107209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32145675

RESUMO

Aneurysms in the sinuses of Valsalva (SVA) are the least frequent and occur due to a weakness in the aortic wall that forms part of the sinus. This causes dilatation and the formation of a blind pocket in one of the aortic sinuses (usually he right sinus and less frequently the posterior one). It may be congenital or acquired: in a congenital SVA, the condition is frequently associated with Marfan's syndrome or other connective tissue disorders; instead, acquired forms of sinus of Valsalva aneurysm are associated with infections (syphilis, bacterial endocarditis, and tuberculosis), atherosclerosis and medial cystic necrosis, traumatic and degenerative diseases, abuse of drugs or alcoholism. Despite SVA is a well-known anomaly, autopsy images or reviews of the condition are very uncommon. Indeed we report here a fatal case of SVA in a 58-year-old homeless man found dead on the street. The autopsy, performed to determine the cause of death, releaved a massive aneurysm (in excess of 4 cm) involving the right coronary sinus of the aorta. In this case, the aneurysm may be an accidental finding: in effect we found no tromboses inside the aneurysm and the ostium was not obstructed, therefore the cause of death could be attribuited to fatal arrhythmia.


Assuntos
Aneurisma Aórtico/patologia , Seio Aórtico/patologia , Dilatação Patológica , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
10.
BMC Cardiovasc Disord ; 20(1): 142, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192428

RESUMO

BACKGROUND: Ascending aortic aneurysms are one of the major causes of mortality. In recent years, there is a growing interest of epicardial adipose tissue (EAT) and related diseases. The aim of this study was to investigate the relationship of EAT, and PAT with ascending aortic dilatation (AAD). METHODS: We included 934 patients with hypertension in this study. The patients were evaluated by a complete transthoracic echocardiographic examination, including measurements of EAT, PAT, and aortic dimensions. Aortic size index (ASI) was used for diagnosing AAD. The patients were divided into two groups: dilated ascending aorta diameter (ASI ≥ 21 mm / m2, n = 102) or normal aortic diameter (ASI < 21 mm / m2, n = 832) according to the ASI. Characteristics of these patients were compared before and after propensity score matching analysis. RESULTS: Patients with AAD were older (72.3 ± 11.6 vs. 61.7 ± 12.7 years, p <  0.001), had more female gender (66% vs. 54%,p = 0.021) than patients with normal ascending aorta (AA). After propensity score matching analysis (77 vs. 77), EAT [OR:1.461, %95CI (1.082-1.974), p = 0.013] was independently associated with AAD in multivariate logistic regression analysis. In ROC curve analysis, EAT > 0.45 cm had 51.9% sensitivity and 62.3% specificity [AUC = 0.617, P = 0.012, 95% CI (0.529-0.707)]. CONCLUSION: Based on our findings, increased EAT may be suggested as an independent risk factor for AAD due to local or systemic effects in hypertensive patients.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Aorta/diagnóstico por imagem , Aneurisma Aórtico/etiologia , Ecocardiografia , Hipertensão/complicações , Remodelação Vascular , Idoso , Idoso de 80 Anos ou mais , Aorta/fisiopatologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Estudos Transversais , Dilatação Patológica , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Pericárdio , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
11.
Cardiovasc Pathol ; 46: 107206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32062108

RESUMO

Aortic lesions, such as an aortic aneurysm, are known as a late complication that usually occurs several years after the onset of giant cell arteritis. Here, we report a rare case of large-vessel giant cell arteritis in a patient with aortic dissection. A 71-year-old man presented with acute back pain and was diagnosed with aortic dissection, Stanford type A, and he underwent elective ascending aortic replacement. Further studies showed that the resected ascending aorta had aortic dissection and multinucleated giant cell granulomas; the granulomas were located in the media near the intima with partial destruction of the internal elastic lamina; there was no stenosis of the feeding blood vessel or fibrosis of the adventitia as observed in Takayasu arteritis; other types of vasculitis were considered unlikely based on the symptoms and laboratory data. The patient was further diagnosed with giant cell arteritis, which was classified as a large vessel vasculitis along with Takayasu arteritis at the Chapel Hill Consensus Conference in 2012. This is a rare case of giant cell arteritis diagnosed in a patient with aortic dissection. The differences in histopathological findings between Takayasu arteritis and giant cell arteritis are discussed.


Assuntos
Aneurisma Dissecante/etiologia , Aneurisma Aórtico/etiologia , Arterite de Células Gigantes/complicações , Idoso , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/patologia , Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Aneurisma Aórtico/cirurgia , Aortografia , Biópsia , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/patologia , Arterite de Células Gigantes/cirurgia , Humanos , Masculino , Arterite de Takayasu/patologia , Resultado do Tratamento
12.
Arterioscler Thromb Vasc Biol ; 40(3): e37-e46, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32101472

RESUMO

The aortic wall is composed of highly dynamic cell populations and extracellular matrix. In response to changes in the biomechanical environment, aortic cells and extracellular matrix modulate their structure and functions to increase aortic wall strength and meet the hemodynamic demand. Compromise in the structural and functional integrity of aortic components leads to aortic degeneration, biomechanical failure, and the development of aortic aneurysms and dissections (AAD). A better understanding of the molecular pathogenesis of AAD will facilitate the development of effective medications to treat these conditions. Here, we summarize recent findings on AAD published in ATVB. In this issue, we focus on the dynamics of aortic cells and extracellular matrix in AAD; in the next issue, we will focus on the role of signaling pathways in AAD.


Assuntos
Aneurisma Dissecante/patologia , Aorta/patologia , Aneurisma Aórtico/patologia , Matriz Extracelular/patologia , Aneurisma Dissecante/metabolismo , Aneurisma Dissecante/fisiopatologia , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/fisiopatologia , Dilatação Patológica , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Hemodinâmica , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Remodelação Vascular
13.
Cardiovasc Pathol ; 46: 107175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31951962

RESUMO

Aortic syphilis today is infrequently diagnosed clinically. Described herein are findings in 5 women who had resection of a fusiform aneurysm of the tubular portion of ascending aorta, and examination of the wall of the aneurysm disclosed classic features of aortic syphilis. The 5 patients were among 36 who had ascending aortic operations at Baylor University Medical Center in Dallas in 2018 and early 2019. Syphilitic aneurysm in each spared the sinus portion and involved diffusely the tubular portion of ascending aorta, beginning at the sinotubular junction. The aneurysmal wall was thicker than normal because of thickening of both intima and adventitia. The latter contained foci of lymphocytes and plasmacytes and thickened and narrowed vasa vasora. The media was disrupted by fibrous scars, which weakened the integrity of the aorta. Aortitis of the tubular portion of ascending aorta in syphilis is a diffuse process, but often is mistakenly called "atherosclerosis" which, when present in this portion of aorta, can be extensive but is focal. Aortic syphilis is important to diagnose so that patients can receive antibiotic therapy to delay, prevent, or treat neurosyphilis, a common accompaniment of aortic syphilis.


Assuntos
Aneurisma Infectado/microbiologia , Aorta/microbiologia , Aneurisma Aórtico/microbiologia , Aortite/microbiologia , Sífilis Cardiovascular/microbiologia , Idoso , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/patologia , Aneurisma Infectado/cirurgia , Antibacterianos/uso terapêutico , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Aneurisma Aórtico/cirurgia , Aortite/diagnóstico por imagem , Aortite/patologia , Aortite/cirurgia , Aortografia , Biópsia , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Fatores de Risco , Sífilis Cardiovascular/diagnóstico por imagem , Sífilis Cardiovascular/patologia , Sífilis Cardiovascular/cirurgia , Texas , Resultado do Tratamento
14.
Interact Cardiovasc Thorac Surg ; 30(3): 458-464, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800040

RESUMO

OBJECTIVES: Our aim was to compare aortic remodelling in type B dissections after thoracic endovascular aortic repair (TEVAR) or conservative treatment. METHODS: We conducted a retrospective analysis of computed tomography (CT) data sets at dissection onset and at the last follow-up in a group with conservative (group A) and TEVAR treatment (group B). An additional analysis of the preoperative CT images was performed in patients from group A, who were converted to TEVAR during follow-up. Diameters and lengths of all aortic segments were measured and growth rates were calculated. RESULTS: We included 74 patients: 50 patients in group A (follow-up time: 1625 ± 209 days) and 24 patients in group B (follow-up time: 554 ± 129 days). The mean aortic diameter growth rate was significantly higher in group A than in group B in the mid-descending aorta (A: +7 mm/year; B: -4 mm/year; P = 0.003). Length growth difference was only present in the abdominal aortic segment and was more pronounced in group A (+2 vs ±0 mm/year; P = 0.009). The conversion rate from conservative treatment to TEVAR was 36% (n = 18). A false lumen diameter of >22 mm at baseline was associated with a higher rate of conversion (P = 0.036). After conversion, the mean growth rate in the proximal descending and mid-descending aorta decreased from preoperative +11 and +18 mm/year to postoperative -9 and -14 mm/year, respectively (P < 0.001). CONCLUSIONS: In acute type B dissections, TEVAR stops aortic enlargement in the thoracic aorta, but promotes distal dilatation compared to the conservative treatment group. After conversion to TEVAR in conservatively pretreated chronic type B dissections, a more pronounced diameter decrease in the descending aorta was observed than in patients treated in the acute phase.


Assuntos
Aneurisma Dissecante/terapia , Aneurisma Aórtico/terapia , Tratamento Conservador , Procedimentos Endovasculares , Remodelação Vascular , Adulto , Idoso , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/patologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Implante de Prótese Vascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Cardiovasc Pathol ; 44: 107152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760245

RESUMO

A 74-year-old woman with severe aortic valve stenosis underwent aortic valve replacement with a pericardial bioprosthesis. Histological analysis of the excised valve showed dystrophic calcification associated with signs of healed infective endocarditis. Two months later, the patient died due to congestive heart failure. Autopsy revealed a bowel infarction and the presence of multiple mycotic aneurysms of the aortic root with mural thrombosis, which were unnoticed during the patient hospital stay and surgical window.


Assuntos
Aneurisma Infectado/microbiologia , Aneurisma Aórtico/microbiologia , Estenose da Valva Aórtica/cirurgia , Bioprótese/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Infecções Relacionadas à Prótese/microbiologia , Idoso , Aneurisma Infectado/patologia , Aneurisma Infectado/terapia , Aneurisma Aórtico/patologia , Aneurisma Aórtico/terapia , Autopsia , Causas de Morte , Evolução Fatal , Feminino , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Infecções por Klebsiella/patologia , Infecções por Klebsiella/terapia , Infecções Relacionadas à Prótese/patologia , Infecções Relacionadas à Prótese/terapia
16.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165587, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678158

RESUMO

Mechanisms whereby fibrillin-1 mutations determine thoracic aorta aneurysms/dissections (TAAD) in Marfan Syndrome (MFS) are unclear. Most aortic aneurysms evolve from mechanosignaling deregulation, converging to impaired vascular smooth muscle cell (VSMC) force-generating capacity accompanied by synthetic phenotype switch. However, little is known on VSMC mechanoresponses in MFS pathophysiology. Here, we investigated traction force-generating capacity in aortic VSMC cultured from 3-month old mg∆lpn MFS mice, together with morpho-functional and proteomic data. Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression. In parallel, the increased cell area and its complex non-fusiform shape suggested possible transition towards a mesenchymal-like phenotype, confirmed through several markers (e.g. N-cadherin, Slug). MFS-VSMC proteomic profile diverged from that of WT-VSMC particularly regarding lower expression of actin cytoskeleton-regulatory proteins. Accordingly, MFS-VSMC displayed lower traction force-generating capacity and impaired contractile moment at physiological substrate stiffness, and markedly attenuated traction force responses to enhanced substrate rigidity. Such impaired mechanoresponses correlated with decreased number, altered morphology and delocalization of focal adhesions, as well as disorganized actin stress fiber network vs. WT-VSMC. In VSMC cultured from 6-month-old mice, phenotype changes were attenuated and both WT-VSMC and MFS-VSMC generated less traction force, presumably involving VSMC aging, but without evident senescence. In summary, MFS-VSMC display impaired force-generating capacity accompanying a mesenchymal-like phenotype switch connected to impaired cytoskeleton/focal adhesion organization. Thus, MFS-associated TAAD involves mechanoresponse impairment common to other TAAD types, but through distinct mechanisms.


Assuntos
Síndrome de Marfan/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Actinas/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Biomarcadores/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Modelos Animais de Doenças , Feminino , Fibrilina-1/metabolismo , Adesões Focais/metabolismo , Adesões Focais/patologia , Masculino , Síndrome de Marfan/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , Proteômica/métodos
17.
J Surg Res ; 245: 1-12, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31394402

RESUMO

BACKGROUND: The process of aortic injury, repair, and remodeling during aortic aneurysm and dissection is poorly understood. We examined the activation of bone marrow (BM)-derived and resident aortic cells in response to aortic injury in a mouse model of sporadic aortic aneurysm and dissection. MATERIALS AND METHODS: Wild-type C57BL/6 mice were transplanted with green fluorescent protein (GFP)+ BM cells. For 4 wk, these mice were either unchallenged with chow diet and saline infusion or challenged with high-fat diet and angiotensin II infusion. We then examined the aortic recruitment of GFP+ BM-derived cells, growth factor production, and the differentiation potential of GFP+ BM-derived and GFP- resident aortic cells. RESULTS: Aortic challenge induced recruitment of GFP+ BM cells and activation of GFP- resident aortic cells, both of which produced growth factors. Although BM cells and resident aortic cells equally contributed to the fibroblast populations, we did not detect the differentiation of BM cells into smooth muscle cells. Interestingly, aortic macrophages were both of BM-derived (45%) and of non-BM-derived (55%) origin. We also observed a significant increase in stem cell antigen-1 (Sca-1)+ stem/progenitor cells and neural/glial antigen 2 (NG2+) cells in the aortic wall of challenged mice. Although some of the Sca-1+ cells and NG2+ cells were BM derived, most of these cells were resident aortic cells. Sca-1+ cells produced growth factors and differentiated into fibroblasts and NG2+ cells. CONCLUSIONS: BM-derived and resident aortic cells are activated in response to aortic injury and contribute to aortic inflammation, repair, and remodeling by producing growth factors and differentiating into fibroblasts and inflammatory cells.


Assuntos
Aneurisma Dissecante/patologia , Aorta/patologia , Aneurisma Aórtico/patologia , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/imunologia , Animais , Aorta/citologia , Aorta/imunologia , Aneurisma Aórtico/complicações , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Fibroblastos/imunologia , Fibroblastos/metabolismo , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/metabolismo
18.
Heart Lung Circ ; 29(2): 178-187, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31262619

RESUMO

Aortic dissection is a surgical emergency which poses a challenge to numerous clinicians across different specialties due to its high rate of associated morbidity and mortalities. Acute type A aortic dissection, which involves the ascending aorta and beyond, is a lethal condition. It is therefore vital to understand the pathophysiology that underlies this condition and the tools that aid its early detection. Haemodynamics factors including lumen wall shear stress and pressure, geometrical factors as entry tear location and size, and the composition of the aortic wall are well known to affect the disease progression. The studies on these factors are well established in Type B aortic dissection but not clearly emphasised in the setting of acute type A aortic dissection. The aim of this paper is to provide a comprehensive review of available literature on the relationship between tear size, location and the pressure of false lumen in acute type A aortic dissection.


Assuntos
Aneurisma Dissecante , Aorta , Aneurisma Aórtico , Pressão Sanguínea , Modelos Cardiovasculares , Resistência ao Cisalhamento , Aneurisma Dissecante/patologia , Aneurisma Dissecante/fisiopatologia , Aorta/patologia , Aorta/fisiopatologia , Aneurisma Aórtico/patologia , Aneurisma Aórtico/fisiopatologia , Feminino , Humanos , Masculino
19.
J Thorac Cardiovasc Surg ; 159(5): 1719-1726, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31272746

RESUMO

OBJECTIVE: Marfan syndrome (MFS) represents a genetic disorder with a range of clinical features, including proximal aortic aneurysms. Extensive research has revealed an abundance of transforming growth factor beta from a mutation in fibrillin-1 to be the key biochemical mechanism of aneurysm formation. Many important signaling pathways downstream of transforming growth factor beta have been further characterized. Our laboratory has previously demonstrated a unique murine model of MFS resulting in the accelerated formation of ascending aortic aneurysms and dilated cardiomyopathies. This study aims to characterize the relevance of this model to known signaling mechanisms in MFS. METHODS: Fibrillin 1C1039G/+ heterozygous mice (ie, MFS), with a mutation in fibrillin-1, were supplemented with 4.5 mg/kg/d angiotensin II to accelerate aneurysm formation. Four mouse groups were analyzed: wild type with or without angiotensin II and MFS with or without angiotensin II. Aortic tissue from these samples were subjected to western blotting and phosphoimaging to query various signaling pathways. RESULTS: Mice with MFS displayed downstream regulation in both the canonical (Smad2) and noncononical (extracellular signal-regulated kinases and P38) pathways characteristic of MFS. However, these downstream signals were exaggerated in the MFS mice supplemented with angiotensin II (accelerated model), matching the observed phenotypic severity of this model. CONCLUSIONS: The murine MFS model depicted here accelerates ascending aortic aneurysm formation and cardiomyopathies via well-characterized MFS signaling cascades. The mechanistic relevance of the accelerated murine MFS model suggests that it could be an important tool in future studies hoping to characterize MFS signaling in an expedited experimental design.


Assuntos
Aorta/metabolismo , Aneurisma Aórtico/metabolismo , Cardiomiopatias/metabolismo , Síndrome de Marfan/metabolismo , Miocárdio/metabolismo , Angiotensina II , Animais , Aorta/patologia , Aneurisma Aórtico/induzido quimicamente , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Cardiomiopatias/genética , Cardiomiopatias/patologia , Dilatação Patológica , Modelos Animais de Doenças , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrilina-1/genética , Predisposição Genética para Doença , Heterozigoto , Síndrome de Marfan/complicações , Síndrome de Marfan/genética , Camundongos Mutantes , Mutação , Miocárdio/patologia , Fenótipo , Fosforilação , Transdução de Sinais , Proteína Smad2/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Biomed Res Int ; 2020: 8306903, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33426065

RESUMO

Background: Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD. Methods: A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3'-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum TLR4 levels were collected from our previously published data. Results: We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164-0.939, P = 0.036; recessive model: OR = 0.439, 95%CI = 0.196-0.984, P = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382, 95%CI = 1.051-10.885, P = 0.041; dominant model: OR = 3.043, 95%CI = 1.041-8.900, P = 0.042). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD (P interaction = 0.038, OR = 15.229) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD (P = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers (P = 0.043). Conclusions: Our findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD.


Assuntos
Aneurisma Dissecante , Aneurisma Aórtico , Polimorfismo de Nucleotídeo Único/genética , Receptor 4 Toll-Like/genética , Adulto , Idoso , Aneurisma Dissecante/sangue , Aneurisma Dissecante/epidemiologia , Aneurisma Dissecante/genética , Aneurisma Dissecante/patologia , Aorta/patologia , Aneurisma Aórtico/sangue , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Estudos de Casos e Controles , China , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 4 Toll-Like/sangue
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