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1.
Sci Rep ; 12(1): 19163, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357433

RESUMO

Functional implications of left ventricular (LV) morphological characterization in congenital heart disease are not widely explored. This study qualitatively and quantitatively assessed LV shape associations with a) LV function and b) thoracic aortic morphology in patients with aortic coarctation (CoA) with/without bicuspid aortic valve (BAV), and healthy controls. A statistical shape modelling framework was employed to analyse three-dimensional (3D) LV shapes from cardiac magnetic resonance (CMR) data in isolated CoA (n = 25), CoA + BAV (n = 30), isolated BAV (n = 30), and healthy controls (n = 25). Average 3D templates and deformations were computed. Correlations between shape data and CMR-derived morphometric parameters (i.e., sphericity, conicity) or global and apical strain values were assessed to elucidate possible functional implications. The relationship between LV shape features and arch architecture was also explored. The LV template was shorter and more spherical in CoA patients. Sphericity was overall associated with global and apical radial (p = 0.001, R2 = 0.09; p < 0.0001, R2 = 0.17) and circumferential strain (p = 0.001, R2 = 0.10; p = 0.04, R2 = 0.04), irrespective of the presence of aortic stenosis and/or regurgitation and controlling for age and hypertension status. LV strain was not associated with arch architecture. Differences in LV morphology were observed between CoA and BAV patients. Increasing LV sphericity was associated with reduced strain, independent of aortic arch architecture and functional aortic valve disease.


Assuntos
Coartação Aórtica , Doença da Válvula Aórtica Bicúspide , Humanos , Valva Aórtica/patologia , Aorta/patologia , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Esquerda , Coenzima A
2.
Biosens Bioelectron ; 218: 114747, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36198238

RESUMO

Thoracic aortic aneurysm (TAA), in which arteries enlarge asymptomatically over time until dissection or rupture occurs, is a serious health risk. The mainstay of TAA treatment remains surgical repair due to the lack of effective drugs. The complex etiology and pathogenesis of TAA, including hemodynamic alterations and genetic factors, lead to inaccuracies in preclinical models for drug screening. Previously, our group designed an aorta smooth muscle-on-a-chip to emulate human aorta physiology and pathophysiology and screened three promising therapeutic drugs targeting mitochondrial dynamics in TAA. On this foundation, we updated the one-channel chip to an eighteen-well chip platform with four polydimethylsiloxane layers. Benefiting from this high-throughput chip, we rapidly screened multiple drugs simultaneously using distinct cell lines in vitro. In addition, we observed the abnormal activation of hypoxia-inducible factor 1-alpha (HIF-1alpha) in aortas from TAA patients by Western blot and bioinformatics analyses. Intriguingly, this phenomenon was replicated only when smooth muscle cells (SMCs) were strained on the chip. We then screened seven specific HIF-1alpha inhibitors and selected the two most effective drugs (2-methoxyestradiol and digoxin) by quantitative PCR and colorimetric methods. The results demonstrated that these two drugs can improve respiratory chain function and rescue the SMC contractile phenotype, showing applicability for the clinical treatment of TAA. This high-throughput aorta smooth muscle-on-a-chip will become a potential preclinical model for TAA drug screening.


Assuntos
Aneurisma da Aorta Torácica , Técnicas Biossensoriais , Humanos , Aneurisma da Aorta Torácica/tratamento farmacológico , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/metabolismo , 2-Metoxiestradiol/metabolismo , Avaliação Pré-Clínica de Medicamentos , Dispositivos Lab-On-A-Chip , Aorta/metabolismo , Aorta/patologia , Digoxina , Dimetilpolisiloxanos , Fator 1 Induzível por Hipóxia/metabolismo , Músculo Liso/metabolismo , Músculo Liso/patologia
3.
Leg Med (Tokyo) ; 59: 102154, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36191411

RESUMO

A male in his 90 s consulted a doctor because he experienced several days of general fatigue and dyspnea. He was diagnosed with heart failure, and diuretic medications taken for 3 days relieved his symptoms. However, he was found dead on the morning of the fourth day after consultation. He had received a third dose of coronavirus disease 2019 (COVID-19) vaccine approximately 2 weeks before death. An autopsy revealed dissection of the ascending aorta and pericardial hemotamponade. The heart showed a white villous surface, and the pericardium was fibrously thick. Microscopic examination revealed pericarditis with predominantly macrophage and lymphocyte infiltration. These histological findings were compatible with those of post-vaccination myocarditis. To the best of our knowledge, histopathologically proven pericarditis after COVID-19 vaccination has not been reported. In the present case, extended inflammation of the aortic adventitia was a possible cause of aortic wall fragility followed by dissection.


Assuntos
Aneurisma Dissecante , COVID-19 , Miocardite , Pericardite , Masculino , Humanos , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Autopsia , RNA Mensageiro , Pericardite/etiologia , Pericardite/patologia , Aneurisma Dissecante/etiologia , Aorta/patologia , Miocardite/complicações , Inflamação/complicações , Inflamação/patologia , Vacinação , Diuréticos
4.
Ter Arkh ; 94(5): 695-703, 2022 Jun 17.
Artigo em Russo | MEDLINE | ID: mdl-36286971

RESUMO

This article describes the various forms of inflammatory lesions of the aorta and large arteries, including chronic periaortitis, as well as the diagnostic methods are considered. Large vessel vasculitis represent the most common entities, however, there is also an association with other rheumatological or inflammatory diseases, drug-induced or paraneoplastic entities. Instrumental imaging modalities play an important role in the diagnosis.


Assuntos
Arterite de Células Gigantes , Doenças não Transmissíveis , Arterite de Takayasu , Humanos , Arterite de Takayasu/complicações , Arterite de Células Gigantes/diagnóstico , Aorta/diagnóstico por imagem , Aorta/patologia , Artérias/patologia
5.
Rom J Morphol Embryol ; 63(1): 71-82, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074670

RESUMO

AIM: The authors aimed to evaluate the correlations between the variation of two of the main morphological parameters of the aortic wall (intima and media thicknesses) and ageing. MATERIALS AND METHODS: Aortic cross sections (base region, cross region, thoracic region, and abdominal region) were collected from 90 cases of all ages died and autopsied in the hospital. Tissue samples were processed using the classical histopathological technique (formalin fixation and paraffin embedding) and stained with Orcein and Goldner's trichrome. The obtained histological slides were transformed into virtual slides. Intima and media thicknesses were determined on virtual slides using a custom-made software, developed in MATLAB (MathWorks, USA). RESULTS AND DISCUSSIONS: The intima layer underwent an obvious and continuous process of thickening both from the aortic base region to its terminal (abdominal) region and from young ages to old age. The processes were similar in men and women but almost always more pronounced in men than in women. The media layer underwent a thickness reduction process from the aortic base to the terminal (abdominal) region whereas with age, the thickness of the layer increased. This divergent profile of evolution was similar in both men and women but with some variations depending on either topography or ageing. CONCLUSIONS: Each of the main layers of the aortic wall revealed dynamic individual evolutionary profiles related to age, gender and topography along the aortic path. Studies must be continued in a more detailed, standardized and integrated way.


Assuntos
Envelhecimento , Aorta , Aorta/patologia , Autopsia , Feminino , Humanos , Masculino
6.
Biometals ; 35(6): 1325-1339, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36178540

RESUMO

Vascular calcification (VC) has been associated with a risk of cardiovascular diseases. Iron may play a critical role in progressive VC. Therefore, we investigated the effects of iron overload on the aorta of rats. A rat model of iron overload was established by intraperitoneal injection of Iron-Dextran. The levels of iron, calcium, and ALP activity were detected. Von Kossa staining and Perl's staining were conducted. The expression of iron metabolism-related and calcification related factors were examined in the aortic tissue of rats. The results showed serum and aortic tissue iron were increased induced by iron overload and excessive iron induced hepatic and renal damage. In iron overload rats, the expression of divalent metal transporter 1 (DMT1) and hepcidin were higher, but ferroportin1 (FPN1) was lower. Von Kossa staining demonstrated calcium deposition in the aorta of iron overload rats. The calcium content and ALP activity in serum and aortic tissue were increased and iron level in aortic tissue highly correlated with calcium content and ALP activity. The expressions of the osteogenic markers were increased while a decrease of Alpha-smooth muscle actin (α-SMA) in the aortic tissue of iron overload rats. IL-24 was increased during the calcification process induced by iron. Overall, we demonstrated excessive iron accumulation in the aortic tissue and induced organs damage. The iron metabolism-related factors were significantly changed during iron overload. Moreover, we found that iron overload leads to calcium deposition in aorta, playing a key role in the pathological process of VC by mediating osteoblast differentiation factors.


Assuntos
Sobrecarga de Ferro , Calcificação Vascular , Ratos , Animais , Cálcio/metabolismo , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , Sobrecarga de Ferro/metabolismo , Aorta/metabolismo , Aorta/patologia , Rim/metabolismo , Ferro/metabolismo
7.
Arterioscler Thromb Vasc Biol ; 42(11): 1355-1374, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36172868

RESUMO

BACKGROUND: Mural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue. METHODS: Single-nuclear RNA sequencing was performed on 13 samples from human donors, 6 with thoracic aortic aneurysm, and 7 without aneurysm. Individual transcriptomes were then clustered based on transcriptional profiles. Clusters were used for between-disease differential gene expression analyses, subcluster analysis, and analyzed for intersection with genetic aortic trait data. RESULTS: We sequenced 71 689 nuclei from human thoracic aortas and identified 14 clusters, aligning with 11 cell types, predominantly vascular smooth muscle cells (VSMCs) consistent with aortic histology. With unbiased methodology, we found 7 vascular smooth muscle cell and 6 fibroblast subclusters. Differentially expressed genes analysis revealed a vascular smooth muscle cell group accounting for the majority of differential gene expression. Fibroblast populations in aneurysm exhibit distinct behavior with almost complete disappearance of quiescent fibroblasts. Differentially expressed genes were used to prioritize genes at aortic diameter and distensibility genome-wide association study loci highlighting the genes JUN, LTBP4 (latent transforming growth factor beta-binding protein 1), and IL34 (interleukin 34) in fibroblasts, ENTPD1, PDLIM5 (PDZ and LIM domain 5), ACTN4 (alpha-actinin-4), and GLRX in vascular smooth muscle cells, as well as LRP1 in macrophage populations. CONCLUSIONS: Using nuclear RNA sequencing, we describe the cellular diversity of healthy and aneurysmal human ascending aorta. Sporadic aortic aneurysm is characterized by differential gene expression within known cellular classes rather than by the appearance of novel cellular forms. Single-nuclear RNA sequencing of aortic tissue can be used to prioritize genes at aortic trait loci.


Assuntos
Aneurisma da Aorta Torácica , Aneurisma Aórtico , Humanos , Estudo de Associação Genômica Ampla , Músculo Liso Vascular/metabolismo , Actinina/genética , RNA Nuclear/metabolismo , Aorta/patologia , Miócitos de Músculo Liso/metabolismo , Aneurisma da Aorta Torácica/patologia , Aneurisma Aórtico/metabolismo , Análise de Sequência de RNA , Fator de Crescimento Transformador beta/metabolismo
8.
J Am Coll Cardiol ; 80(8): 832-844, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35981827

RESUMO

Inflammatory aortitis is most often caused by large vessel vasculitis (LVV), including giant cell arteritis, Takayasu's arteritis, immunoglobulin G4-related aortitis, and isolated aortitis. There are distinct differences in the clinical presentation, imaging findings, and natural history of LVV that are important for the cardiovascular provider to know. If possible, histopathologic specimens should be obtained to aide in accurate diagnosis and management of LVV. In most cases, corticosteroids are utilized in the acute phase, with the addition of steroid-sparing agents to achieve disease remission while sparing corticosteroid toxic effects. Endovascular and surgical procedures have been described with success but should be delayed until disease control is achieved whenever possible. Long-term management should include regular follow-up with rheumatology and surveillance imaging for sequelae of LVV.


Assuntos
Aortite , Arterite de Células Gigantes , Arterite de Takayasu , Aorta/patologia , Aortite/diagnóstico por imagem , Aortite/terapia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Imunoglobulina G , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/patologia , Arterite de Takayasu/terapia
9.
Virchows Arch ; 481(5): 731-738, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35982277

RESUMO

Medial degeneration is the most common histological finding in ascending aortic aneurysms with lesser but significant involvement by atherosclerosis. The overall extent and severity can be potentially underrated because of their uneven distribution and macroscopic inconspicuousness of medial degeneration. This study aims to compare the distribution of degenerative and atherosclerotic lesions around ascending aorta circumference, also considering aortic valve cuspidity. We evaluated 88 cases of resected ascending aortae, 25 with a tricuspid aortic valve and 63 with a malformed aortic valve, oriented by a cardiac surgeon and sent for pathological examination. We applied the consensus documents from 2015 and 2016 for microscopic evaluation of aortic specimens. The medial degeneration and atherosclerosis were graded semi-quantitatively for each aortic quadrant: convexity, anterior wall, concavity, and posterior wall. Nearly all quadrants showed at least mild medial degeneration; more severe findings of medial degeneration and atherosclerosis were in the aneurysms associated with the tricuspid valve. In the aneurysms with the tricuspid aortic valve, there was more frequent and more severe atherosclerosis at the concavity than at the anterior wall (p = .046); the frequency and severity of medial degeneration did not differ significantly. The aneurysms with a malformed aortic valve showed more severe medial degeneration at the concavity compared to the convexity (p = .011); atherosclerosis was less common and did not show any significant differences. More than half of the samples also revealed at least a one-grade (mostly one-grade) difference among the quadrants in individual cases for both atherosclerosis and medial degeneration. Extreme differences were rare except for atherosclerosis in the tricuspid group. The results revealed only slight overall differences around the aortic circumference, with concavity being the most susceptible. Still, thanks to occurring inter- and intraindividual variability, the examination of all quadrants seems meaningful not to miss the most severe changes and to underscore the findings.


Assuntos
Aneurisma Aórtico , Aterosclerose , Humanos , Aneurisma Aórtico/complicações , Aneurisma Aórtico/patologia , Aorta/patologia , Valva Aórtica/patologia , Aterosclerose/complicações , Aterosclerose/patologia
10.
Curr Opin Lipidol ; 33(5): 271-276, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35979994

RESUMO

PURPOSE OF REVIEW: To highlight recent conceptual and technological advances that have positioned the field to interrogate the cellular and molecular mechanisms contributing to the initiation of atherosclerosis, including intimal lipid accumulation, inflammation, and lesion growth. RECENT FINDINGS: Advances in the understanding of endothelial LDL transcytosis and rapid lipid uptake by intimal macrophages provide mechanistic insights into intimal LDL accumulation and the initiation of atherogenesis. Recent studies have used unbiased single-cell approaches, such as single-cell RNA sequencing and CyTOF, to characterize the cellular components of the normal intima and atherosclerotic lesions. In-vitro studies and high-resolution transcriptomic analysis of aortic intimal lipid-loaded versus lipid-poor myeloid populations in vivo suggest that lipid-loaded macrophages may not be the primary drivers of inflammation in atherosclerotic lesions. SUMMARY: A new perspective on the complex cellular landscape of the aorta, specifically the atherosclerosis-prone regions, confirm that intimal accumulation of lipid, monocyte recruitment, and macrophage accumulation are key events in atherogenesis triggered by hypercholesterolemia. Targeting these early events may prove to be a promising strategy for the attenuation of lesion development; however, the specific details of how hypercholesterolemia acts to initiate early inflammatory events remain to be fully elucidated.


Assuntos
Aterosclerose , Hipercolesterolemia , Aorta/patologia , Aterosclerose/genética , Aterosclerose/patologia , Humanos , Hipercolesterolemia/patologia , Inflamação/patologia , Lipídeos
11.
Sci Rep ; 12(1): 12931, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902665

RESUMO

Testosterone deficiency in men is associated with increased atherosclerosis burden and increased cardiovascular risk. In male mice, testosterone deficiency induced by castration increases atherosclerosis as well as mature B cell numbers in spleen. As B cells are potentially pro-atherogenic, we hypothesized that there may be a link between these effects. To address whether mature B cell deficiency alter the atherogenic response to castration, we studied B cell-deficient µMT and genotype control male mice on an atherosclerosis-prone Apoe-/- background that were castrated or sham-operated pre-pubertally and fed a high-fat diet between 8 and 16 weeks of age to accelerate atherosclerosis development. Genotype did not affect the effects of castration on body weight or weights of fat depots and there were no differences in serum cholesterol levels across the four groups. Atherosclerosis assessed by quantification of lesion area in serial sections of the aortic root was significantly increased by castration and by the µMT mutation, with no significant interaction between genotype and surgery. In conclusion, castration evokes a similar atherogenic response in B cell-deficient µMT and control mice. These data suggest that atherogenesis following castration is unrelated to the effects of androgens on mature B cell numbers.


Assuntos
Aterosclerose , Animais , Aorta/patologia , Apolipoproteínas E , Aterosclerose/genética , Linfócitos B/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Orquiectomia , Testosterona/efeitos adversos
12.
J Am Coll Cardiol ; 80(5): 486-497, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35902171

RESUMO

BACKGROUND: The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined the genetics of thoracic aortic diameter in a single plane. OBJECTIVES: We sought to elucidate the genetic basis for the diameter of the LVOT, aortic root, and ascending aorta. METHODS: Using deep learning, we analyzed 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at 6 locations of ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these scores and disease incidence. RESULTS: A total of 79 loci were significantly associated with at least 1 diameter. Of these, 35 were novel, and most were associated with 1 or 2 diameters. A polygenic score of aortic diameter approximately 13 mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm (n = 427,016; mean HR: 1.42 per SD; 95% CI: 1.34-1.50; P = 6.67 × 10-21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n = 426,502; mean HR: 1.08 per SD; 95% CI: 1.03-1.12; P = 5 × 10-6). CONCLUSIONS: We detected distinct genetic loci underpinning the diameters of the LVOT, aortic root, and at several segments of ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding genetic contributions to proximal aortic diameter may enable identification of individuals at risk for aortic disease and facilitate prioritization of therapeutic targets.


Assuntos
Aneurisma , Aneurisma da Aorta Torácica , Estenose da Valva Aórtica , Aorta/diagnóstico por imagem , Aorta/patologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/genética , Estenose da Valva Aórtica/genética , Constrição Patológica , Estudo de Associação Genômica Ampla , Humanos
13.
J Mol Cell Cardiol ; 171: 30-44, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35843061

RESUMO

Enzymatic degradation of elastin by matrix metalloproteinases (MMPs) leads to the permanent dilation of aortic wall and constitutes the most prominent characters of aortic aneurysm and aging-related medial degeneration. Hydrogen sulfide (H2S) as a gasotransmitter exhibits a wide variety of cardio-protective functions through its anti-inflammatory and anti-oxidative actions. Cystathionine gamma-lyase (CSE) is a main H2S-generating enzyme in cardiovascular system. The regulatory roles of CSE/H2S system on elastin homeostasis and blood vessel degeneration have not yet been explored. Here we found that aged CSE knockout mice had severe aortic dilation and elastic degradation in abdominal aorta and were more sensitive to angiotensin II-induced aortic elastolysis and medial degeneration. Administration of NaHS would protect the mice from angiotensin II-induced inflammation, gelatinolytic activity, elastin fragmentation, and aortic dilation. In addition, human aortic aneurysm samples had higher inflammatory infiltration and lower expression of CSE. In cultured smooth muscle cells (SMCs), TNFα-induced MMP2/9 hyperactivity and elastolysis could be attenuated by exogenously applied NaHS or CSE overexpression while further deteriorated by complete knockout of CSE. It was further found that H2S inhibited MMP2 transcription by posttranslational modification of Sp1 via S-sulfhydration. H2S also directly suppressed MMP hyperactivity by S-sulfhydrating the cysteine switch motif. Taken together, this study revealed the involvement of CSE/H2S system in the pathogenesis of aortic elastolysis and medial degeneration by maintaining the inactive form of MMPs, suggesting that CSE/H2S system can be a target for the prevention of age-related medial degeneration and treatment of aortic aneurysm.


Assuntos
Aorta , Cistationina gama-Liase , Gasotransmissores , Sulfeto de Hidrogênio , Angiotensina II , Animais , Aorta/patologia , Cistationina gama-Liase/genética , Cisteína/metabolismo , Elastina , Humanos , Sulfeto de Hidrogênio/farmacologia , Metaloproteinase 2 da Matriz , Camundongos , Camundongos Knockout , Sulfetos , Fator de Necrose Tumoral alfa
14.
Int J Mol Sci ; 23(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806336

RESUMO

Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.


Assuntos
Aterosclerose , Células Progenitoras Endoteliais , Ftalazinas , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Lipoproteínas LDL/metabolismo , Fígado/metabolismo , Camundongos , Ftalazinas/farmacologia , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/metabolismo
15.
Curr Opin Cardiol ; 37(6): 446-453, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35880457

RESUMO

PURPOSE OF REVIEW: Type A intramural hematoma (TAIMH) is an acute aortic disease characterized by the presence of hematoma in the aortic media and involving the ascending aorta. Open repair seems to be the first treatment approach, although recent evidence highlights that the best management of TAIMH is controversial. This review will focus on the current concept for TAIMH management and factors affecting the decision making. RECENT FINDINGS: Recent studies have evaluated the role of open and endovascular repair, as well as conservative management in patients with TAIMH. More specific imaging findings seem to affect decision making for urgent repair. SUMMARY: Despite TAIMH's acute nature, conservative management seems to represent a valid option for urgent approach, presenting similar mortality to open and endovascular repair. Comparative data are limited, however, in experienced centers, any approach may be applied with encouraging results. Endovascular management, which is mainly applied to manage retrograde TAIMH, is related to lower mortality and morbidity compared to open repair in this group of patients while aortic remodeling seems beneficial with this approach. Imaging findings, as ulcer-like lesions, hematoma thickness, concomitant dissection and aortic diameter, related to higher complication rate, set the indication for interventional management. Further research, including prospective data and registries, and ideally, randomized data may further clarify the best approach and factors indicating urgent repair.


Assuntos
Doenças da Aorta , Implante de Prótese Vascular , Procedimentos Endovasculares , Doença Aguda , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta/cirurgia , Doenças da Aorta/diagnóstico , Doenças da Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Hematoma/etiologia , Hematoma/cirurgia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
16.
Eur J Cardiothorac Surg ; 62(2)2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35775901

RESUMO

A 70-year-old woman with heart failure and end-stage renal disease on dialysis was found to have a 2.9 cm × 0.9 cm swinging mass attached to the posterior wall of the ascending aorta, 3 cm above the aortic valve. Due to the risk of embolization, she underwent an aortotomy and mass excision. The mass had extensive calcifications with degenerative changes and no evidence of malignancy. This represents an exceedingly rare location for a calcified amorphous tumour. Our review adds to the literature establishing the proximal aorta as a characterized location for a calcified amorphous tumour and provides a treatment approach to prevent embolization.


Assuntos
Estenose da Valva Aórtica , Calcinose , Implante de Prótese de Valva Cardíaca , Neoplasias , Idoso , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Calcinose/cirurgia , Feminino , Humanos , Neoplasias/cirurgia
17.
J Vis Exp ; (185)2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35876556

RESUMO

Conventional two-dimensional cell culture techniques and animal models have been used in the study of human thoracic aortic aneurysm and dissection (TAAD). However, human TAAD sometimes cannot be characterized by animal models. There is an apparent species gap between clinical human studies and animal experiments that may hinder the discovery of therapeutic drugs. In contrast, the conventional cell culture model is unable to simulate in vivo biomechanical stimuli. To this end, microfabrication and microfluidic techniques have developed greatly in recent years, providing novel techniques for establishing organoids-on-a-chip models that replicate the biomechanical microenvironment. In this study, a human aorta smooth muscle cell organ-on-a-chip (HASMC-OOC) model was developed to simulate the pathophysiological parameters of aortic biomechanics, including the amplitude and frequency of cyclic strain experienced by human aortic smooth muscle cells (HASMCs) that play a vital role in TAAD. In this model, the morphology of HASMCs became elongated in shape, aligned perpendicularly to the strain direction, and presented a more contractile phenotype under strain conditions than under static conventional conditions. This was consistent with the cell orientation and phenotype in native human aortic walls. Additionally, using bicuspid aortic valve-related TAAD (BAV-TAAD) and tricuspid aortic valve-related TAAD (TAV-TAAD) patient-derived primary HASMCs, we established BAV-TAAD and TAV-TAAD disease models, which replicate HASMC characteristics in TAAD. The HASMC-OOC model provides a novel in vitro platform that is complementary to animal models for further exploring the pathogenesis of TAAD and discovering therapeutic targets.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Doença da Válvula Aórtica Bicúspide , Aneurisma Dissecante/genética , Aneurisma Dissecante/patologia , Animais , Aorta/patologia , Aorta Torácica/patologia , Valva Aórtica/patologia , Humanos , Dispositivos Lab-On-A-Chip , Miócitos de Músculo Liso/patologia
18.
Int. j. morphol ; 40(3): 697-705, jun. 2022. ilus, tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1385688

RESUMO

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.


RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.


Assuntos
Animais , Ratos , Aorta/efeitos dos fármacos , Doenças da Aorta/induzido quimicamente , Glutamato de Sódio/toxicidade , Vitamina E/farmacologia , Aorta/patologia , Glutamato de Sódio/administração & dosagem , Vitamina E/administração & dosagem , Microscopia Eletrônica , Interleucina-6/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Malondialdeído/antagonistas & inibidores
19.
BMC Cardiovasc Disord ; 22(1): 254, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668381

RESUMO

BACKGROUND: Thoracic aortic aneurysm (TAA), is a pathological dilatation of the aortic segment with the tendency to expand, dissect or rupture, and risk of mortality. The progression rate is mainly slow. As the risk of rupture increases with the size of the aortic diameter, it is important to diagnose TAA appropriately to prevent mortality. CASE PRESENTATION: Here, we present a case with a fast-growing TAA, complicated by subclinical dissection in a middle-aged gentleman, associated with non-compaction left ventricle, diagnosed 6 months after the first diagnosis of this co-occurrence, successfully managed by an uneventful surgical procedure. The pathological examination was the key to the diagnosis of this concealed phenomenon, i.e. a fast-growing aortic aneurysm complicated by subclinical dissection. CONCLUSION: This case report emphasizes the importance of close follow-up of patients with fast-growing TAA for considering remote possibility of this silent life-threatening disease; subclinical dissecting aneurysm, especially in patients with other cardiac comorbidities. Although imaging modalities can help accurate diagnosis, in cases with fast-growing TAA, we should not wait for imaging signs of dissection and/or rupture.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Aneurisma Dissecante/complicações , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/cirurgia , Aorta/patologia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Dilatação Patológica/complicações , Seguimentos , Humanos , Pessoa de Meia-Idade
20.
Semin Ultrasound CT MR ; 43(3): 204-220, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35688532

RESUMO

Imaging of the thoracic aorta is a common request in both the acute and outpatient settings, playing a crucial role in diagnosis and treatment planning of aortic disease. The findings of aortic pathology may be obvious or occult on imaging. Recognizing subtle changes is essential and may lead to early detection and prevention of serious morbidity and mortality. Knowledge of the anatomy and understanding the pathophysiology of aortic disease, as well as selecting the appropriate imaging modality and protocol will enable prompt diagnosis and early intervention of aortic pathology. Currently, computed tomography angiography and magnetic resonance angiography of the aorta are the most commonly used imaging modalities to evaluate the aorta. This review focuses on a spectrum of aortic pathology manifestations on computed tomography and magnetic resonance, including atherosclerosis and acute aortic syndromes, highlighting diagnostic challenges and approaches to aid in image interpretation.


Assuntos
Doenças da Aorta , Doenças Torácicas , Aorta/patologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Humanos , Angiografia por Ressonância Magnética , Tomografia Computadorizada por Raios X
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