Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.861
Filtrar
1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
Ann Thorac Cardiovasc Surg ; 25(5): 265-273, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31378750

RESUMO

PURPOSE: Our study aimed to investigate the potential pathogenetic theories of different phenotype prevalence in bicuspid aortopathy. METHODS: A total of 407 bicuspid aortic valve (BAV) patients with aortic dilation were retrospectively reviewed. Association was determined between aortic valve lesion types and aortic configurations to confirm the homogeneous BAV subsets, and then, dominance analysis was used to evaluate the relative importance of two components of aortic valve lesion (BAV phenotype and valvular dysfunction) that associated with aortic configurations in each subgroup. RESULTS: Dominance analysis showed that Type-1 LR was the dominant contributor (79.0% and 79.6%) associated with the higher prevalence of the dilation of aortic root (AoR) and ascending aorta (AAo) in BAV patients with Type-1 LR and aortic regurgitation (AR) or aortic stenosis (AS) + AR. However, AS was the main contributor (60.0%) associated with the raised incidence of the dilation of AAo and proximal aortic arch (PArc) in Type-0 LAT and AS. CONCLUSIONS: Different dominant pathogenetic theory determined the phenotype of BAV aortopathy. In patients of Type-1 LR with AR, inherent disposition is mainly responsible for the higher frequency of AoR dilation. Valve-related hemodynamics determined greater prevalence of the dilation of AAo and PArc in patients of Type-0 LAT with AS.


Assuntos
Aneurisma Aórtico/epidemiologia , Insuficiência da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/epidemiologia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/epidemiologia , Adulto , Idoso , Aorta/diagnóstico por imagem , Aorta/patologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Pequim/epidemiologia , Dilatação Patológica , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Estudos Retrospectivos
9.
Forensic Sci Med Pathol ; 15(4): 591-594, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446611

RESUMO

The body of a 43-year-old African woman with a history of aortic aneurysm and hypertension was forensically investigated after her sudden death. The cause of death was related to a cardiac tamponade due to a ruptured aneurysm of the ascending aorta. Post-mortem gross examination showed an abnormal whitish discoloration of the intima with fibrous thickening of the aortic wall. Several arteries (left main and circumflex coronaries, carotid, renal and iliac arteries) showed similar features. Upon histological examination, the aortic aneurysm as well as the other arteries sampled showed mucoid degeneration, excess mucopolysaccharides and pools of mucin inside the intima and the media associated with collagen and elastic fiber destruction and loss of smooth muscle cells. This pattern strongly suggested the diagnosis of intimomedial mucoid degeneration (IMMD), a rare arterial disorder consisting of a progressive deposition of mucin into the intima and media, with a strong prevalence in middle-aged black African females with high blood pressure. In addition to the typical features of IMMD, histological examination of the ascending aorta showed a thickening of the adventita with sparse mixed inflammatory infiltrates and fibrosis, suggesting an additional chronic infectious aortitis. No infectious agent was detected. The body of literature on IMMD is reviewed and the origin of death is discussed in this case report.


Assuntos
Aorta/patologia , Aneurisma Aórtico/patologia , Glicosaminoglicanos/metabolismo , Mucinas/metabolismo , Túnica Íntima/patologia , Túnica Média/patologia , Adulto , Túnica Adventícia/patologia , Grupo com Ancestrais do Continente Africano , Vasos Coronários/patologia , Morte Súbita/etiologia , Feminino , Fibrose/patologia , Patologia Legal , Humanos , Hipertensão/complicações , Túnica Íntima/metabolismo , Túnica Média/metabolismo
10.
Biomed Res Int ; 2019: 9104680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31263710

RESUMO

Background: The pathogenesis of abdominal aortic aneurysm (AAA) is characterized by atherosclerosis with chronic inflammation in the aortic wall. Montelukast is a selective cys-LT 1 receptor antagonist that can suppress atherosclerotic diseases. We evaluated the in vitro properties of montelukast and its in vivo activities in an angiotensin II-infused apolipoprotein E-deficient (apoE-/-) AAA mouse model. Methods: The mouse monocyte/macrophage cell line J774A.1 was used in vitro. M1 macrophages were treated with montelukast, and gene expressions of inflammatory cytokines were measured. Macrophages were cultured with montelukast, then gene expressions of arginase-1 and IL (interleukin)-10 were assessed by quantitative polymerase chain reaction, arginase-1 was measured by fluorescence-activated cell sorting, and IL-10 concentration was analyzed by enzyme-linked immunosorbent assay. In vivo, one group (Mont, n=7) received oral montelukast (10 mg/kg/day) for 28 days, and the other group (Saline, n=7) was given normal Saline as a control for the same period. Aortic diameters, activities of matrix metalloproteinases (MMPs), cytokine concentrations, and the number of M2 macrophages were analyzed. Results: Relative to control, montelukast significantly suppressed gene expressions of MMP-2, MMP-9, and IL-1ß, induced gene expressions of arginase-1 and IL-10, enhanced the expression of the arginase-1 cell surface protein, and increased the protein concentration of IL-10. In vivo, montelukast significantly decreased aortic expansion (Saline vs Mont; 2.44 ± 0.15 mm vs 1.59 ± 0.20 mm, P<.01), reduced MMP-2 activity (Saline vs Mont; 1240 µM vs 755 µM, P<.05), and induced infiltration of M2 macrophages (Saline vs Mont; 7.51 % vs 14.7 %, P<.05). Conclusion: Montelukast induces M2 macrophage polarization and prevents AAA formation in apoE-/- mice.


Assuntos
Acetatos/uso terapêutico , Aneurisma Aórtico/tratamento farmacológico , Polaridade Celular , Macrófagos/metabolismo , Quinolinas/uso terapêutico , Receptores de Leucotrienos/metabolismo , Acetatos/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/enzimologia , Aorta/patologia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/patologia , Arginase/genética , Arginase/metabolismo , Linhagem Celular , Polaridade Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Macrófagos/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Quinolinas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
11.
Clin Sci (Lond) ; 133(13): 1439-1455, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31235554

RESUMO

The long non-coding RNA (lncRNA) PTENP1 is a pseudogene of phosphatase and tensin homologue deleted on chromosome ten (PTEN), has been implicated in smooth muscle cell (SMC) proliferation and apoptosis. PTENP1 is the pseudogene of PTEN. However, it is unclear whether and how PTENP1 functions in the proliferation and apoptosis of human aortic SMCs (HASMCs). Here, we hypothesised that PTENP1 inhibits HASMC proliferation and enhances apoptosis by promoting PTEN expression. PCR analysis and Western blot assays respectively showed that both PTENP1 and PTEN were up-regulated in human aortic dissection (AD) samples. PTENP1 overexpression significantly increased the protein expression of PTEN, promoted apoptosis and inhibited the proliferation of HASMCs. PTENP1 silencing exhibited the opposite effects and mitigated H2O2-induced apoptosis of HASMCs. In an angiotensin II (Ang II)-induced mouse aortic aneurysm (AA) model, PTENP1 overexpression potentiated aortic SMC apoptosis, exacerbated aneurysm formation. Mechanistically, RNA pull-down assay and a series of luciferase reporter assays using miR-21 mimics or inhibitors identified PTENP1 as a molecular sponge for miR-21 to endogenously compete for the binding between miR-21 and the PTEN transcript, releasing PTEN expression. This finding was further supported by in vitro immunofluorescent evidence showing decreased cell apoptosis upon miR-21 mimic administration under baseline PTENP1 overexpression. Ex vivo rescue of PTEN significantly mitigated the SMC apoptosis induced by PTENP1 overexpression. Finally, Western blot assays showed substantially reduced Akt phosphorylation and cyclin D1 and cyclin E levels with up-regulated PTENP1 in HASMCs. Our study identified PTENP1 as a mediator of HASMC homeostasis and suggests that PTENP1 is a potential target in AD or AA intervention.


Assuntos
Aneurisma Dissecante/metabolismo , Aneurisma Aórtico/metabolismo , Apoptose , Proliferação de Células , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Pseudogenes , RNA Longo não Codificante/metabolismo , Aneurisma Dissecante/genética , Aneurisma Dissecante/patologia , Animais , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Ciclo Celular , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
12.
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
13.
Int Heart J ; 60(3): 688-694, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105154

RESUMO

The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.


Assuntos
Aneurisma Aórtico/imunologia , Estenose da Valva Aórtica/imunologia , Doença Relacionada a Imunoglobulina G4/sangue , Imunoglobulina G/sangue , Plasmócitos/patologia , Idoso , Idoso de 80 Anos ou mais , Aorta/anatomia & histologia , Aorta/citologia , Aorta/diagnóstico por imagem , Aorta/cirurgia , Aneurisma Aórtico/sangue , Aneurisma Aórtico/patologia , Valva Aórtica/citologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/patologia , Ecocardiografia/métodos , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Período Pré-Operatório , Estudos Retrospectivos
15.
Am J Physiol Cell Physiol ; 317(2): C262-C269, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116584

RESUMO

Phenotypic transformation of vascular smooth muscle cells is a key phenomenon in the development of aortic dissection disease. However, the molecular mechanisms underlying this phenomenon have not been fully understood. We used ß-BAPN combined with ANG II treatment to establish a disease model of acute aortic dissection (AAD) in mice. We first examined the gene expression profile of aortic tissue in mice with AAD using a gene chip, followed by confirmation of DExH-box helicase 9 (DHX9) expression using RT-PCR, Western blot, and immunofluorescence analysis. We further developed vascular smooth muscle cell-specific DHX9 conditional knockout mice and conducted differential and functional analysis of gene expression and alternative splicing in mouse vascular smooth muscle cells. Finally, we examined the involvement of DHX9 in Krüppel-like factor 5 (KLF5) mRNA alternative splicing. Our study reported a significant decrease in the expression of DHX9 in the vascular smooth muscle cells (VSMCs) of mice with AAD. The smooth muscle cell-specific knockout of DHX9 exacerbated the development of AAD and altered the transcriptional level expression of many smooth muscle cell phenotype-related genes. Finally, we reported that DHX9 may induce alternative splicing of KLF5 mRNA by bridging YB-1. These results together suggested a new pathogenic mechanism underlying the development of AAD, and future research of this mechanism may help identify effective therapeutic intervention for AAD.


Assuntos
Processamento Alternativo , Aneurisma Dissecante/enzimologia , Aneurisma Aórtico/enzimologia , Plasticidade Celular , RNA Helicases DEAD-box/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Aneurisma Dissecante/genética , Aneurisma Dissecante/patologia , Animais , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Células Cultivadas , RNA Helicases DEAD-box/genética , Modelos Animais de Doenças , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos Endogâmicos C57BL , Complexos Multiproteicos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fenótipo , RNA Mensageiro/genética , Transdução de Sinais , Fatores de Transcrição/genética
16.
EBioMedicine ; 43: 54-66, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31078518

RESUMO

BACKGROUND: Ascending aortic aneurysms constitute an important hazard for individuals with a bicuspid aortic valve (BAV). However, the processes that degrade the aortic wall in BAV disease remain poorly understood. METHODS: We undertook in situ analysis of ascending aortas from 68 patients, seeking potentially damaging cellular senescence cascades. Aortas were assessed for senescence-associated-ß-galactosidase activity, p16Ink4a and p21 expression, and double-strand DNA breaks. The senescence-associated secretory phenotype (SASP) of cultured-aged BAV aortic smooth muscle cells (SMCs) was evaluated by transcript profiling and consequences probed by combined immunofluorescence and circular polarization microscopy. The contribution of p38 MAPK signaling was assessed by immunostaining and blocking strategies. FINDINGS: We uncovered SMCs at varying depths of cellular senescence within BAV- and tricuspid aortic valve (TAV)-associated aortic aneurysms. Senescent SMCs were also abundant in non-aneurysmal BAV aortas but not in non-aneurysmal TAV aortas. Multivariable analysis revealed that BAV disease independently associated with SMC senescence. Furthermore, SMC senescence was heightened at the convexity of aortas associated with right-left coronary cusp fusion. Aged BAV SMCs had a pronounced collagenolytic SASP. Moreover, senescent SMCs in the aortic wall were enriched with surface-localized MMP1 and surrounded by weakly birefringent collagen fibrils. The senescent-collagenolytic SMC phenotype depended on p38 MAPK signaling, which was chronically activated in BAV aortas. INTERPRETATION: We have identified a cellular senescence-collagen destruction axis in at-risk ascending aortas. This novel "seno-destructive" SMC phenotype could open new opportunities for managing BAV aortopathy. FUND: Canadian Institutes of Health Research, Lawson Health Research Institute, Heart and Stroke Foundation of Ontario/Barnett-Ivey Chair.


Assuntos
Aorta/metabolismo , Aorta/patologia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/patologia , Miócitos de Músculo Liso/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Valva Aórtica/patologia , Biomarcadores , Células Cultivadas , Senescência Celular , Colágeno/metabolismo , Quebras de DNA de Cadeia Dupla , Feminino , Doenças das Valvas Cardíacas/complicações , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Proteólise , Fatores de Risco
17.
Arterioscler Thromb Vasc Biol ; 39(6): 1149-1159, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30943775

RESUMO

Objective- Recent studies suggested the occurrence of phenotypic switching of vascular smooth muscle cells (VSMCs) during the development of aortic aneurysm (AA). However, lineage-tracing studies are still lacking, and the behavior of VSMCs during the formation of dissecting AA is poorly understood. Approach and Results- We used multicolor lineage tracing of VSMCs to track their fate after injury in murine models of Ang II (angiotensin II)-induced dissecting AA. We also addressed the direct impact of autophagy on the response of VSMCs to AA dissection. Finally, we studied the relevance of these processes to human AAs. Here, we show that a subset of medial VSMCs undergoes clonal expansion and that VSMC outgrowths are observed in the adventitia and borders of the false channel during Ang II-induced development of dissecting AA. The clonally expanded VSMCs undergo phenotypic switching with downregulation of VSMC differentiation markers and upregulation of phagocytic markers, indicative of functional changes. In particular, autophagy and endoplasmic reticulum stress responses are activated in the injured VSMCs. Loss of autophagy in VSMCs through deletion of autophagy protein 5 gene ( Atg5) increases the susceptibility of VSMCs to death, enhances endoplasmic reticulum stress activation, and promotes IRE (inositol-requiring enzyme) 1α-dependent VSMC inflammation. These alterations culminate in increased severity of aortic disease and higher incidence of fatal AA dissection in mice with VSMC-restricted deletion of Atg5. We also report increased expression of autophagy and endoplasmic reticulum stress markers in VSMCs of human dissecting AAs. Conclusions- VSMCs undergo clonal expansion and phenotypic switching in Ang II-induced dissecting AAs in mice. We also identify a critical role for autophagy in regulating VSMC death and endoplasmic reticulum stress-dependent inflammation with important consequences for aortic wall homeostasis and repair.


Assuntos
Aneurisma Dissecante/patologia , Aneurisma Aórtico/patologia , Autofagia , Plasticidade Celular , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Adulto , Idoso , Aneurisma Dissecante/induzido quimicamente , Aneurisma Dissecante/metabolismo , Angiotensina II , Animais , Aorta/metabolismo , Aorta/patologia , Aneurisma Aórtico/induzido quimicamente , Aneurisma Aórtico/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem da Célula , Células Cultivadas , Modelos Animais de Doenças , Endorribonucleases/metabolismo , Feminino , Humanos , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
18.
PLoS One ; 14(3): e0213794, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30883576

RESUMO

Pathological impairment of elastic fiber and other extracellular matrix (ECM) components are described for the aortic media of ascending thoracic aortic aneurysms (aTAA) but the exact pathological impairment of the structure and its degree still needs further investigations. To evaluate the quantity and quality of elastic fiber sheets and other ECM structures (e.g. collagen), cells were removed from different types of aneurysmal tissues (tricuspid aortic valve [TAV] associated-, bicuspid aortic valve [BAV] associated-aneurysmal tissue and acute aortic dissections [AAD]) using 2.5% sodium hydroxide (NaOH) and compared to decellularized control aortic tissue. Likewise, native tissue has been analysed. To evaluate the 2D- (histological evaluation, fluorescence- and auto-fluorescence based staining methods) and the 3D structure (scanning electron microscopic [SEM] examination) of the medial layer we first analysed for a successful decellularization. After proving for successful decellularization, we quantified the amount of elastic fiber sheets, elastin and other ECM components including collagen. Aside from clearly visible focal elastic fiber loss in TAV-aTAA tissue, decellularization resulted in reduction of elastic fiber auto-fluorescence properties, which is perhaps an indication from a disease-related qualitative impairment of elastic fibers, visible only after contact with the alkaline solution. Likewise, the loss of collagen amount in BAV-aTAA and TAV-aTAA tissue (compared to non-decellularized tissue) after contact with NaOH indicates a prior disease-associated impairment of collagen. Although the amount of ECM was not changed in type A dissection tissue, detailed electron microscopic evaluation revealed changes in ECM quality, which worsened after contact with alkaline solution but were not visible after histological analyses. Apart from the improved observation of the samples using electron microscopy, contact of aneurysmal and dissected tissue with the alkaline decellularization solution revealed potential disease related changes in ECM quality which can partly be connected to already published data, but have to be proven by further studies.


Assuntos
Aneurisma Dissecante/patologia , Aneurisma Aórtico/patologia , Matriz Extracelular/ultraestrutura , Microscopia Eletrônica de Varredura/métodos , Tecidos Suporte , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
PLoS One ; 14(2): e0212859, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30794673

RESUMO

OBJECTIVES: Elevated matrix metalloproteinase-2 (MMP-2) tissue levels have been associated with ascending thoracic aortic aneurysm (aTAA). As MMP-2 activation is controlled by interactions among matrix metalloproteinase-14 (MMP-14), a tissue inhibitor of metalloproteinases-2 (TIMP-2) and Pro-MMP-2 in cell culture, this activation process might also play a role in aTAA. METHODS: Via gelatin zymography we analyzed tissue levels of MMP-2 isoforms (Pro-MMP-2, active MMP-2, total MMP-2) and via enzyme-linked immunosorbent assay (ELISA,) MMP-14,TIMP-2 and total MMP-2 tissue levels in N = 42 patients with aTAA. As controls, MMP-14 and TIMP-2 aortic tissue levels in N = 9 patients undergoing coronary artery bypass surgery were measured via ELISA, and levels of MMP-2 isoforms in N = 11 patients via gelatin zymography. RESULTS: Active MMP-2 was significantly higher in aTAA than in controls. Patients with aTAA exhibited significantly lower Pro-MMP-2 and TIMP-2 levels. Total MMP-2 and MMP-14 did not differ significantly between groups. Regression analysis revealed a linear relationship between TIMP-2 and the MMP-14/TIMP-2 ratio, as well as active MMP-2 in aTAA. Aneurysmatic tissue can be accurately distinguished from control aortic tissue (AUC = 1) by analyzing the active MMP-2/Pro-MMP-2 ratio with a cutoff value of 0.11, whereas MMP-14 and TIMP-2 roles are negligible in ROC analysis. CONCLUSION: A larger amount of MMP-2 is activated in aTAA than in control aortic tissue-a factor that seems to be a central process in aneurysm development. When active MMP-2 exceeds 10% compared to Pro-MMP-2, we conclude that it originates from aneurysmatic tissue, which we regard as a starting point for further studies of aTAA biomarkers. The tissue's MMP-14/TIMP-2 ratio may regulate the degree of Pro-MMP-2 activation as a determining factor, while the enzymatic activities of MMP-14 and TIMP-2 do not seem to play a key role in aneurysm development.


Assuntos
Aorta/metabolismo , Aneurisma Aórtico/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Idoso , Aorta/patologia , Aneurisma Aórtico/patologia , Biomarcadores/metabolismo , Precursores Enzimáticos/metabolismo , Feminino , Gelatinases/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA