Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.953
Filtrar
1.
Forensic Sci Int ; 306: 110066, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765884

RESUMO

In forensic evaluation of charred corpses, internal detrimental signs may result as more significant of those observed during external examination and is often arduous to state if a victim was exposed to fire before or after death. When the histological analysis of the remaining internal viscera is necessary, the massive destruction caused by the lesion, the charring and the coarctation of the samples don't allow to give further information or to determine the remaining organic components of the viscera. This limit is determined by the intrinsic characteristics of this thermal lesivity of self-maintenance even after the exitus of the subject, worsening the initial detrimental framework. The Authors, with the purpose of improving the microscopic visualization of the samples collected from cadavers with peculiar deterioration, as in case of carbonization, suggest the use of a specific technical protocol based on the use of Sandison's rehydrating solution since the samples treated with this solution showed, at microscopic examination, a substantial histological-morphological improvement.


Assuntos
Fogo , Patologia Legal/métodos , Soluções para Reidratação , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/patologia , Encéfalo/patologia , Cadáver , Dura-Máter/patologia , Esôfago/patologia , Feminino , Humanos , Intestino Delgado/patologia , Rim/patologia , Fígado/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pele/patologia , Baço/patologia , Adulto Jovem
2.
Life Sci ; 241: 117144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31830482

RESUMO

BACKGROUND: As an inflammation-related cytokine, interleukin (IL)-5 has been reported to be involved in the development of cardiovascular diseases, such as chronic heart failure and atherosclerosis. However, the role of IL-5 in acute aortic dissection (AAD) has barely been explored. METHODS: Aortic tissue samples from normal donors and patients with AAD were collected, and the expression and localization of IL-5 in aortic tissue were analyzed. In addition, a mouse AAD model was established by administering angiotensin II (Ang II) to ß-aminopropionitrile (BAPN)-treated mice. Morphological examinations and histopathologic analyses were performed to evaluate the effects of IL-5 overexpression on the occurrence of AAD. RESULTS: IL-5 expression was significantly decreased in aorta samples from AAD patients compared to those from donors, and macrophages were the main source of IL-5. In addition, IL-5 expression was decreased in plasma and aortic tissue samples from AAD mice. IL-5 overexpression markedly attenuated the occurrence of AAD in mice and produced corresponding decreases in the inflammatory response and cell apoptosis. In cocultures of macrophages and smooth muscle cells (SMCs), IL-5 overexpression in the macrophages significantly reduced Ang II-induced SMC apoptosis. CONCLUSION: IL-5 overexpression suppresses the development of AAD by reducing inflammation and SMC apoptosis. These results suggest that IL-5 is a potential therapeutic target in AAD.


Assuntos
Aneurisma Dissecante/prevenção & controle , Apoptose , Modelos Animais de Doenças , Inflamação/prevenção & controle , Interleucina-5/metabolismo , Macrófagos/patologia , Miócitos de Músculo Liso/patologia , Aminopropionitrilo/toxicidade , Aneurisma Dissecante/induzido quimicamente , Aneurisma Dissecante/complicações , Aneurisma Dissecante/metabolismo , Angiotensina II/toxicidade , Animais , Aorta/metabolismo , Aorta/patologia , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-5/genética , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Prognóstico
4.
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
5.
Zhonghua Nei Ke Za Zhi ; 58(11): 808-813, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665855

RESUMO

Objective: Positron emission tomography-computed tomography (PET-CT) has been used to quantify inflammatory response in the body. The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques. Methods: Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group, with 10 rabbits in each group. Rabbits in both groups were fed with a high fat diet for 20 weeks, and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week. Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day. At the 8th week, thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits. Blood was drawn at the 3rd and the 20th week, respectively, to measure blood lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). At the end of experiment, survival animals were scanned by (18)F-FDG PET-CT, and the average and maximum standard uptake values (SUVmean, SUVmax) of aortic segments were measured. Thereafter, the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry. The pathological indexes were measured and compared. Results: At the end of experiment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hs-CRP [ (4.58±0.51) ng/ml vs.(5.87±0.66) ng/ml, P<0.01], MMP-9[ (43.93±2.16) ng/ml vs. (50.77±2.32) ng/ml, P<0.01], SUVmean (0.59±0.15 vs. 0.68±0.20, P<0.05) , SUVmax (0.68±0.20 vs. 0.81±0.27, P<0.05) , plaque area [ (0.36±0.24) mm(2) vs. (0.50±0.34) mm(2), P<0.05) ] and density of macrophage[ (4.34±1.54) % vs. (5.65±1.89) %, P<0.01] in the atorvastatin intervention group were significantly lower than those in the control group. In contrast, fiber cap thickness of the plaque[ (4.12±0.66) µm vs. (2.96±0.37) µm, P<0.01] in the atorvastatin intervention group was higher than that of the control group, and the difference was statistically significant. The arterial plaque areas were positively correlated with SUVmean (r=0.27, P<0.05) and SUVmax (r=0.43, P<0.01) . Fiber cap thickness was negatively correlated with SUVmean (r=-0.38, P<0.05) and SUVmax (r=-0.47, P<0.01) . The density of macrophage were positively correlated with SUVmean (r=0.52, P<0.01) and SUVmax (r=0.51, P<0.01) . Conclusion: (18)F-FDG PET/CT can be used to evaluate the efficacy of atorvastatin by the stability of atherosclerotic plaques.


Assuntos
Aorta/diagnóstico por imagem , Fluordesoxiglucose F18/administração & dosagem , Placa Aterosclerótica/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Animais , Aorta/patologia , Masculino , Placa Aterosclerótica/patologia , Coelhos , Compostos Radiofarmacêuticos
6.
Int J Nanomedicine ; 14: 7503-7513, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686818

RESUMO

Background: The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated. Research design and methods: In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography. Results: Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group. Conclusion: The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Stents Farmacológicos , Endotélio/patologia , Nanofibras/química , Neointima/tratamento farmacológico , Vildagliptina/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Colágeno Tipo I/metabolismo , Endotélio/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Masculino , Nanofibras/ultraestrutura , Coelhos , Vildagliptina/farmacologia
7.
Yonsei Med J ; 60(11): 1036-1044, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637885

RESUMO

PURPOSE: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. MATERIALS AND METHODS: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. RESULTS: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. CONCLUSION: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.


Assuntos
Tecido Adiposo/citologia , Aterosclerose/fisiopatologia , Aterosclerose/terapia , Endotélio Vascular/fisiopatologia , Inflamação/terapia , Transplante de Células-Tronco , Animais , Aorta/patologia , Aterosclerose/sangue , Citocinas/sangue , Modelos Animais de Doenças , Endotélio Vascular/patologia , Inflamação/sangue , Inflamação/patologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais
8.
Nat Genet ; 51(11): 1580-1587, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659325

RESUMO

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.


Assuntos
Aterosclerose/patologia , Predisposição Genética para Doença , Histona Desacetilases/metabolismo , Histona Desacetilases/fisiologia , Contração Muscular , Músculo Liso Vascular/patologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Calcificação Vascular/patologia , Idoso , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Estudos de Coortes , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Estudo de Associação Genômica Ampla , Histona Desacetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Calcificação Vascular/genética , Calcificação Vascular/metabolismo
9.
Zhonghua Fu Chan Ke Za Zhi ; 54(10): 660-665, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31648441

RESUMO

Objective: To analyze the pregnancy outcomes of fetal tetralogy of Fallot and to explore its prenatal diagnosis and treatment procedures. Methods: The clinical data of 63 cases of fetal tetralogy of Fallot (62 cases were singleton and 1 case was one of twin) were collected retrospectively from November, 2013 to November, 2017 in Beijing Obstetrics and Gynecology Hospital. Results: (1) Totally, 63 cases out of 46 352 pregnancies were diagnosed fetal tetralogy of Fallot by fetal ultrasonic cardiogram with about 0.136%(63/46 352) occurrence rate, and the mean gestational age was (23±3) weeks. And 50 cases (79%, 50/63) terminated pregnancy by induced labour. (2) Totally, 57 cases (90%,57/63) accepted genetic diagnosis.Eight cases (13%, 8/63) existed chromosome abnormality including 21-trimosy in 6 cases, 18-trisomy in 1 case and 22q11.2 microdeletion syndrome in 1 case; and these 8 cases were determined before 28 gestational weeks. (3) And 13 cases (21%, 13/63) of no fetal genetic abnormality selected to continue pregnancy. Twelve cases underwent full term delivery (5 cases were cesarean section delivery and 7 cases were vaginal delivery). Twelve newborns underwent surgical radical operation on heart malformation and got recovery. One case underwent preterm cesarean section at 35 gestational weeks for one of twin, and the newborn with tetralogy of Fallot was dead. The other the newborns survived and were followed up for tetralogy of Fallot surgery from 1 month to 3 years old after birth and recovered. Conclusions: Fetal tetralogy of Fallot mainly is diagnosed by ultrasonic cardiogram in the second trimester. The gestational age of diagnosis may be as early as 15 gestational weeks. Fetal tetralogy of Fallot with no genetic abnormality could underwent radical heart malformation operation after birth. It is necessary to undergo genetic testing on fetal tetralogy of Fallot and prenatal multidisciplinary counseling as well.


Assuntos
Resultado da Gravidez , Diagnóstico Pré-Natal/métodos , Tetralogia de Fallot/diagnóstico por imagem , Ultrassonografia Pré-Natal , Aorta/diagnóstico por imagem , Aorta/patologia , Cesárea , Feminino , Feto , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Tetralogia de Fallot/diagnóstico
10.
Life Sci ; 237: 116896, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605707

RESUMO

AIMS: Population-based studies have shown that exercise has anti-atherosclerotic effects, but the mechanisms underlying this cardiac protection are poorly understood. The aim of this study was to investigate if the anti-atherosclerotic effects of exercise are associated with changes in neuropeptide Y (NPY) expression in apolipoprotein E-deficient (ApoE-/-) mice. MAIN METHODS: Thirty-one male ApoE-/- mice were randomly divided into regular exercise (5 days/week), occasional exercise (1-2 days/week), and sedentary groups. After 8 weeks, atherosclerotic burden and plaque stability were measured by histological and morphological analysis. Quantitative real-time PCR and immunohistochemistry were used to measure the expression of NPY and its receptors in the aorta. KEY FINDINGS: Eight weeks of occasional exercise was equally effective as regular exercise at preventing atherosclerotic plaque formation and enhancing atherosclerotic plaque stability. This was shown by increased plaque collagen and smooth muscle cell content and decreased plaque lipid and macrophage content. The expression of NPY and its receptors in the vasculature was decreased in the regular exercise and occasional exercise groups, and this expression was significantly correlated with the progress of atherosclerosis. Moreover, exercise may reduce the activity of macrophages by down-regulating the expression of NPY Y1 receptors, thereby reducing the release of inflammatory cytokines. SIGNIFICANCE: These results suggest that exercise training can attenuate plaque burden and enhance atherosclerotic plaque stability. The anti-atherosclerotic effect of exercise appears to be, at least in part, dependent on down-regulation of the expression of NPY and its receptors (especially Y1 receptors) in the aorta.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/prevenção & controle , Regulação da Expressão Gênica , Inflamação/prevenção & controle , Neuropeptídeo Y/metabolismo , Condicionamento Físico Animal , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neuropeptídeo Y/genética
11.
Chem Biol Interact ; 314: 108842, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586451

RESUMO

BACKGROUND AND AIMS: Chronic psychosocial stress is a risk factor for cardiovascular disease. In view of the important role of dipeptidyl peptidase-4 (DPP-4) in human pathophysiology, we studied the role of DPP-4 in stress-related vascular aging in mice, focusing on oxidative stress and the inflammatory response. METHODS AND RESULTS: Male mice were randomly divided into a non-stress group and an immobilization stress group treated for 2 weeks. Chronic stress accelerates aortic senescence and increases plasma DPP-4 levels. Stress increased the levels of gp91phox, p22phox, p47phox, p67phox, p53, p27, p21, p16INK4A, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsin S (Cat S), and Cat K mRNAs and/or protein in the aorta of the stressed mice and decreased their levels of endothelial nitric oxide synthase and SirTuin1 (SirT1). DPP-4 inhibitors can improve stress-induced targeting molecules and morphological changes. In vitro, the inhibition of DPP-4 also alleviated the changes in the oxidative and inflammatory molecules in response to hydrogen peroxide in human umbilical vein endothelial cells. CONCLUSIONS: DPP-4 inhibition can improve vascular aging in stressed mice, possibly by improving oxidative stress production and vascular inflammation. Our results suggest that DPP-4 may become a new therapeutic target for chronic stress-related vascular aging in metabolic cardiovascular diseases.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Aorta/metabolismo , Aorta/patologia , Dipeptidil Peptidase 4/sangue , Dipeptidil Peptidase 4/química , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Pirimidinas/farmacologia , Sirtuína 1/metabolismo , Estresse Fisiológico
12.
Toxicol Lett ; 316: 27-34, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513887

RESUMO

OBJECTIVE: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4+CD25+Foxp3+ Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4+CD25+Foxp3+ Tregs population and atherosclerotic development in ApoE-/- mice exposed to PM2.5. METHODS: We employed a real-world system to subject 40 ApoE-/- mice to ambient inhalation of PM2.5 (PM2.5 group, n = 20) or filtered air (FA group, n = 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively. RESULTS: The daily average concentration of PM2.5 was 57.4 ± 25.6 µg/m3. Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-α, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-ß, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group. CONCLUSION: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoE-/- mice, which is related to CD4+CD25+Foxp3+ Tregs down-regulation, as well as lipid deposition and systemic inflammation.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/induzido quimicamente , Aterosclerose/induzido quimicamente , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Material Particulado/toxicidade , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Aorta/imunologia , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/imunologia , Aterosclerose/patologia , Biomarcadores/sangue , LDL-Colesterol/sangue , Citocinas/sangue , Modelos Animais de Doenças , Progressão da Doença , Fatores de Transcrição Forkhead/imunologia , Predisposição Genética para Doença , Mediadores da Inflamação/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Tamanho da Partícula , Fenótipo , Placa Aterosclerótica , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Fatores de Tempo
13.
Medicine (Baltimore) ; 98(33): e16802, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415390

RESUMO

Impact of arterial stiffness on aortic morphology has not been well evaluated. We sought to investigate the association of brachial-ankle pulse wave velocity (baPWV) with aortic calcification and tortuosity.A total of 181 patients (65.4 ±â€Š10.4 years, males 59.7%) who underwent computed tomographic angiography and baPWV measurement within 1 month of study entry were retrospectively reviewed. Aortic calcification was quantified by the calcium scoring software system. Aortic tortuosity was defined as the length of the midline in the aorta divided by the length of linear line from the aortic root to the distal end of the thoraco-abdominal aorta. In simple correlation analyses, baPWV was correlated with aortic calcification (r = 0.36, P < .001) and tortuosity (r = 0.16, P = .030). However, these significances disappeared after controlling for confounders in multivariate analyses. Factors showing an independent association with aortic calcification were age (ß = 0.37, P < .001), hypertension (ß = 0.19, P = .003), diabetes mellitus (ß = 0.12, P = .045), smoking (ß = 0.17, P = .016), and estimated glomerular filtration rate (ß = -0.25, P = .002). Factors showing an independent association with aortic tortuosity were age (ß = 0.34, P < .001), body mass index (ß = -0.19, P = .018), and diabetes mellitus (ß = -0.21, P = .003).In conclusion, baPWV reflecting arterial stiffness was not associated with aortic calcification and tortuosity. Traditional cardiovascular risk factors were more influential to aortic geometry. Further studies with a larger sample size are needed to confirm our results.


Assuntos
Aorta/patologia , Artérias/anormalidades , Instabilidade Articular/fisiopatologia , Dermatopatias Genéticas/fisiopatologia , Calcificação Vascular/fisiopatologia , Malformações Vasculares/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Índice Tornozelo-Braço , Aorta/fisiopatologia , Artérias/patologia , Artérias/fisiopatologia , Índice de Massa Corporal , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Instabilidade Articular/patologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Estudos Retrospectivos , Dermatopatias Genéticas/patologia , Calcificação Vascular/patologia , Malformações Vasculares/patologia
14.
Oxid Med Cell Longev ; 2019: 6721531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396305

RESUMO

Aims: The neutrophil recruiting cytokine Interleukin-17A (IL-17A) is a key component in vascular dysfunction and arterial hypertension. Moreover, IL-17A has a central role for the vascular infiltration of myeloid cells into the arterial wall in Angiotensin II-induced vascular inflammation. The intention of our study was to analyze the impact of T cell-derived IL-17A on hypertension, vascular function, and inflammation. Methods and Results: Chronic IL-17A overexpression in T cells (CD4-IL-17Aind/+ mice) resulted in elevated reactive oxygen species in the peripheral blood and a significant vascular dysfunction compared to control mice. The vascular dysfunction seen in the CD4-IL-17Aind/+ mice was only accompanied by a modest and nonsignificant accumulation of inflammatory cells within the vessel wall. Therefore, infiltrating myeloid cells did not serve as an explanation of the vascular dysfunction seen in a chronic IL-17A-driven mouse model. In addition to vascular dysfunction, CD4-IL-17Aind/+ mice displayed vascular fibrosis with highly proliferative fibroblasts. This fibroblast proliferation was induced by exposure to IL-17A as confirmed by in vitro experiments with primary murine fibroblastic cells. We also found that the ·NO/cGMP pathway was downregulated in the vasculature of the CD4-IL-17Aind/+ mice, while levels of protein tyrosine kinase 2 (PYK2), an oxidative stress-triggered process associated with T cell activation, were upregulated in the perivascular fat tissue (PVAT). Conclusions: Our data demonstrate that T cell-derived IL-17A elicits vascular dysfunction by mediating proliferation of fibroblasts and subsequent vascular fibrosis associated with PYK2 upregulation.


Assuntos
GMP Cíclico/metabolismo , Endotélio Vascular/fisiopatologia , Interleucina-17/metabolismo , Óxido Nítrico/metabolismo , Linfócitos T/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Proliferação de Células , Regulação para Baixo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibrose , Quinase 2 de Adesão Focal/metabolismo , Interleucina-17/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Subunidades Proteicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Guanilil Ciclase Solúvel/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Regulação para Cima
15.
J Med Food ; 22(10): 1000-1008, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31460816

RESUMO

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/sangue , Lactoferrina/farmacologia , Animais , Aorta/patologia , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol na Dieta/administração & dosagem , Dieta Hiperlipídica , Fígado Gorduroso/fisiopatologia , Homeostase , Intestino Delgado/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE
16.
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
17.
Mol Cell Biochem ; 462(1-2): 61-73, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446617

RESUMO

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE-/-) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE-/- mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE-/- mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE-/- mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/genética , Perfilação da Expressão Gênica , RNA Longo não Codificante/genética , Animais , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/metabolismo , Análise por Conglomerados , Ontologia Genética , Redes Reguladoras de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
Kidney Blood Press Res ; 44(4): 823-834, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266041

RESUMO

BACKGROUND/AIMS: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. MATERIALS: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. RESULTS: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). CONCLUSION: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.


Assuntos
Aorta/patologia , Progressão da Doença , Hipercalcemia/complicações , Transplante de Rim/efeitos adversos , Calcificação Vascular/etiologia , Adulto , Aorta/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Rigidez Vascular
19.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269711

RESUMO

Bicuspid aortic valve (BAV), the most common congenital heart defect, is associated with an increased prevalence of aortic dilation, aortic rupture and aortic valve calcification. Endothelial cells (ECs) play a major role in vessel wall integrity. Little is known regarding EC function in BAV patients due to lack of patient derived primary ECs. Endothelial colony forming cells (ECFCs) have been reported to be a valid surrogate model for several cardiovascular pathologies, thereby facilitating an in vitro system to assess patient-specific endothelial dysfunction. Therefore, the aim of this study was to investigate cellular functions in ECFCs isolated from BAV patients. Outgrowth and proliferation of ECFCs from patients with BAV (n = 34) and controls with a tricuspid aortic valve (TAV, n = 10) were determined and related to patient characteristics. Interestingly, we were only able to generate ECFCs from TAV and BAV patients without aortic dilation, and failed to isolate ECFC colonies from patients with a dilated aorta. Analyzing EC function showed that while proliferation, cell size and endothelial-to-mesenchymal transition were similar in TAV and BAV ECFCs, migration and the wound healing capacity of BAV ECFCs is significantly higher compared to TAV ECFCs. Furthermore, calcification is blunted in BAV compared to TAV ECFCs. Our results reveal ECs dysfunction in BAV patients and future research is required to unravel the underlying mechanisms and to further validate ECFCs as a patient-specific in vitro model for BAV.


Assuntos
Valva Aórtica/anormalidades , Células Endoteliais/patologia , Doenças das Valvas Cardíacas/patologia , Adulto , Aorta/patologia , Valva Aórtica/patologia , Movimento Celular , Tamanho Celular , Células Cultivadas , Dilatação Patológica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289149

RESUMO

Acute aortic dissection presenting neurological symptoms is rare and entails significant diagnostic challenges. We present a case of 45-year-old woman with a medical history of essential hypertension and smoking, admitted with lobar pneumonia. During her inpatient treatment, she developed severe back pain and numbness below the level of the umbilicus. Due to her presenting symptoms considered differential diagnoses were paravertebral abscess and acute stroke. CT scan of the head did not reveal any ischaemic changes. Further investigation with MRI (with and without contrast) raised concerns for possible aortic dissection. CT angiography of thorax, abdomen and pelvis displayed extensive aortic dissection extending from aortic root to left iliac artery limiting flow to right carotid artery causing stenosis. The patient was diagnosed with Stanford type A aortic dissection. The patient was referred to the cardiothoracic surgery team for surgical repair. The patient made a good recovery after a prolonged course of hospitalisation, followed by cardiac rehabilitation and physical therapy.


Assuntos
Aneurisma Dissecante/complicações , Aneurisma Dissecante/cirurgia , Paraplegia/etiologia , Doença Aguda , Aneurisma Dissecante/classificação , Aneurisma Dissecante/patologia , Aorta/diagnóstico por imagem , Aorta/patologia , Artérias Carótidas/patologia , Angiografia por Tomografia Computadorizada/métodos , Constrição Patológica , Diagnóstico Diferencial , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/patologia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Paraplegia/fisiopatologia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA