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1.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652665

RESUMO

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1ß, IL-6, HIF-1α, TGF-ß, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.


Assuntos
Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Metildopa/farmacologia , Doenças Vasculares/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas In Vitro , Inflamação/genética , Inflamação/patologia , Placenta/efeitos dos fármacos , Placenta/patologia , Fator de Crescimento Placentário/genética , Gravidez , Trofoblastos/efeitos dos fármacos , Doenças Vasculares/genética , Doenças Vasculares/patologia
2.
Life Sci ; 276: 119402, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33785335

RESUMO

In our previous study, we observed that donor pulmonary intravascular nonclassical monocytes play a major role in early PGF, but the specific mechanism remained unclear. In this study, we investigated the mechanistic role of monocytes in inducing pyroptosis of human pulmonary microvascular endothelial cells (HPMECs) during IRI. A murine hilar ligation model of IRI was utilized whereby left lungs underwent 1 h of ischemia and 23 h of reperfusion. Monocyte depletion by intraperitoneal clodronate-liposome treatment on pulmonary edema and pyroptosis activation were determined. In vitro experiments, we performed the co-culture experiments under hypoxia-reoxygenation (H/R) conditions to mimic the IRI environment. We monitored the expression of NLRP3, caspase-1 and IL-1ß in co-cultures of monocytes (U937 cells) and HPMECs under H/R conditions. NLRP3, IL-1ß and IL-1R siRNA knockdown, caspase-1 and NF-κB pathway inhibitors were employed to elucidate the mechanism modulating HPMEC pyroptosis during H/R. Treatment of mice with clodronate-liposome attenuated IR-induced pulmonary edema, cytokine production and pyroptosis activation. In vitro, NLRP3 knockdown in monocytes reduced caspase-1 and IL-1ß secretion in co-cultures of monocytes and HPMECs. Reduced HPMEC pyroptosis was also observed either containing HPMECs with genetically engineered IL-1R knockdown or in co-culture treated with a Triplotide inhibitor that disrupts NF-κB signaling. Monocytes play a vital role in the development of transplant-associated ischemia-reperfusion injury. A potential role is that monocytes secrete IL-1ß to induce HPMEC pyroptosis via the IL-1R/NF-κB/NLRP3 pathway.


Assuntos
Endotélio Vascular/patologia , Inflamação/patologia , Pneumopatias/complicações , Monócitos/patologia , Piroptose , Traumatismo por Reperfusão/complicações , Doenças Vasculares/patologia , Animais , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamassomos , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/metabolismo , Transdução de Sinais , Células U937 , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo
3.
Viruses ; 13(2)2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567734

RESUMO

Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the ß-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.


Assuntos
Doenças Autoimunes/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/virologia , Autoimunidade , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Humanos , Hospedeiro Imunocomprometido , Inflamação , Doenças Vasculares/patologia
4.
Medicine (Baltimore) ; 100(6): e24570, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578554

RESUMO

RATIONALE: Intravenous pyogenic granuloma (IVPG) is a special type of pyogenic granuloma, and its preoperative diagnosis is difficult. We report a rare case of IVPG that develops in the lumen of the internal jugular vein (IJV). Here, we analyze the imaging characteristics of present case and summarize the imaging characteristics of previous reported cases. PATIENT CONCERNS: A 44-year-old man who presented with a growth in the IJV without any symptoms. DIAGNOSES: A diagnosis of IVPG was made, based on the pathological examination after surgery. INTERVENTIONS: The patient underwent surgery to excise the vein segment containing the neoplasm. OUTCOMES: The patient did not present with any complications in the postoperative follow-up period. LESSONS: For clinician, IVPG's preoperative diagnosis is difficult. Although histopathology remains the gold standard for diagnosis, the combination of multiple types of imaging examinations is necessary to rule out the differential diagnoses of IVPG.


Assuntos
Granuloma Piogênico/diagnóstico por imagem , Veias Jugulares/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Adulto , Granuloma Piogênico/patologia , Granuloma Piogênico/cirurgia , Humanos , Veias Jugulares/patologia , Veias Jugulares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Ultrassonografia , Doenças Vasculares/patologia , Doenças Vasculares/cirurgia
5.
Eur J Vasc Endovasc Surg ; 61(4): 664-674, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33573912

RESUMO

OBJECTIVE: A significant proportion of vascular surgery patients may have undiagnosed cognitive impairment; however, its true prevalence and impact on outcomes are unknown. The aim of this review was to estimate the prevalence of cognitive impairment among individuals with clinically significant vascular surgical pathology and investigate its associations with post-operative outcomes in those undergoing vascular surgery. METHODS: MEDLINE, EMBASE, EMCare, CINAHL, PsycINFO, and Scopus were searched for relevant studies. Included studies assessed cognitive function among individuals with either symptomatic vascular surgical pathology, or disease above threshold for intervention, using a validated cognitive assessment tool. The primary outcome measure was prevalence of cognitive impairment. Secondary outcomes included incidence of post-operative delirium (POD). Two reviewers independently extracted relevant study data and assessed risk of bias (ROBINS-E or RoB 2 tool). Prevalence (%) of cognitive impairment was calculated for individual studies and presented with 95% confidence intervals (CI). Prevalence data from comparable studies were pooled using the Mantel-Haenszel method (random effects model) for separate vascular disease types. Certainty of effect estimates was assessed using the GRADE criteria. RESULTS: Twenty-four studies (2 564 participants) were included in the systematic review, and nine studies (1 310 participants) were included in the meta-analyses. The prevalence of cognitive impairment was 61% (95% CI 48 - 74; 391 participants; low certainty) in studies including multiple vascular surgical pathologies, 38% (95% CI 32 - 44; 278 participants; very low certainty) in carotid artery disease, and 19% (95% CI 10 - 33; 641 participants; low certainty) in those with intermittent claudication. Lower cognitive assessment scores were associated with POD (five studies; 841 participants), but data were not suitable for pooling. CONCLUSION: Screening elective vascular surgery patients for cognitive impairment may be appropriate given its high prevalence, and the association of worse cognition with POD, among individuals with clinically significant vascular surgical pathology.


Assuntos
Cognição , Disfunção Cognitiva/epidemiologia , Complicações Cognitivas Pós-Operatórias/epidemiologia , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Comorbidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/psicologia , Prevalência , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia
6.
Am J Pathol ; 191(5): 947-964, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33640319

RESUMO

This study investigated the effects of long-term NF-κB inhibition in mitigating retinal vasculopathy in a type 1 diabetic mouse model (Akita, Ins2Akita). Akita and wild-type (C57BL/6J) male mice, 24 to 26 weeks old, were treated with or without a selective inhibitor of NF-κB, 4-methyl-N1-(3-phenyl-propyl) benzene-1,2-diamine (JSH-23), for 4 weeks. Treatment was given when the mice were at least 24 weeks old. Metabolic parameters, key inflammatory mediators, blood-retinal barrier junction molecules, retinal structure, and function were measured. JSH-23 significantly lowered basal glucose levels and intraocular pressure in Akita. It also mitigated vascular remodeling and microaneurysms significantly. Optical coherence tomography of untreated Akita showed thinning of retinal layers; however, treatment with JSH-23 could prevent it. Electroretinogram demonstrated that A- and B-waves in Akita were significantly smaller than in wild type mice, indicating that JSH-23 intervention prevented loss of retinal function. Protein levels and gene expression of key inflammatory mediators, such as NOD-like receptor family pyrin domain-containing 3, intercellular adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2, were decreased after JSH-23 treatment. At the same time, connexin-43 and occludin were maintained. Vision-guided behavior also improved significantly. The results show that reducing inflammation could protect the diabetic retina and its vasculature. Findings appear to have broader implications in treating not only ocular conditions but also other vasculopathies.


Assuntos
Diabetes Mellitus Experimental/complicações , Inflamação/patologia , NF-kappa B/antagonistas & inibidores , Fenilenodiaminas/farmacologia , Doenças Retinianas/prevenção & controle , Doenças Vasculares/prevenção & controle , Animais , Apoptose , Glicemia/análise , Modelos Animais de Doenças , Eletrorretinografia , Humanos , Hiperglicemia/patologia , Leucócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , NF-kappa B/metabolismo , Retina/diagnóstico por imagem , Retina/patologia , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/etiologia , Doenças Retinianas/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Doenças Vasculares/patologia
7.
BMJ Case Rep ; 14(1)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452070

RESUMO

A 65-year-old man, a smoker, presented to the emergency department with progressive digital ischaemia, fever and weight loss. The clinical examination revealed generalised lymphadenopathy and ischaemic changes of the right distal phalanges of the second, third and fourth fingers. He had an ultrasound-guided biopsy of the cervical lymph node, which showed histopathological findings of classic Hodgkin's lymphoma. Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon and seen more in solid malignancies. There are very few reported cases of PAVS in haematological malignancies, including Hodgkin's lymphoma. This case highlights the idea that the presence of acral vascular syndrome-especially in older patients-should alert physicians to search for an underlying malignancy as part of the medical evaluation. Also, it shows that medical treatment may slow the progress of the digital ischaemia until the culprit tumour has been identified and treated.


Assuntos
Doença de Hodgkin/complicações , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/patologia , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Idoso , Dedos/irrigação sanguínea , Doença de Hodgkin/diagnóstico , Humanos , Masculino
8.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431452

RESUMO

Lobular capillary haemangioma, also known as pyogenic granuloma, is a benign vascular tumour that usually originates in the skin and mucosal membrane. It sometimes derives from the lumen of a vein and the clinical presentations are various and non-specific. A 72-year-old woman complained of a sensation of pressure in her left neck for 1 month when cooking. Her left cephalic vein was enlarged with no signs of oedema, and cervical ultrasound revealed a space-occupying lesion in the left subclavian vein. Contrast-enhanced CT and MRI revealed an intravascular tumour. This tumour was removed with operation, and histopathological examination revealed intravascular capillary haemangioma. Intravascular lobular capillary haemangioma is a rare condition that occurs in the veins of the neck and upper extremities. Intravascular tumours could cause a unique symptom, such as neck discomfort associated with neck anteflexion.


Assuntos
Granuloma Piogênico/diagnóstico , Pescoço/irrigação sanguínea , Veia Subclávia/patologia , Doenças Vasculares/diagnóstico , Idoso , Implante de Prótese Vascular , Diagnóstico Diferencial , Feminino , Granuloma Piogênico/complicações , Granuloma Piogênico/patologia , Granuloma Piogênico/cirurgia , Humanos , Leiomiossarcoma/diagnóstico , Imageamento por Ressonância Magnética , Pescoço/diagnóstico por imagem , Veia Subclávia/diagnóstico por imagem , Veia Subclávia/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia , Doenças Vasculares/complicações , Doenças Vasculares/patologia , Doenças Vasculares/cirurgia , Neoplasias Vasculares/diagnóstico
9.
Clin Nucl Med ; 46(4): 335-336, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492855

RESUMO

ABSTRACT: We describe functional and anatomical imaging findings in an 86-year-old woman who was treated for paroxysmal atrial fibrillation 5 years ago with radiofrequency ablation. She had been symptom-free for 4 years. Five years after the ablation, she presented with exertional dyspnea of several months' duration. She had left bundle branch block and aortic insufficiency with normal ejection fraction on 2-dimensional echocardiogram, none of which explained her symptoms. A CT coronary angiogram showed no obstructive coronary artery disease: Coronary Artery Disease Reporting and Data System category 1. Complete occlusion of the left superior pulmonary vein was, however, noted at its origin. Lung perfusion scintigraphy was obtained to evaluate differential perfusion.


Assuntos
Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Imagem de Perfusão , Veias Pulmonares/diagnóstico por imagem , Ablação por Radiofrequência , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/cirurgia , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Humanos , Pulmão/fisiopatologia , Veias Pulmonares/cirurgia , Resultado do Tratamento , Doenças Vasculares/patologia
10.
Actas dermo-sifiliogr. (Ed. impr.) ; 112(1): 1-13, ene. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-200038

RESUMO

La patplogía vascular oclusiva es causante de diversas y variadas manifestaciones clínicas, algunas de las cuales son de catastróficas consecuencias para el paciente. Sin embargo, las causas de tal oclusión son muy variadas, extendiéndose desde trombos por acción descontrolada de los mecanismos de coagulación, hasta anomalías de los endotelios de los vasos u oclusión por materiales extrínsecos. En una serie de dos artículos hacemos una revisión de las principales causas de oclusión vascular, resumiendo sus manifestaciones clínicas principales y los hallazgos histopatológicos fundamentales. Esta primera parte corresponde a las oclusiones vasculares que cursan con trombos


Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. The causes of vascular occlusion are also highly variable, ranging from thrombi triggered by the uncontrolled activation of coagulation mechanisms, on the one hand, to endothelial dysfunction or occlusion by material extrinsic to the coagulation system on the other. In a 2-part review, we look at the main causes of vascular occlusion and the key clinical and histopathologic findings. In this first part, we focus on vascular occlusion involving thrombi


Assuntos
Humanos , Doenças Vasculares/etiologia , Trombose Venosa/complicações , Trombose Venosa/patologia , Doenças Vasculares/patologia , Fatores de Risco
11.
Microvasc Res ; 133: 104071, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949574

RESUMO

OBJECTIVE: Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. METHODS: We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. RESULTS: We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P < .016), sludge flow (P = .001), and pericapillary edema (P < .001), while recovered patients showed a higher prevalence of enlarged capillaries (P < .001), loss of capillaries (P = .002), meandering capillaries (P < .001), and empty dermal papillae (P = .006). CONCLUSION: COVID-19 patients present microvascular abnormalities at NVC. Currently ill and recovered subjects are characterized by a different distribution of elementary capillaroscopic alterations, resembling acute and post-acute microvascular damage. Further studies are needed to assess the clinical relevance of NVC in COVID-19.


Assuntos
COVID-19/complicações , Capilares/patologia , Angioscopia Microscópica , Unhas/irrigação sanguínea , Doenças Vasculares/patologia , Idoso , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doenças Vasculares/etiologia
13.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348552

RESUMO

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott-Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients.


Assuntos
Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Diarreia/etiologia , Diarreia/patologia , Oftalmopatias Hereditárias/etiologia , Oftalmopatias Hereditárias/patologia , Hipertensão/complicações , Enteropatias/etiologia , Enteropatias/patologia , AVC Isquêmico/etiologia , AVC Isquêmico/mortalidade , Anormalidades da Pele/etiologia , Anormalidades da Pele/patologia , Vasa Vasorum/patologia , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Autopsia , Encéfalo/patologia , Isquemia Encefálica/patologia , Células Cultivadas , Endocitose/genética , Células Endoteliais/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , AVC Isquêmico/patologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Nexinas de Classificação/genética , Transfecção
14.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352699

RESUMO

The new coronavirus disease-2019 (COVID-19), which is spreading around the world and threatening people, is easily infecting a large number of people through airborne droplets; moreover, patients with hypertension, diabetes, obesity, and cardiovascular disease are more likely to experience severe conditions. Vascular endothelial dysfunction has been suggested as a common feature of high-risk patients prone to severe COVID-19, and measurement of vascular endothelial function may be recommended for predicting severe conditions in high-risk patients with COVID-19. However, fragmented vascular endothelial glycocalyx (VEGLX) is elevated in COVID-19 patients, suggesting that it may be useful as a prognostic indicator. Although the relationship between VEGLX and severe acute respiratory syndrome coronavirus 2 infections has not been well studied, some investigations into COVID-19 have clarified the relationship between VEGLX and the mechanism that leads to severe conditions. Clarifying the usefulness of VEGLX assessment as a predictive indicator of the development of severe complications is important as a strategy for confronting pandemics caused by new viruses with a high affinity for the vascular endothelium that may recur in the future.


Assuntos
COVID-19/patologia , Endotélio Vascular/patologia , Glicocálix/patologia , Doenças Vasculares/patologia , Células Endoteliais/patologia , Humanos , Pulmão/patologia , Pulmão/virologia , Prognóstico , SARS-CoV-2 , Doenças Vasculares/virologia
15.
Neurology ; 95(14): e1918-e1931, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32887784

RESUMO

OBJECTIVE: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. METHODS: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. RESULTS: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL-S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = -0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death (p < 0.001). CONCLUSION: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S.


Assuntos
Disfunção Cognitiva/patologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Degeneração Neural/patologia , Doenças Retinianas/patologia , Doenças Vasculares/patologia , Substância Branca/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico por imagem , Neuroimagem/métodos , Doenças Retinianas/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
16.
Proc Natl Acad Sci U S A ; 117(38): 23925-23931, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900929

RESUMO

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.


Assuntos
Envelhecimento/metabolismo , Amiloide/metabolismo , Antígenos de Superfície/metabolismo , Proteínas do Leite/metabolismo , Doenças Vasculares/metabolismo , Idoso de 80 Anos ou mais , Amiloide/genética , Animais , Antígenos de Superfície/genética , Aorta/metabolismo , Aorta/patologia , Química Encefálica/fisiologia , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Leite/genética , Doenças Vasculares/patologia
17.
Life Sci ; 260: 118398, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920004

RESUMO

AIMS: We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet (HFD)-fed rats. MAIN METHODS: Male Sprague-Dawley rats were fed a HFD with fructose 15% in drinking water for 16 weeks. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks. KEY FINDINGS: HFD-fed rats treated with nobiletin was significantly reduced obesity, hypertension, dyslipidemia and hyperinsulinemia. Nobiletin improved vascular endothelial function, restored creatinine clearance, and reduced plasma urea and creatinine levels, as well as urinary protein excretion. Nobiletin markedly alleviated vascular medial cross-sectional area (CSA) and collagen deposition, glomerular extracellular matrix (ECM) accumulation, and renal fibrosis. Nobiletin significantly elevated plasma adiponectin levels, together with upregulated adiponectin receptor 1 (AdipoR1) and suppressed transforming growth factor-ß1 (TGF-ß1) expression in kidney. In addition, an increase of plasma tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly attenuated after nobiletin treatment. SIGNIFICANCE: Our results suggest that nobiletin attenuates HFD-induced vascular and renal alterations in rats, which is possibly related to the modulation of AdipoR1 and TGF-ß1expression, and suppression of inflammation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Flavonas/farmacologia , Inflamação/prevenção & controle , Nefropatias/tratamento farmacológico , Receptores de Adiponectina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Doenças Vasculares/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Regulação da Expressão Gênica , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Adiponectina/genética , Fator de Crescimento Transformador beta1/genética , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia
20.
Arterioscler Thromb Vasc Biol ; 40(10): 2404-2407, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32762443

RESUMO

OBJECTIVE: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. CONCLUSIONS: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.


Assuntos
Infecções por Coronavirus/patologia , Células Endoteliais/citologia , Endotélio Vascular/patologia , Pneumonia Viral/patologia , Trombose/patologia , Doenças Vasculares/patologia , Autopsia , Biópsia por Agulha , Causas de Morte , Infecções por Coronavirus/mortalidade , Células Endoteliais/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pandemias , Pneumonia Viral/mortalidade , Medição de Risco , Trombose/etiologia , Trombose/mortalidade , Doenças Vasculares/mortalidade , Doenças Vasculares/fisiopatologia
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