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1.
J Biomed Nanotechnol ; 16(6): 810-826, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187578

RESUMO

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG2k-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis in vitro, which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE- / - mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after in vivo treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.


Assuntos
Aterosclerose , Nanopartículas , Animais , Aterosclerose/tratamento farmacológico , Autofagia , Fosfatos de Cálcio , Dexametasona/análogos & derivados , Células Endoteliais , Lipoproteínas LDL , Camundongos , Fosfatidiletanolaminas , Sirolimo
2.
Urologiia ; (5): 122-126, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33185359

RESUMO

Prostate cancer (PCa) remains a relevant public health concern and one of the main causes of morbidity and mortality worldwide. Coronary artery disease (CAD) with the underlying coronary artery atherosclerosis is the leading cause of global death. The interaction between modifiable and non-modifiable risk factors for these pathological conditions is discussed in the review. Elevated serum cholesterol, a known risk factor for CAD, can be associated with both development and progression of PCa. From this perspective, patients with atherosclerosis may represent a potential target group for PCa screening. Alternatively, patients with PCa should undergo examination for concomitant cardiovascular diseases as well as their risk factors. Statins are supposed to be potentially beneficial in treating atherosclerosis in men and reducing the risk of PCa development and progression.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Neoplasias da Próstata , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Fatores de Risco
3.
Zhongguo Zhong Yao Za Zhi ; 45(17): 4099-4111, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164394

RESUMO

The aim of this paper was to explore the mechanism of Xiaoyao Powder in treating atherosclerosis and depressive disorder with concept of "treating different diseases with same method" based on network pharmacology. TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and SymMap databases were used to search all the chemical components and targets related to Xiaoyao Powder. After preliminary screening, the network of "herbs-compounds-targets" was constructed. Through DisGeNET, CTD(Comparative Toxicogenomics Database) and TTD(Therapeutic Target Database), the targets of atherosclerosis and depressive disorder were obtained. The common targets were obtained by intersecting the herbal targets and disease targets. In order to screen the key common targets, STRING and Cytoscape were used to analyze the protein-protein interaction of common targets. BioGPS was used to obtain their distribution information in organs and tissues. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) analysis were conducted through Metascape. About 1 355 compounds of Xiaoyao Powder were found by TCMSP and Symmap database; 161 active compounds were screened out according to standard of oral bioavailability≥30% and drug like index≥0.18; 274 herbal targets were obtained and the "herbs-compounds-targets" network was constructed. About 1 004 atherosclerosis targets and 578 depressive disorder targets were obtained, and 37 common targets were obtained after intersection with herbal targets. By using STRING and Cytoscape for protein-protein interaction analysis, 18 key targets were screened. BioGPS showed that the key common targets were mainly distributed in heart, amygdala, pineal, liver and smooth muscle. Metascape was used for GO enrichment analysis and the results showed that there were 929 biological processes, 25 cell components and 23 molecular functions. Enrichment ana-lysis of KEGG showed that there were 108 signal pathways such as AGE-RAGE, HIF-1, FoxO, Th17 cell differentiation and IL-17 signal pathways, which were mainly related to neuroendocrine system, metabolism, immune inflammation and oxidative stress. In conclusion, the main mechanism of Xiaoyao Powder in treating atherosclerosis and depressive disorder with concept of "treating different diseases with same method" was related to neuroendocrine system, metabolism, immune inflammation and oxidative stress-related signal pathway, providing reference for further experimental verification, potential pharmacological mechanism and clinical application.


Assuntos
Aterosclerose , Transtorno Depressivo , Medicamentos de Ervas Chinesas , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Humanos , Medicina Tradicional Chinesa
4.
Rev Med Liege ; 75(11): 697-698, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33155440

RESUMO

Coronary aneurysm has an incidence of 1,1 to 4,9 % in patients undergoing a coronary angiography. Many etiologies may be accused, atherosclerosis is associated in up to 50 % of cases. We report the case of a 76-year-old patient with a large coronary aneurysm.


Assuntos
Aterosclerose , Aneurisma Coronário , Idoso , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Angiografia Coronária , Humanos
5.
Kyobu Geka ; 73(10): 725-730, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130756

RESUMO

Stroke is an important cause of morbidity and mortality after cardiovascular surgery and its incidence has been reported as 1.5 to 8.7%. Preexisting cerebrovasuclar disease, stenotic lesions of the carotid artery and atherosclerosis of the ascending aorta are known to be significant anatomic risk factors. To prevent perioperative stroke, it is important to discuss the onset mechanisms. Intraoperative stroke is mainly caused by the embolization of scattered atheroscrelotic plaque. Carotid duplex scanning and magnetic resonance imaging (MRI) are useful methods for the preoperative screening of cerebrovascular stenosis and plaque. Enhanced computed tomography (CT) is a powerful tool to estimate the presence of severe atheroscrelotic plaque in the aorta. When severe plaque is present, the manipulation, cannulation or clamping of the diseased aortic segment should be prevented. Insufficient oxygenated brain blood flow is thought to be another mechanism of intraoperative stroke. Impaired cerebral autoregulation during caridopulmonary bypass has been reported. Thus, it is recommended to maintain a high mean arterial pressure during cardiopulmonary bypass, especially in patients with cerebrovasuclar occlusive diseases. Postoperative stroke is mainly caused by embolization of the thrombus. To prevent this, excessive hypovolemia and atrial fibrillation should be avoided. Preemptive usage of beta blockers is one option for preventing postoperative atrial fibrillation.


Assuntos
Doenças da Aorta , Aterosclerose , Fibrilação Atrial , Acidente Vascular Cerebral , Aorta , Ponte Cardiopulmonar , Humanos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
7.
Biol Res ; 53(1): 44, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008472

RESUMO

BACKGROUND: Atherosclerosis (AS) is the main pathological basis of coronary heart disease, cerebral infarction and peripheral vascular disease, which seriously endanger people's life and health. In recent years, long non-coding RNA (lncRNA) has been found to be involved in gene expression regulation, but the research on AS is still in the initial stage. In this study, we mainly studied the role of HCG11 in patients with AS. Quantitative Real-time Polymerase Chain Reaction (QRT-PCR) was used to detect the expression of HCG11 and miR-144 in the serum of AS patients and healthy volunteers. Oxidation Low Lipoprotein (Ox-LDL), interleukin-6 (IL-6) and tumor necrosis factor α (TNF α) radiation were used to establish human vascular smooth muscle cells (VSMCs) in vitro model. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay. The apoptosis rate was determined by flow cytometry (FACS) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. The expression levels of Forkhead box protein F1 (FOXF1), B cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) were detected by qRT-PCR. Luciferase gene reporter and RNA pull down experiments confirmed the relationship between HCG11 and miR-144, miR-144 and FOXF1. RESULTS: This study showed that HCG11 was significantly upregulated in patients with AS, while miR-144 was down-regulated in patients with AS. Ox-LDL and IL-6 in VSMCs induced up-regulation of HCG11 and down-regulation of miR-144. Overexpression of HCG11 promoted the proliferation and inhibited apoptosis of VSMCs. Luciferase gene reporter gene assay showed that HCG11 could bind to miR-144, and miR-144 could bind to FOXF1. Overexpression of miR-144 reversed the effect of HCG11 on VSMCs. CONCLUSIONS: LncRNA HCG11 regulates proliferation and apoptosis of vascular smooth muscle cell through targeting miR-144-3p/FOXF1 axis.


Assuntos
Aterosclerose , Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , Miócitos de Músculo Liso/citologia , RNA Longo não Codificante/genética , Apoptose/genética , Aterosclerose/genética , Proliferação de Células/genética , Humanos , Músculo Liso Vascular/citologia
8.
Nat Commun ; 11(1): 5426, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110060

RESUMO

Novel atherosclerosis models are needed to guide clinical therapy. Here, we report an in vitro model of early atherosclerosis by fabricating and perfusing multi-layer arteriole-scale human tissue-engineered blood vessels (TEBVs) by plastic compression. TEBVs maintain mechanical strength, vasoactivity, and nitric oxide (NO) production for at least 4 weeks. Perfusion of TEBVs at a physiological shear stress with enzyme-modified low-density-lipoprotein (eLDL) with or without TNFα promotes monocyte accumulation, reduces vasoactivity, alters NO production, which leads to endothelial cell activation, monocyte accumulation, foam cell formation and expression of pro-inflammatory cytokines. Removing eLDL leads to recovery of vasoactivity, but not loss of foam cells or recovery of permeability, while pretreatment with lovastatin or the P2Y11 inhibitor NF157 reduces monocyte accumulation and blocks foam cell formation. Perfusion with blood leads to increased monocyte adhesion. This atherosclerosis model can identify the role of drugs on specific vascular functions that cannot be assessed in vivo.


Assuntos
Arteríolas/fisiopatologia , Aterosclerose/fisiopatologia , Arteríolas/química , Arteríolas/citologia , Aterosclerose/genética , Aterosclerose/metabolismo , Fenômenos Biomecânicos , Adesão Celular , Proliferação de Células , Células Cultivadas , Células Espumosas/citologia , Células Espumosas/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Modelos Biológicos , Monócitos/citologia , Monócitos/metabolismo , Óxido Nítrico/metabolismo , Engenharia Tecidual , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1127-1135, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051429

RESUMO

Long non-coding RNA (lncRNA) have been attracted attention due to its role in many diseases. Taurine up-regulated gene 1(TUG1)is a non-coding RNA of 7.1 kb in length, which locates on chromosome 22q12. More and more studies have found that TUG1 not only participates in the occurrence and development of tumors, but also plays an important role in the progression of diseases in cardiovascular system, endocrine system, nervous system and so on. It is expected to become the therapeutic targets and indicators for evaluating prognosis of a variety of diseases such as diabetes, myocardial ischemia, osteoarthritis, atherosclerosis and so on.


Assuntos
Aterosclerose , MicroRNAs , RNA Longo não Codificante , Humanos , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Taurina
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1096-1103, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051424

RESUMO

OBJECTIVES: Coronary atherosclerotic heart disease (CHD) is caused by coronary atherosclerosis, which leads to stenosis and even occlusion of the lumen, resulting in myocardial ischemia, and necrosis subsequently. Its prevalence has been high for a long time. The prevention and treatment of CHD are important. The study aimed to investigate the role of plasma levels of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like protein (MLKL) in patients with CHD and its clinical predictive value. METHODS: A total of 190 patients with CHD who were diagnosed by coronary angiography and 70 healthy subjects in cardiovascular department from September 2015 to May 2017 were enrolled in this study. Patients with CHD were assigned into 4 groups: Patients with stable angina pectoris (SAP, n=46), patients with unstable angina pectoris (UAP, n=56), patients with non-ST-segment elevation myocardial infarction (NSTEMI, n=42), and patients with ST-segment elevation myocardial infarction (STEMI, n=46). Patients with CHD were assigned into a single-vessel lesion group, a double-vessel lesion group, and a multi-vessel lesion group according to the results of coronary angiography, and the severity of coronary artery stenosis was determined by Gensini score. Plasma levels of RIPK1, RIPK3, and MLKL were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The plasma levels of RIPK1, RIPK3, and MLKL in patients with CHD were significantly higher than those in the controls (P<0.05). The plasma levels of RIPK1, RIPK3, and MLKL in the UAP group were significantly higher than those in the SAP group (P<0.05). The plasma levels of RIPK1, RIPK3, and MLKL in NSTEMI and STEMI group were significantly higher than those in the UAP group (P<0.05). There was no significant difference between the NSTEMI group and STEMI group (P>0.05). The plasma levels of RIPK1, RIPK3 and MLKL were significantly increased with numbers of coronary artery lesions (P<0.05), which were positively correlated with Gensini scores. The multivariate logistic regression analysis showed that plasma levels of RIPK1, RIPK3, and MLKL were independent risk factors for severe coronary artery stenosis.The average period of follow-up was 24 months after hospital discharge. The patients were divided into 2 groups according to whether they had major adverse cardiovascular events (MACE). Compared with patient without MACE, patient with MACE had higher levels of RIPK1, RIPK3, and MLKL (P<0.05). Receiver operator characteristic (ROC) curve analysis showed that the area under curve of RIPK1 was 0.72 (P<0.001), the area under curve of RIPK3 was 0.83 (P<0.001), and the area under curve of MLKL was 0.75 (P<0.001). CONCLUSIONS: Plasma levels of RIPK1, RIPK3, and MLKL are closely related to CHD, and they have predictive value for the prognosis evaluation for patients with CHD.


Assuntos
Aterosclerose , Estenose Coronária , Angiografia Coronária , Humanos , Necrose , Proteínas Quinases , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 17-23, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016672

RESUMO

OBJECTIVE: To evaluate the hemostasis of plasma aminothiols in different subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 177 patients, aged 62 (55-68) years, admitted in the first 8-24 hours since IS onset. The pathogenetic subtype of IS was clarified according to the results of clinical and instrumental examination by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Determination of the total plasma aminothiols levels, their reduced forms and redox status was performed using the ultra-efficient Acquity H-Class UPLC liquid chromatograph (Waters, CSHA). RESULTS: Large-artery atherosclerosis was diagnosed in 24.3% patients, cardioembolic stroke in 20.3%, lacunar stroke in 55.4%. Significant differences in total levels of cysteine (Cys), glutathione (Gsh) and homocysteine (Hcy) were identified in patients with different IS subtypes. Patients with large-artery atherosclerosis and lacunar stroke showed the highest level of Hcy, patients with cardioembolic stroke had the lowest levels of Cys and Gsh. CONCLUSION: Total levels of plasma aminothiols are associated with different subtypes of IS.


Assuntos
Aterosclerose , Isquemia Encefálica/complicações , Cisteína , Glutationa , Homocisteína , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/sangue , Cisteína/sangue , Glutationa/sangue , Homocisteína/sangue , Humanos , Pessoa de Meia-Idade , Oxirredução
13.
Rinsho Shinkeigaku ; 60(10): 693-698, 2020 Oct 24.
Artigo em Japonês | MEDLINE | ID: mdl-32893244

RESUMO

We report the case of a 66-year-old female with hemiplegia cruciata and severe facial pain due to infarction of the cervicomedullary junction. She presented to the hospital with complaints of acute-onset left facial pain and gait disturbance. Neurological examination revealed narrow left palpebral fissure, severe left facial pain and hypothermoesthesia, weakness predominantly in the left upper and right lower extremities, decreased pain and temperature sensation in the right lower extremity, decreased vibration sensation in the left lower extremity, hyperreflexia in the left upper extremity, and mild ataxia in the left upper and lower extremities. Brain MRI revealed a high-intensity lesion in the left cervicomedullary junction on diffusion-weighted and fluid-attenuated inversion recovery images. Hemiplegia cruciata due to the pyramidal tract injury at the cervicomedullary junction is an uncommon clinical manifestation. However, in patients with hemiplegia cruciata, identifying the lesion location may be difficult. Clinicians should consider the possibility of pyramidal decussation lesions. Anatomical differences, in the course of pyramidal tract fibers between the upper and lower limbs have been considered in the pyramidal decussation. Hemiplegia cruciata in this case was primarily caused by the impairment of the left upper limb pyramidal fibers after the pyramidal decussation and the right lower limb pyramidal fibers before the pyramidal decussation.


Assuntos
Aterosclerose/complicações , Medula Cervical/irrigação sanguínea , Dor Facial/etiologia , Hemiplegia/diagnóstico , Hemiplegia/etiologia , Infarto/diagnóstico , Infarto/etiologia , Bulbo/irrigação sanguínea , Artéria Vertebral , Idoso , Medula Cervical/diagnóstico por imagem , Extremidades/inervação , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Imagem por Ressonância Magnética , Bulbo/diagnóstico por imagem , Debilidade Muscular/etiologia , Tratos Piramidais
14.
Int J Nanomedicine ; 15: 6137-6152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884268

RESUMO

Background: Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions. Materials and Methods: Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 (89Zr4+). The targeting potential of this probe was compared with unspecific 89Zr-HSA and 18F-FDG in an experimental model of atherosclerosis (Apoe-/- mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls. Results: PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of 89Zr-Mal-HSA in the atherosclerotic lesions of Apoe-/- mice. The maximum standardized uptake values (SUVmax) for 89Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe-/- mice than in control WT mice, whereas no difference in SUVmax was observed for 18F-FDG in the same animals. 89Zr-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (P<0.01) for Apoe-/- mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (P<0.001) for 89Zr-Mal-HSA compared with unspecific 89Zr-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of 89Zr-Mal-HSA in the aortas of Apoe-/- mice than in WT mice (9.4±1.4 vs 0.8±0.3%; P<0.001). Conclusion: 89Zr radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of Apoe-/- mice, as demonstrated by quantitative in vivo PET/MRI. 89Zr-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.


Assuntos
Aterosclerose/diagnóstico por imagem , Maleatos/química , Imagem Molecular/métodos , Radioisótopos , Albumina Sérica Humana/química , Zircônio , Animais , Aorta/diagnóstico por imagem , Aorta/patologia , Aterosclerose/patologia , Autorradiografia , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18 , Humanos , Marcação por Isótopo , Macrófagos/patologia , Imagem por Ressonância Magnética , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Sondas Moleculares/química , Sondas Moleculares/farmacocinética , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Tomografia por Emissão de Pósitrons , Radioisótopos/química , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/química , Distribuição Tecidual , Zircônio/química , Zircônio/farmacocinética
15.
J Stroke Cerebrovasc Dis ; 29(10): 105178, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912501

RESUMO

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.


Assuntos
Doenças da Aorta/complicações , Aterosclerose/complicações , Colesterol/análise , Embolia Intracraniana/terapia , Trombose Intracraniana/terapia , Placa Aterosclerótica , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/metabolismo , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Cristalização , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/etiologia , Masculino , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
16.
J Biomed Nanotechnol ; 16(4): 467-480, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32970979

RESUMO

We developed a vaccine formulation containing ApoB derived P210 peptides as autoantigens, retinoic acid (RA) as an immune enhancer, both of which were delivered using PLGA nanoparticles. The formula was used to induce an immune response in 12-week-old male Apoe-/- mice with pre-existing atherosclerotic lesions. The nanotechnology platform PRINT® was used to fabricate PLGA nanoparticles that encapsulated RA inside and adsorbed the P210 onto the particle surface. In this study, we demonstrated that immunization of Apoe-/- mice with the formulation was able to considerably attenuate atherosclerotic lesions, accompanied by increased P210 specific IgM and another oxidized lipid derived autoantigen, M2AA, specific IgG autoantibodies, and decreased the inflammatory response, as compared to the P210 group with Freund's adjuvant. Our formulation represents an exciting technology to enhance the efficacy of the P210 vaccine.


Assuntos
Aterosclerose , Nanopartículas , Animais , Apolipoproteína B-100 , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Masculino , Camundongos , Peptídeos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tretinoína
17.
PLoS Pathog ; 16(9): e1008885, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976527

RESUMO

Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded.


Assuntos
Aterosclerose/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CX3CL1/metabolismo , Infecções por HIV/metabolismo , Interleucina-15/metabolismo , Idoso , Animais , Células Endoteliais/metabolismo , Humanos , Macaca mulatta/metabolismo , Receptores de Quimiocinas/metabolismo
18.
Rev. cuba. estomatol ; 57(3): e2976, jul.-set. 2020. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1126523

RESUMO

RESUMEN Introducción: La periodontitis se caracteriza por ser una inflamación mediada por el huésped y asociada a microbios que producen la pérdida de la adherencia periodontal. Una infección focal localizada como la enfermedad periodontal podría conducir a una inflamación sistémica. La disfunción endotelial vascular se ha asociado con una variedad de enfermedades y factores de riesgo para la aterosclerosis, que incluyen la edad, hipertensión arterial, dislipidemias, diabetes, tabaquismo, enfermedades cardiovasculares específicas como arteriopatía coronaria, cerebral y procesos infecciosos e inflamatorios como enfermedad periodontal. Objetivo: Evaluar los efectos del tratamiento periodontal no quirúrgico sobre la función endotelial de los pacientes con periodontitis crónica mediante una revisión de ensayos clínicos aleatorizados. Métodos: Se utilizó una estrategia de búsqueda primaria en combinación de vocabulario controlado y términos de texto libre para la elaboración de una estrategia de búsqueda en MEDLINE a través de PubMed, mediante el PubMed Advanced Search Builder el 5 de julio de 2019. Análisis e integración de la información: Fueron seleccionados 29 artículos de 2214. Para la elección se tuvo en cuenta que fueran estudios en humanos donde estuvieran relacionadas las variables de estudio. Del 100 por ciento de los artículos seleccionados se encontró que el 37,9 por ciento pertenecían a estudios de casos y controles, el 31 por ciento pertenecían a estudios transversales, el 10,34 por ciento a estudios de cohorte y solo 20,6 por ciento fueros estudios de ensayos clínicos, de los cuales solo 3 artículos (10 por ciento) fueron seleccionados para esta revisión. Conclusiones: La terapia periodontal no presenta un efecto sobre la función endotelial en un periodo de 3 meses, sin embargo, a los 6 meses se reporta una mejoría en la función endotelial(AU)


ABSTRACT Introduction: Periodontitis is characterized by being an inflammation mediated by the host and associated with microbes that produce, the loss of periodontal adhesion. A localized focal infection such as periodontal disease could lead to systemic inflammation. Vascular endothelial dysfunction has been associated with a variety of pathologies and risk factors for atherosclerosis, including age, hypertension, dyslipidemias, diabetes, smoking, specific cardiovascular pathologies such as coronary artery disease, cerebral, inflammatory, and infectious processes such as periodontal disease. Objective: Assess the effects of non-surgical periodontal treatment on the endothelial function of patients with chronic periodontitis through a review of randomized clinical trials. Methods: We used a primary search strategy using a combination of controlled vocabulary and free text terms based on the MEDLINE search strategy through PubMed using the PubMed Advanced Search Builder on July 05, 2019. Analysis and integration of the information: 29 articles of 2214 were selected because they are human studies where the study variables are related. 100 percent of the selected articles found that 37.9 percent belonged to case-control studies, 31 percent belonged to cross-sectional studies, 10.34 percent to cohort studies and only 20.6 percent were clinical trial studies, of which only 3 articles (10 percent) were selected for this review. Conclusions: Periodontal therapy does not have an effect on endothelial function in a period of 3 months, however at 6 months an improvement in endothelial function was reported(AU)


Assuntos
Humanos , Periodontite/fisiopatologia , Literatura de Revisão como Assunto , Doenças Cardiovasculares/etiologia , Fatores de Risco , Aterosclerose/etiologia , Estudos de Casos e Controles , Estudos Transversais , Estudos de Coortes , Bases de Dados Bibliográficas
19.
Hipertens. riesgo vasc ; 37(3): 108-114, jul.-sept. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193519

RESUMO

INTRODUCCIÓN Y OBJETIVOS: Las alteraciones del sistema nervioso autónomo fueron propuestas como precursoras en la génesis y perpetuación de la aterosclerosis hace ya mucho tiempo. Nuestro objetivo fue determinar si existe asociación entre la presencia de aterosclerosis carotídea y la función autonómica evaluada mediante la variabilidad de la frecuencia cardíaca. MÉTODOS: A través de un estudio prospectivo de casos y controles investigamos la variabilidad de la frecuencia cardíaca en 5 min y la presencia de aterosclerosis carotídea mediante ultrasonografía en 54 pacientes que dividimos en 2 grupos según la presencia (+) o ausencia (−) de placas ateroscleróticas en carótidas (ATE). Se analizó la variabilidad de frecuencia cardíaca en dominio de frecuencia en el espectro de alta frecuencia, baja frecuencia, cociente alta/baja frecuencia y potencia espectral total. RESULTADOS: Sobre una población de 54 individuos sin enfermedad cardiovascular establecida evaluados en forma consecutiva, se detectaron 26 individuos (48%) portadores de ATE+. Se observó una reducción en la variabilidad de la frecuencia cardíaca en el grupo ATE+ representada por el espectro de baja frecuencia (LF) (p < 0,0001). La actividad parasimpática específicamente representada por el componente espectral de alta frecuencia también resultó menor en el grupo ATE+en análisis univariado (p < 0,0001) al igual que la potencia espectral total (p < 0,0001), un índice de regulación autonómica integral. No se encontraron diferencias significativas cuando se analizó el balance autonómico de baja y alta frecuencia (LF/HF) (p = 0,1598). En un modelo de regresión logística solo la presión arterial sistólica y el poder espectral total resultaron predictores independientes de ATE+. CONCLUSIÓN: Verificamos una disminución en la variabilidad de la frecuencia cardíaca en sujetos con aterosclerosis carotídea, que se estableció tanto a través de sus componentes espectrales como de la potencia espectral total, no así a través de la valoración del balance autonómico. La potencia espectral total, en principio, sería un método correcto de evaluación autonómica en este grupo de pacientes


INTRODUCTION AND OBJECTIVES: Alterations of the sympathetic and parasympathetic nervous system have been proposed as precursors of the genesis and perpetuation of atherosclerosis for a long time. The objective of this study is to determine if there is an association between the presence of carotid atherosclerosis and the reduction in heart rate variability. METHODS: Using a prospective case-control design, the heart rate variability and the presence of carotid atherosclerosis was investigated in 54 patients, divided into 2 groups according to the presence or absence of carotid atherosclerosis. An analysis was made of the heart rate variability variables of the frequency (spectral) domain in high frequency band, low frequency band, parasympathetic autonomic balance, and the total spectral band. RESULTS: Of the 54 individuals evaluated without previous cardiovascular disease consecutively, 26 of them (48%) presented with subclinical carotid atherosclerosis (ATE+). A reduction in heart rate variability was observed in the ATE+group represented by the low frequency (LF) spectrum (P < .0001). The parasympathetic activity specifically represented in the high frequency (HF) band was also lower in the ATE+group in the univariate analysis (P < .0001), same as the total spectral power (P < .0001), an index of integral autonomic regulation. No significant differences were found in the LF/HF analysis (P = .1598). After analysing variables with significant differences in the univariate analysis with a logistic regression model, only systolic blood preassure and the total spectral power were shown to be independent predictors of ATE+. CONCLUSION: A reduction in heart rate variability was found in subjects with carotid atherosclerosis. Some spectral components of heart rate variability, like low frequency or total spectral power, were better predictors of carotid atherosclerosis than the parasympathetic autonomic balance. In this study it seems that total spectral power is an adequate measurement for analysing autonomic function


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Doenças do Sistema Nervoso Autônomo/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca , Aterosclerose/diagnóstico por imagem , Estudos de Viabilidade , Estudos Prospectivos , Modelos Logísticos , Pressão Sanguínea , Estudos de Casos e Controles , Antropometria , Hipolipemiantes/uso terapêutico , Índice de Massa Corporal , Hipertensão/terapia , Fatores de Risco
20.
Stroke ; 51(10): 3156-3168, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32897811

RESUMO

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.


Assuntos
Aterosclerose/epidemiologia , Infecções/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Aterosclerose/imunologia , Aterosclerose/fisiopatologia , Bacteriemia/epidemiologia , Bacteriemia/imunologia , Bacteriemia/fisiopatologia , Betacoronavirus , Doença Crônica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/fisiopatologia , Endotélio/fisiopatologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções/imunologia , Infecções/fisiopatologia , Inflamação/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Pandemias , Ativação Plaquetária , Agregação Plaquetária , Pneumonia/epidemiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/imunologia , Trombose/epidemiologia , Trombose/imunologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/fisiopatologia
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