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1.
J Stroke Cerebrovasc Dis ; 30(1): 105463, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33242780

RESUMO

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.


Assuntos
Aterosclerose/terapia , Procedimentos Endovasculares , Trombectomia , Terapia Trombolítica , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Circulação Cerebrovascular , Procedimentos Endovasculares/efeitos adversos , Europa (Continente) , Humanos , /etiologia , Sistema de Registros , Medição de Risco , Fatores de Risco , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
2.
Ecotoxicol Environ Saf ; 208: 111440, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33039868

RESUMO

Fine particulate matter (PM2.5) exposure is intimately linked to atherosclerosis. Defective macrophages autophagy plays an accelerated role in advanced atherosclerosis, however, whether macrophages autophagy has been implicated in the development of PM2.5-induced atherosclerosis has not been analyzed in full detail. Here we aimed to investigate the association between macrophages autophagy and PM2.5-induced atherosclerosis, as well as the underlying mechanisms. ApoE-/- mice were randomly exposed to PM2.5 or filtered air for 3 months, macrophage RAW264.7 cells were isolated and were stimulated with PM2.5 sample, selective inhibitors of PI3K/Akt/mTOR pathway LY294002, triciribine, and rapamycin were used in vitro and in vivo to detect the potential mechanisms. We found that PM2.5 could significantly accelerate atherosclerotic plaque formation in ApoE-/- mice, increase serum levels of TC and LDL-C, accelerate lipid accumulation in RAW264.7 cells, elevate serum and supernatant levels of IL-6, TNF-α and hs-CRP, decrease the number of autophagosomes in aortic plaque and RAW264.7 cells, reduce the expressions of autophagy-related genes LC3-I, LC3-II and Beclin1 in aortic tissues and RAW264.7 cells but increase the expression of autophagy regulator p62, elevate PI3K, Akt and mTOR distributions in aorta, and increase p-PI3K, p-Akt and p-mTOR protein expressions in aorta and RAW264.7 cells. However, these effects of PM2.5 were aggravated with the administration of LY294002, triciribine, or rapamycin. This study indicated that the PI3K/Akt/mTOR pathway is involved in the suppression of autophagy induced by PM2.5 in macrophages, the accelerated effect of PM2.5 on atherosclerosis was mediated by down-regulation of macrophages autophagy via activating the PI3K/Akt/mTOR signaling pathway.


Assuntos
Poluentes Atmosféricos/toxicidade , Apolipoproteínas E/metabolismo , Aterosclerose/fisiopatologia , Autofagia/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Autofagossomos/metabolismo , Proteína Beclina-1/metabolismo , Cromonas , Masculino , Camundongos , Camundongos Knockout , Morfolinas , Fosfatidilinositol 3-Quinases/metabolismo , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
3.
Medicine (Baltimore) ; 99(50): e23730, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327364

RESUMO

BACKGROUND: Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases, and its pathogenesis is complex. Recent studies revealed a significant role of gut microbiota in the onset and development of atherosclerosis. Traditional Chinese medicine has rich clinical experience and unique advantages in the treatment of atherosclerosis. A large number of studies have proved that traditional Chinese medicine has the functions of reducing blood lipid, regulating gut microbiota, and resisting inflammation. The aim of this systematic review is to observe the randomized controlled trial of traditional Chinese medicine in treating gut microbiota, so as to evaluate the effectiveness and safety of traditional Chinese medicine in treating atherosclerosis patients. METHODS: The English database (PubMed, Web of Science, Embase, the Cochrane Library) and Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science, and Technology Periodic Database, Wanfang Database, and China Biomedical Literature Database) will be searched up to October 2020. We will also manually search the Chinese clinical trial register, conference papers, and unpublished studies or references. Randomized control trials of traditional Chinese medicine treatment of atherosclerosis were collected comprehensively, and 2 researchers will independently screen literature, data extraction, and evaluation the quality of literature methodology. The primary outcomes are lipid metabolism and gut microbiota and their metabolites. The secondary outcomes are the change of inflammatory markers. Meta-analysis was performed by RevMan 5.3.5 software. The Grades of Recommendation, Assessment, Development, and Evaluation will be used to evaluate the outcome quality of evidence. RESULTS: This study will comprehensively review the existing evidence of traditional Chinese medicine in treating atherosclerosis from the perspective of gut microbiota. CONCLUSION: This study will provide information on the effectiveness and safety of traditional Chinese medicine in treating atherosclerosis from the perspective of gut microbiota. UNIQUE INPLASY NUMBER: INPLASY2020110056.


Assuntos
Aterosclerose/prevenção & controle , Aterosclerose/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Biomarcadores , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
4.
Nat Commun ; 11(1): 6135, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262333

RESUMO

Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis. Using RNA-seq profiling of the intima of lesions, here we identify a macrophage-specific lncRNA MAARS (Macrophage-Associated Atherosclerosis lncRNA Sequence). Aortic intima expression of MAARS increases by 270-fold with atherosclerotic progression and decreases with regression by 60%. MAARS knockdown reduces atherosclerotic lesion formation by 52% in LDLR-/- mice, largely independent of effects on lipid profile and inflammation, but rather by decreasing macrophage apoptosis and increasing efferocytosis in the vessel wall. MAARS interacts with HuR/ELAVL1, an RNA-binding protein and important regulator of apoptosis. Overexpression and knockdown studies verified MAARS as a critical regulator of macrophage apoptosis and efferocytosis in vitro, in an HuR-dependent manner. Mechanistically, MAARS knockdown alters HuR cytosolic shuttling, regulating HuR targets such as p53, p27, Caspase-9, and BCL2. These findings establish a mechanism by which a macrophage-specific lncRNA interacting with HuR regulates apoptosis, with implications for a broad range of vascular disease states.


Assuntos
Aterosclerose/metabolismo , Núcleo Celular/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Apoptose , Aterosclerose/genética , Aterosclerose/fisiopatologia , Núcleo Celular/genética , Proteína Semelhante a ELAV 1/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Transporte Proteico , RNA Longo não Codificante/genética , Especificidade da Espécie
6.
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
7.
Metabolism ; 113: 154395, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058850

RESUMO

ApoCIII has a well-recognized role in triglyceride-rich lipoproteins metabolism. A considerable amount of data has clearly highlighted that high levels of ApoCIII lead to hypertriglyceridemia and, thereby, may influence the risk of cardiovascular disease. However, recent findings indicate that ApoCIII might also act beyond lipid metabolism. Indeed, ApoCIII has been implicated in other physiological processes such as glucose homeostasis, monocyte adhesion, activation of inflammatory pathways, and modulation of the coagulation cascade. As the inhibition of ApoCIII is emerging as a new promising therapeutic strategy, the complete understanding of multifaceted pathophysiological role of this apoprotein may be relevant. Therefore, the purpose of this work is to review available evidences not only related to genetics and biochemistry of ApoCIII, but also highlighting the role of this apoprotein in triglyceride and glucose metabolism, in the inflammatory process and coagulation cascade as well as in cardiovascular disease.


Assuntos
Apolipoproteína C-III/metabolismo , Aterosclerose/metabolismo , Doenças Metabólicas/metabolismo , Triglicerídeos/metabolismo , Apolipoproteína C-III/genética , Aterosclerose/fisiopatologia , Coagulação Sanguínea , Glicemia/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Doenças Metabólicas/fisiopatologia
8.
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
9.
Arterioscler Thromb Vasc Biol ; 40(11): 2569-2576, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32878476

RESUMO

Atherosclerosis is orchestrated by complex interactions between vascular and inflammatory cells. Traditionally, it has been considered to be an intimal inflammatory disease, characterized by endothelial dysfunction, inflammatory cell recruitment, lipid oxidation, and foam cell formation. This inside-out signaling paradigm has been accepted as dogma for many years, despite the fact that inflammatory cells are far more prevalent in the adventitia compared with the intima. For decades, the origin of adventitial inflammation in atherosclerosis was unknown. The fact that these inflammatory cells were observed to cluster at the margin of perivascular adipose tissues-a unique and highly inflammatory adipose depot that surrounds most atherosclerosis-prone blood vessels-has stimulated interest in perivascular adipose tissue-mediated outside-in signaling in vascular pathophysiology, including atherosclerosis. The phenotype of perivascular adipocytes underlies the functional characteristics of this depot, including its role in adventitial inflammatory cell recruitment, trafficking to the intima via the vasa vasorum, and atherosclerosis perturbation. This review is focused on emerging concepts pertaining to outside-in signaling in atherosclerosis driven by dysfunctional perivascular adipose tissues during diet-induced obesity and recent strategies for atherosclerosis prediction and prognostication based upon this hypothesis.


Assuntos
Adipócitos/metabolismo , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Aterosclerose/metabolismo , Vasos Sanguíneos/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Animais , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Comunicação Celular , Humanos , Inflamação/patologia , Inflamação/fisiopatologia , Placa Aterosclerótica , Transdução de Sinais
10.
BMC Cardiovasc Disord ; 20(1): 353, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32731902

RESUMO

BACKGROUND: Determining the risk factors for brachial-ankle pulse wave velocity (baPWV) may help to identify people susceptible to diabetic atherosclerosis and could prevent diabetic macrovascular complications in the early stages. We aim to comprehensively investigate risk factors contributing to arterial stiffness in patients with and without diabetes. METHODS: BaPWV was measured in 5651 individuals who attended health check-ups at baseline and follow-up. Lasso regression was used to screen for risk factors. Mixed models and multiple linear regressions were subsequently established to evaluate the effect size of the potential risk factors on baPWV and PWV change rates. All analyses were stratified by diabetes. Mediation analysis was also conducted to demonstrate the mechanisms of arterial stiffness in patients with diabetes. RESULTS: In lasso regression, postprandial 2-h glucose (P2hG), systolic blood pressure (SBP) and age were associated with baPWV regardless of diabetes. Platelet counts (PLT), mean corpuscular volume (MCV) and coronary heart disease (CHD) were associated with baPWV in patients with diabetes. In the mixed models, PLT were positively associated with baPWV in patients with diabetes (ßplatelet, perSD = 25.80; 18.26-33.33). Elevated PLTs could also significantly increase the PWV change rate in patients with diabetes (ßplatelet, perSD = 54.05; 10.00-107.10). In mediation analysis, diabetes had a significant average direct effect on baPWV. The average causal mediation effect (ACME) of PLTs was 1.76, with a range of 0.17 to 3.70. CONCLUSIONS: Elevated PLT counts can increase baPWV in diabetes and are a potential mediator between diabetes and atherosclerosis.


Assuntos
Aterosclerose/fisiopatologia , Plaquetas , Diabetes Mellitus/sangue , Rigidez Vascular , Adulto , Idoso , Índice Tornozelo-Braço , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Pequim/epidemiologia , Glicemia/metabolismo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Análise de Onda de Pulso , Fatores de Risco
11.
Actual. osteol ; 16(2): 140-153, mayo.-ago. 2020. ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-1129814

RESUMO

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)


Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)


Assuntos
Humanos , Masculino , Feminino , Osteogênese/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Aterosclerose/tratamento farmacológico , Calcificação Vascular/tratamento farmacológico , Osteogênese/fisiologia , Menopausa , Doenças Cardiovasculares/complicações , Osteoporose Pós-Menopausa , Remodelação Óssea , Genisteína/uso terapêutico , Fitoestrógenos/classificação , Fitoestrógenos/farmacologia , Aterosclerose/fisiopatologia , Estrogênios/biossíntese , Calcificação Vascular/fisiopatologia , Calcificação Vascular/metabolismo
12.
Arterioscler Thromb Vasc Biol ; 40(10): 2408-2424, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32847388

RESUMO

OBJECTIVE: microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results: We have used an inducible endothelium-specific knock-in mouse model to address the role of miR-217 in vascular function and atherosclerosis. miR-217 reduced NO production and promoted endothelial dysfunction, increased blood pressure, and exacerbated atherosclerosis in proatherogenic apoE-/- mice. Moreover, increased endothelial miR-217 expression led to the development of coronary artery disease and altered left ventricular heart function, inducing diastolic and systolic dysfunction. Conversely, inhibition of endogenous vascular miR-217 in apoE-/- mice improved vascular contractility and diminished atherosclerosis. Transcriptome analysis revealed that miR-217 regulates an endothelial signaling hub and downregulates a network of eNOS (endothelial NO synthase) activators, including VEGF (vascular endothelial growth factor) and apelin receptor pathways, resulting in diminished eNOS expression. Further analysis revealed that human plasma miR-217 is a biomarker of vascular aging and cardiovascular risk. CONCLUSIONS: Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease.


Assuntos
Envelhecimento/metabolismo , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Placa Aterosclerótica , Fatores Etários , Idoso de 80 Anos ou mais , Envelhecimento/genética , Animais , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Estudos de Casos e Controles , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Modelos Animais de Doenças , Células Endoteliais/patologia , Feminino , Hemodinâmica , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
13.
PLoS One ; 15(8): e0238112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857805

RESUMO

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE-/- mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. All in vivo MR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE-/- mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.


Assuntos
Aorta/diagnóstico por imagem , Imagem por Ressonância Magnética , Placa Aterosclerótica/diagnóstico por imagem , Animais , Aorta/patologia , Aorta/fisiopatologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Peso Corporal , Dieta Ocidental , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Estudos Longitudinais , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Camundongos Knockout , Placa Aterosclerótica/patologia , Placa Aterosclerótica/fisiopatologia , Distribuição Aleatória , Fluxo Sanguíneo Regional , Estresse Mecânico
14.
Am J Physiol Heart Circ Physiol ; 319(3): H547-H556, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32734819

RESUMO

Tobacco cigarette (TC) smoking has never been lower in the United States, but electronic cigarette (EC) vaping has reached epidemic proportions among our youth. Endothelial dysfunction, as measured by flow-mediated vasodilation (FMD) is a predictor of future atherosclerosis and adverse cardiovascular events and is impaired in young TC smokers, but whether FMD is also reduced in young EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic tobacco cigarette (TC) smoking and electronic cigarette (EC) vaping on FMD. FMD was compared in 47 nonsmokers (NS), 49 chronic EC vapers, and 40 chronic TC smokers at baseline and then after EC vapers (n = 31) and nonsmokers (n = 47) acutely used an EC with nicotine (ECN), EC without nicotine (EC0), and nicotine inhaler (NI) at ~4-wk intervals and after TC smokers (n = 33) acutely smoked a TC, compared with sham control. Mean age (NS, 26.3 ± 5.2 vs. EC, 27.4 ± 5.45 vs. TC, 27.1 ± 5.51 yr, P = 0.53) was similar among the groups, but there were more female nonsmokers. Baseline FMD was not different among the groups (NS, 7.7 ± 4.5 vs. EC:6.6 ± 3.6 vs. TC, 7.9 ± 3.7%∆, P = 0.35), even when compared by group and sex. Acute TC smoking versus control impaired FMD (FMD pre-/postsmoking, -2.52 ± 0.92 vs. 0.65 ± 0.93%∆, P = 0.02). Although the increase in plasma nicotine was similar after EC vapers used the ECN versus TC smokers smoked the TC (5.75 ± 0.74 vs. 5.88 ± 0.69 ng/mL, P = 0.47), acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD compared with that in nonsmokers was not present at baseline. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose" (estimated by change in plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.NEW & NOTEWORTHY In our study of otherwise healthy young people, baseline flow-mediated dilation (FMD), a predictor of atherosclerosis and increased cardiovascular risk, was not different among tobacco cigarette (TC) smokers or electronic cigarette (EC) vapers who had refrained from smoking, compared with nonsmokers. However, acutely smoking one TC impaired FMD in smokers, whereas vaping a similar EC "dose" (as estimated by change in plasma nicotine levels) did not. Finally, although it is reassuring that acute EC vaping did not acutely impair FMD, it would be premature and dangerous to conclude that ECs do not lead to atherosclerosis or increase cardiovascular risk.


Assuntos
Artéria Braquial/fisiopatologia , Fumar Cigarros/efeitos adversos , Vapor do Cigarro Eletrônico/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Endotélio Vascular/fisiopatologia , Vaping/efeitos adversos , Vasodilatação , Adulto , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Fumar Cigarros/fisiopatologia , Qualidade de Produtos para o Consumidor , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Medição de Risco , Fatores de Risco , Adulto Jovem
16.
Life Sci ; 257: 118013, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603818

RESUMO

AIMS: Emerging literature illustrates critical roles of long noncoding RNAs (lncRNAs) in the progression of atherosclerosis. However, the biological functions and mechanism by which lncRNAs regulate the atherosclerosis remain unclear. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidative low-density lipoprotein (ox-LDL). RNA and protein levels were respectively measured using RT-qPCR and western blot. Molecular interaction was detected using luciferase reporter assay and chromatin immunoprecipitation (ChIP). Proliferation and migration were measured using CCK-8 and wound healing assay. KEY FINDINGS: Here, results unveiled that lncRNA SNHG7 was remarkedly up-regulated in ox-LDL exposed HUVECs. Gain and loss of function experiments showed that the SNHG7 repressed the proliferation and migration of HUVECs. Mechanistically, transcription factor E2F1 was found to target the promoter region of lncRNA SNHG7 and accelerated its expression. Moreover, miR-186-5p was found to bind with the 3'-UTR of SNHG7, meanwhile miR-186-5p also bound with the MMP2 mRNA 3'-UTR. SIGNIFICANCE: In conclusion, these results show the essential roles of E2F1/SNHG7/miR-186-5p/MMP2 axis on the proliferation and migration of endothelial cells, providing a potential therapeutic target for atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Células Endoteliais/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Aterosclerose/fisiopatologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fator de Transcrição E2F1/metabolismo , Células Endoteliais/fisiologia , Técnicas de Silenciamento de Genes , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia
17.
Metabolism ; 111: 154321, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32712219

RESUMO

BACKGROUND: Lean muscle plays critical roles in physical functioning and metabolism. However, little is known regarding associations between muscle and mortality in adults. OBJECTIVE: The purpose was to evaluate associations between abdominal muscle quantity (area) and quality (density) with risk of all-cause mortality in a diverse cohort free of cardiovascular disease. DESIGN: Data were taken from the Abdominal Body Composition, Inflammation, and Cardiovascular Disease ancillary study of the Multi-Ethnic Study of Atherosclerosis prospective cohort study. Participants were adults (45-85 years) free of extant cardiovascular disease, and of Hispanic, African American, Chinese, or Caucasian descent. Of the original 6814 MESA participants, a random, representative sample (n = 1974) participated in the ancillary body composition study. Abdominal muscle area and density were measured from computed tomography scans spanning L2-L4. Muscle density was measured as attenuation in Hounsfield units, and area was quantified as cm2. Gender-stratified cox proportional hazard models assessed the risk of all-cause mortality across gender-specific quartiles of muscle area and density adjusting for confounders, with area and density entered simultaneously. RESULTS: At baseline, the mean age for men (n = 946) and women (n = 955) was 61.5 and 62.5 years and median follow-up time was 10.6 and 10.9 years, respectively. Muscle density was inversely associated with mortality, with the highest quartile of density showing a 73% reduction in risk for men (HR = 0.27, 95% CI = 0.14-0.51; p-trend<0.001) and 57% reduction for women (HR = 0.43, 95% CI = 0.18-1.01; p-trend = 0.04) compared to the lowest quartile when adjusting for mortality risk factors, lifestyle, BMI and visceral fat. There was no association between muscle area and all-cause mortality for men (p-trend = 0.58) or women (p-trend = 0.47). CONCLUSIONS: Greater abdominal muscle density, but not muscle area, is associated with markedly lower risk of all-cause mortality across a decade of follow up. Muscle quality may be a powerful predictor of mortality in community dwelling adults.


Assuntos
Músculos Abdominais/fisiopatologia , Aterosclerose/mortalidade , Aterosclerose/fisiopatologia , Composição Corporal/fisiologia , Grupos Étnicos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
19.
Expert Rev Cardiovasc Ther ; 18(9): 557-562, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700592

RESUMO

INTRODUCTION: Coronary artery disease (CAD) is the major cause of death of cardiovascular disease. It is initiated by atherosclerosis, which narrows the coronary arteries and limits blood flow and oxygen to the heart. Multiple pathophysiological conditions within the arteries, such as arterial wall thickening, endothelial dysfunction, and arterial stiffening, are associated with the development of atherosclerosis. AREAS COVERED: We introduce a new concept of 'intravascular multimorbidity,' the presence and integration of multiple pathophysiological conditions within the arteries. We also introduce some measurements of intravascular multimorbidity and discuss how these measurements can be utilized in cardiac rehabilitation (CR). EXPERT OPINION: We propose that the measures of intravascular multimorbidity in different arteries may provide information on disease severity and serve as unique prognostic 'barometers' to disease progression in patients with CAD. By measuring the underlying disease mechanisms within the arteries and understanding individual variability of disease progression/regression, these measures may also provide a unique prognostic window in CR. The window into intravascular multimorbidity can help guide clinical strategies, for example, assessing progress and appropriate titration of exercise. Intravascular multimorbidity may represent an important opportunity for more researchers and clinical professions to evaluate patients in CR.


Assuntos
Reabilitação Cardíaca/métodos , Doenças Cardiovasculares/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/etiologia , Doença da Artéria Coronariana/complicações , Coração/fisiopatologia , Hemodinâmica , Humanos , Multimorbidade , Rigidez Vascular
20.
Cardiovasc Eng Technol ; 11(5): 544-559, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666327

RESUMO

PURPOSE: Atherosclerosis preferentially occurs near the junction of branching vessels, where blood recirculation tends to occur (Malek et al. in J Am Med Assoc 282(21):2035-2042, 1999, https://doi.org/10.1001/jama.282.21.2035 ). For decades, CFD has been used to predict flow patterns such as separation and recirculation zones in hemodynamic models, but those predictions have rarely been validated with experimental data. In the context of verification and validation (V&V), we first conduct a CFD benchmark calculation that reproduces the vortex detection experiments of Karino and Goldsmith (1980) with idealised branching blood vessels (Karino and Goldsmith in Trans. Am. Soc. Artif. Internal Organs 26:500-506, 1980). The critical conditions for the formation of recirculation vortices, the so-called critical Reynolds numbers, are the main parameters for comparison with the experimental data to demonstrate the credibility of the CFD workflow. We then characterise the wall shear stresses and develop a surrogate model for the size of formed vortices. METHODS: An automated parametric study generating more than 12,000 CFD simulations was performed, sweeping the geometries and flow conditions found in the experiments by Karino and Goldsmith. The flow conditions were restricted to steady-state laminar flow, with a range of inflow Reynolds numbers up to 350, with various flow ratios between the main branch outlet and side branch outlet. The side branch diameter was scaled relative to the main branch diameter, ranging from 1.05/3 to 3/3; and the branching angles ranged in size from [Formula: see text] to [Formula: see text]. Recirculation vortices were detected by the inversion of the velocity vector at certain locations, as well as by the inversion of the wall shear stress (WSS) vector. RESULTS: The CFD simulations demonstrated good agreement with the experimental data on the critical Reynolds numbers. The spatial distributions of WSS on each branch were analysed to identify potential regions of disease. Once a vortex is formed, the size of the vortex increases by the square root of the Reynolds number. The CFD data was fitted to a surrogate model that accurately predicts the vortex size without the need to run computationally more expensive CFD simulations. CONCLUSIONS: This benchmark study validates the CFD simulation of vortex detection in idealised branching vessels under comprehensive flow conditions. This work also proposes a surrogate model for the size of the vortex, which could reduce the computational requirements in the studies related to branching vessels and complex vascular systems.


Assuntos
Artérias/fisiopatologia , Aterosclerose/fisiopatologia , Hemodinâmica , Modelos Cardiovasculares , Artérias/patologia , Aterosclerose/patologia , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Humanos , Hidrodinâmica , Análise Numérica Assistida por Computador , Placa Aterosclerótica , Estresse Mecânico
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