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1.
Angiology ; 72(4): 303-314, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33601945

RESUMO

Atherosclerosis and inflammatory bowel disease (IBD) are often regarded as 2 distinct entities. The commonest manifestation of atherosclerosis is ischemic heart disease (IHD), and an association between IHD and IBD has been reported. Atherosclerosis and IBD share common pathophysiological mechanisms in terms of their genetics, immunology, and contributing environmental factors. Factors associated with atherosclerosis are implicated in the development of IBD and vice versa. Therefore, treatments targeting the common pathophysiology pathways may be effective in both conditions. The current review considers the pathophysiological pathways that are shared between the 2 conditions and discusses the implications for treatment and research.


Assuntos
Imunidade Adaptativa , Aterosclerose/etiologia , Imunidade Inata , Doenças Inflamatórias Intestinais/etiologia , Estilo de Vida , Polimorfismo de Nucleotídeo Único , Animais , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/terapia , Microbioma Gastrointestinal , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Fenótipo , Polimorfismo Genético , Medição de Risco , Fatores de Risco , Vitamina D/imunologia
2.
Life Sci ; 276: 118957, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524421

RESUMO

The main pathological feature of atherosclerosis is lipid metabolism disorder and inflammation. Macrophages, as the most important immune cells in the body, run through the beginning and end of disease development. After macrophages overtake the atherosclerosis-susceptible area apolipoprotein low-density lipoprotein ox-LDL, they transform into foam cells that adhere to blood vessels and recruit a large number of pro-inflammatory factors to initiate the disease. Promoting the outflow of lipids in foam cells and alleviating inflammation have become the basic ideas for the study of atherosclerosis treatment strategies. The polarization of macrophages refers to the estimation of the activation of macrophages at a specific point in space and time. Determining the proportion of different macrophage phenotypes in the plaque can help identify delay or prevent disease development. However, the abnormal polarization of macrophages and the accumulation of lipid also affect the growth state of cells to some extent, thus aggravate the influence on plaque area and stability. Besides, overactive or deficient autophagy of macrophages may also lead to cell death and participate in lipid metabolism and inflammation regression. In this paper, the role of macrophages in atherosclerosis was discussed from three aspects: polarization, death, and autophagy.


Assuntos
Aterosclerose/patologia , Autofagia , Inflamação/patologia , Ativação de Macrófagos , Macrófagos/patologia , Animais , Aterosclerose/imunologia , Humanos , Inflamação/imunologia , Macrófagos/imunologia
3.
Molecules ; 26(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401401

RESUMO

There is a high level of interest in identifying metabolites of endogenously produced or dietary compounds generated by the gastrointestinal (GI) tract microbiota, and determining the functions of these metabolites in health and disease. There is a wealth of compelling evidence that the microbiota is linked with many complex chronic inflammatory diseases, including atherosclerosis. Macrophages are key target immune cells in atherosclerosis. A hallmark of atherosclerosis is the accumulation of pro-inflammatory macrophages in coronary arteries that respond to pro-atherogenic stimuli and failure of digesting lipids that contribute to foam cell formation in atherosclerotic plaques. This review illustrates the role of tryptophan-derived microbiota metabolites as an aryl hydrocarbon receptor (AhR) ligand that has immunomodulatory properties. Also, microbiota-dependent trimethylamine-N-oxide (TMAO) metabolite production is associated with a deleterious effect that promotes atherosclerosis, and metabolite indoxyl sulfate has been shown to exacerbate atherosclerosis. Our objective in this review is to discuss the role of microbiota-derived metabolites in atherosclerosis, specifically the consequences of microbiota-induced effects of innate immunity in response to atherogenic stimuli, and how specific beneficial/detrimental metabolites impact the development of atherosclerosis by regulating chronic endotoxemic and lipotoxic inflammation.


Assuntos
Aterosclerose , Células Espumosas , Microbioma Gastrointestinal/imunologia , Indicã , Metilaminas , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Aterosclerose/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Espumosas/imunologia , Células Espumosas/metabolismo , Células Espumosas/patologia , Humanos , Indicã/imunologia , Indicã/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Metilaminas/imunologia , Metilaminas/metabolismo , Receptores de Hidrocarboneto Arílico/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo
4.
PLoS One ; 15(12): e0242543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326419

RESUMO

Clinical studies using a range of omega-3 supplements have yielded conflicting results on their efficacy to control inflammation. Omega-3 fatty acids are substrate for the formation of potent immune-protective mediators, termed as specialized pro-resolving mediators (SPM). Herein, we investigated whether observed differences in the potencies of distinct omega-3 supplements were linked with their ability to upregulate SPM formation. Using lipid mediator profiling we found that four commercially available supplements conferred a unique SPM signature profile to human macrophages, with the overall increases in SPM concentrations being different between the four supplements. These increases in SPM concentrations were linked with an upregulation of macrophage phagocytosis and a decreased uptake of oxidized low-density lipoproteins. Pharmacological inhibition of two key SPM biosynthetic enzymes 5-Lipoxygenase or 15-Lipoxygenase reversed the macrophage-directed actions of each of the omega-3 supplements. Furthermore, administration of the two supplements that most potently upregulated macrophage SPM formation and reprogrammed their responses in vitro, to APOE-/- mice fed a western diet, increased plasma SPM concentrations and reduced vascular inflammation. Together these findings support the utility of SPM as potential prognostic markers in determining the utility of a given supplement to regulate macrophage responses and inflammation.


Assuntos
Aterosclerose/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Leucotrienos/biossíntese , Lipoxinas/biossíntese , Macrófagos/efeitos dos fármacos , Prostaglandinas/biossíntese , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Apolipoproteínas E/imunologia , Araquidonato 15-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/imunologia , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/imunologia , Aterosclerose/etiologia , Aterosclerose/imunologia , Aterosclerose/metabolismo , Dieta Ocidental/efeitos adversos , Ácidos Graxos Ômega-3/metabolismo , Feminino , Expressão Gênica , Humanos , Leucotrienos/imunologia , Lipoproteínas LDL/antagonistas & inibidores , Lipoproteínas LDL/farmacologia , Lipoxinas/imunologia , Inibidores de Lipoxigenase/farmacologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Knockout para ApoE , Fagocitose/efeitos dos fármacos , Cultura Primária de Células , Análise de Componente Principal , Prostaglandinas/imunologia
5.
Int J Mol Sci ; 21(24)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317034

RESUMO

Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people who have diabetes, the disease mentioned above constitutes together with stroke a severe social and economic burden. In diabetic patients after an ischemic stroke, an exorbitant activation of inflammatory molecular pathways and ongoing inflammation is responsible for more severe brain injury and impairment, promoting the advancement of ischemic stroke and diabetes. Considering that the ominous prognosis of ischemic brain damage could by partially clarified by way of already known risk factors the auspice would be modifying poor outcome in the post-stroke phase detecting novel biomolecules associated with poor prognosis and targeting them for revolutionary therapeutic strategies.


Assuntos
Aterosclerose/imunologia , /imunologia , Animais , Aterosclerose/complicações , Aterosclerose/genética , Barreira Hematoencefálica/metabolismo , Humanos , Imunidade Inata , Inflamassomos/genética , Inflamassomos/metabolismo , /genética , MicroRNAs/genética , MicroRNAs/metabolismo
6.
Medicine (Baltimore) ; 99(38): e22214, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957357

RESUMO

Anti-thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, enhances proinflammatory cytokine responses. Since low-grade inflammation is a known risk factor for atherosclerosis, a normal range of TPO-Ab (TPO-Ab negative) could be positively associated with atherosclerosis among participants with normal thyroid function. However, no study reported the association between normal range of TPO-Ab and atherosclerosis among eu-thyroid participants. A cross-sectional study was conducted with 1165 Japanese individuals with normal thyroid function (ie, normal range of free triiodothyronine [free T3] and free thyroxine [free T4]), aged 40 to 74 years, who participated in an annual health checkup in 2014. Among the study population, 115 were diagnosed as having atherosclerosis. A normal range value of TPO-Ab titer is revealed to be positively associated with atherosclerosis; sex, age, thyroid function (free T3 and thyroid-stimulating hormone), and known cardiovascular risk factor adjusted odds ratio and 95% confidence interval of atherosclerosis for logarithmic values of TPO-Ab was 2.23 (1.11, 4.47). When we limited the analysis to participants with normal levels of thyroid-stimulating hormone, this association became slightly stronger (2.65 [1.27,5.51]). Among the eu-thyroid general population, a normal range of TPO-Ab titer is revealed to be positively associated with atherosclerosis. Even though a TPO-Ab titer is not clinically relevant and is not associated with autoimmune thyroid disease, it could influence endothelial remodeling including atherosclerosis.


Assuntos
Aterosclerose/sangue , Autoanticorpos/sangue , Iodeto Peroxidase/imunologia , Idoso , Grupo com Ancestrais do Continente Asiático , Aterosclerose/imunologia , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tireotropina/sangue
7.
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
8.
Arterioscler Thromb Vasc Biol ; 40(9): 2070-2083, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32762445

RESUMO

OBJECTIVE: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar-/-/Apoe-/- mice were generated by cross-breeding of atherosclerosis-prone Apoe-/- mice and C3ar-/- mice. C3ar-/-/Apoe-/- mice and Apoe-/- mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b+ leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe-/- mice, C3ar-/-/Apoe-/- mice developed more severe atherosclerosis. In addition, C3ar-/-/Apoe-/- mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. CONCLUSIONS: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis-mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.


Assuntos
Aorta/metabolismo , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Inflamação/prevenção & controle , Macrófagos Peritoneais/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Aorta/imunologia , Aorta/patologia , Doenças da Aorta/imunologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiotaxia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , NF-kappa B/metabolismo , Fenótipo , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/deficiência , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Vascul Pharmacol ; 133-134: 106777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750408

RESUMO

Atherosclerosis is a systemic chronic inflammatory disease. Many antioxidants including alpha-lipoic acid (LA), a product of lipoic acid synthase (Lias), have proven to be effective for treatment of this disease. However, the question remains whether LA regulates the immune response as a protective mechanism against atherosclerosis. We initially investigated whether enhanced endogenous antioxidant can retard the development of atherosclerosis via immunomodulation. To explore the impact of enhanced endogenous antioxidant on the retardation of atherosclerosis via immune regulation, our laboratory has recently created a double mutant mouse model, using apolipoprotein E-deficient (Apoe-/-) mice crossbred with mice overexpressing lipoic acid synthase gene (LiasH/H), designated as LiasH/HApoe-/- mice. Their littermates, Lias+/+Apoe-/- mice, served as a control. Distinct redox environments between the two strains of mice have been established and they can be used to facilitate identification of antioxidant targets in the immune response. At 6 months of age, LiasH/HApoe-/- mice had profoundly decreased atherosclerotic lesion size in the aortic sinus compared to their Lias+/+Apoe-/- littermates, accompanied by significantly enhanced numbers of regulatory T cells (Tregs) and anti-oxidized LDL autoantibody in the vascular system, and reduced T cell infiltrates in aortic walls. Our results represent a novel exploration into an environment with increased endogenous antioxidant and its ability to alleviate atherosclerosis, likely through regulation of the immune response. These outcomes shed light on a new therapeutic strategy using antioxidants to lessen atherosclerosis.


Assuntos
Aorta/enzimologia , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Placa Aterosclerótica , Sulfurtransferases/biossíntese , Animais , Aorta/imunologia , Aorta/patologia , Doenças da Aorta/enzimologia , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aterosclerose/enzimologia , Aterosclerose/imunologia , Aterosclerose/patologia , Autoanticorpos/sangue , Modelos Animais de Doenças , Indução Enzimática , Lipoproteínas LDL/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Oxirredução , Estresse Oxidativo , Sulfurtransferases/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
11.
J Leukoc Biol ; 108(1): 297-308, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32531833

RESUMO

Monocytes and monocyte-derived cells, including Mϕs and dendritic cells, exhibit a diverse array of phenotypic states that are dictated by their surrounding microenvironment. These cells direct T cell activation and function via cues that range from being immunosuppressive to immunostimulatory. Solid tumors and atherosclerotic plaques represent two pathological niches with distinct immune microenvironments. While monocytes and their progeny possess a phenotypic spectrum found within both disease contexts, most within tumors are pro-tumoral and support evasion of host immune responses by tumor cells. In contrast, monocyte-derived cells within atherosclerotic plaques are usually pro-atherogenic, pro-inflammatory, and predominantly directed against self-antigens. Consequently, cancer immunotherapies strive to enhance the immune response against tumor antigens, whereas atherosclerosis treatments seek to dampen the immune response against lipid antigens. Insights into monocyte-T cell interactions within these niches could thus inform therapeutic strategies for two immunologically distinct diseases. Here, we review monocyte diversity, interactions between monocytes and T cells within tumor and plaque microenvironments, how certain therapies have leveraged these interactions, and novel strategies to assay such associations.


Assuntos
Aterosclerose/imunologia , Monócitos/imunologia , Neoplasias/imunologia , Linfócitos T/imunologia , Animais , Apresentação do Antígeno/imunologia , Comunicação Celular , Humanos
12.
PLoS Med ; 17(5): e1003115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379748

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association. METHODS AND FINDINGS: Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity. CONCLUSIONS: In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.


Assuntos
Imunidade Adaptativa/imunologia , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Imunidade Inata/imunologia , Idoso , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia
13.
Diabetes Metab Syndr ; 14(4): 713-714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470851

RESUMO

BACKGROUND AND AIMS: Older adults and people who have cardiovascular disorders (their common pathogenetic mechanism is progressive atherosclerosis) are at higher risk for severe illness from COVID-19 (coronavirus disease 2019). Their common pathogenetic mechanism is progressive atherosclerosis in which oxLDL (oxidized LDL) plays major role. Receptor-mediated uptake of oxLDL by the monocyte-derived macrophages activates the long-term epigenetic reprogramming of innate immunity, which is termed "trained immunity." The aim of this work is to investigate the mechanisms and treatment possibilities that can control the activities of these specific macrophages. METHODS: Search in Medline and PubMed relevant articles on the trained immunity and cytokine storm of COVID-19. RESULTS AND CONCLUSIONS: When oxLDL-trained macrophages encounter SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the lung, it causes unregulated cytokine secretion, leading to the alveolar damage. Therefore, blocking macrophage training by pioglitazone, a thiazolidinedione, could control the hyperactivation that the virus would trigger.


Assuntos
Aterosclerose/fisiopatologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Lipoproteínas LDL/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Pioglitazona/uso terapêutico , Pneumonia Viral/imunologia , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Humanos , Imunidade Inata , Mediadores da Inflamação , Pandemias , Pioglitazona/farmacologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Transdução de Sinais
14.
Circ Res ; 126(8): 1061-1085, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32271679

RESUMO

A central feature of atherosclerosis, the most prevalent chronic vascular disease and root cause of myocardial infarction and stroke, is leukocyte accumulation in the arterial wall. These crucial immune cells are produced in specialized niches in the bone marrow, where a complex cell network orchestrates their production and release. A growing body of clinical studies has documented a correlation between leukocyte numbers and cardiovascular disease risk. Understanding how leukocytes are produced and how they contribute to atherosclerosis and its complications is, therefore, critical to understanding and treating the disease. In this review, we focus on the key cells and products that regulate hematopoiesis under homeostatic conditions, during atherosclerosis and after myocardial infarction.


Assuntos
Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Hematopoese/fisiologia , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Doenças Cardiovasculares/imunologia , Endotélio Vascular/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia
15.
PLoS One ; 15(3): e0230358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32208424

RESUMO

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex α-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing α-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas α-2,6-sialylated ICAM-1 did not. Finally, both HM and α-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex α-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation.


Assuntos
Aterosclerose/patologia , Endotélio Vascular/patologia , Inflamação/patologia , Molécula 1 de Adesão Intercelular/imunologia , Isoformas de Proteínas/análise , Adulto , Idoso , Animais , Artérias/citologia , Artérias/patologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Aterosclerose/imunologia , Modelos Animais de Doenças , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Epitopos/análise , Epitopos/imunologia , Epitopos/metabolismo , Feminino , Glicosilação , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/imunologia , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/metabolismo , Macrófagos/imunologia , Masculino , Manose/metabolismo , Camundongos , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Ácido N-Acetilneuramínico/metabolismo , Isoformas de Proteínas/metabolismo , Adulto Jovem
16.
Arterioscler Thromb Vasc Biol ; 40(5): 1110-1122, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32131612

RESUMO

The immune system plays an important role in obesity-induced adipose tissue inflammation and the resultant metabolic dysfunction, which can lead to hypertension, dyslipidemia, and insulin resistance and their downstream sequelae of type 2 diabetes mellitus and cardiovascular disease. While macrophages are the most abundant immune cell type in adipose tissue, other immune cells are also present, such as B cells, which play important roles in regulating adipose tissue inflammation. This brief review will overview B-cell subsets, describe their localization in various adipose depots and summarize our knowledge about the function of these B-cell subsets in regulating adipose tissue inflammation, obesity-induced metabolic dysfunction and atherosclerosis.


Assuntos
Tecido Adiposo/imunologia , Aterosclerose/imunologia , Subpopulações de Linfócitos B/imunologia , Paniculite/imunologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Aterosclerose/terapia , Autoimunidade , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/patologia , Comunicação Celular , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Imunoterapia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Paniculite/diagnóstico , Paniculite/metabolismo , Paniculite/terapia , Fenótipo , Transdução de Sinais
17.
Lupus ; 29(3): 273-282, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32075511

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) patients experience a premature and more severe presentation of coronary artery disease. The underlying mechanisms of accelerated coronary artery disease in SLE patients remain to be elucidated. METHODS: By using atherosclerosis combining a SLE murine model, we proved that the onset of SLE aggravates atherosclerosis. Although the onset of SLE reduced blood lipids slightly, immune deviation contributed to aggravated atherosclerosis in lupus mice. Lupus atheroma were characterized by inflammatory cell infiltration, such as gathered dendritic cells, macrophages, and IgG deposition. RESULTS: Decreased lymphocytes and magnified dendritic cells in the spleen were also observed in lupus mice. Hydroxychloroquine prevented atherosclerosis progression mainly by reversing immune status abnormality caused by SLE. Serum interferon alfa levels were not changed in lupus mice. CONCLUSION: These findings strongly suggested that anti-inflammatory therapies and hydroxychloroquine provide a new possible strategy for treating SLE patients with atherosclerosis.


Assuntos
Aterosclerose/imunologia , Células Dendríticas/imunologia , Hidroxicloroquina/farmacologia , Imunoglobulina G/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos/imunologia , Animais , Aterosclerose/prevenção & controle , Células Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Feminino , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
18.
Arterioscler Thromb Vasc Biol ; 40(4): 865-873, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32078338

RESUMO

The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes. Therefore, noninvasive imaging of hematopoietic organs and immune cells will undoubtedly improve atherosclerosis phenotyping and serve as a monitoring method for immunotherapeutic treatments. Among the available imaging techniques, positron emission tomography's unique features make it an ideal tool to quantitatively image the immune response in the context of atherosclerosis and afford reliable readouts to guide medical interventions in cardiovascular disease. Here, we summarize the state of the art in the field of atherosclerosis positron emission tomography immunoimaging and provide an outlook on current and future applications.


Assuntos
Aterosclerose/diagnóstico por imagem , Aterosclerose/imunologia , Tomografia por Emissão de Pósitrons/métodos , Aterosclerose/metabolismo , Sistema Hematopoético/diagnóstico por imagem , Humanos , Nanopartículas , Fagócitos , Placa Aterosclerótica/diagnóstico por imagem , Radioimunodetecção , Compostos Radiofarmacêuticos
19.
Immunology ; 160(1): 10-23, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020584

RESUMO

Given the critical role that the immune system plays in a multitude of diseases, having a clear understanding of the pharmacology of the immune system is crucial to new drug discovery and development. Here we describe the International Union of Basic and Clinical Pharmacology (IUPHAR) Guide to Immunopharmacology (GtoImmuPdb), which connects expert-curated pharmacology with key immunological concepts and aims to put pharmacological data into the hands of immunologists. In the pursuit of new therapeutics, pharmacological databases are a vital resource to researchers through providing accurate information on the fundamental science underlying drug action. This extension to the existing IUPHAR/British Pharmacological Society Guide to Pharmacology supports research into the development of drugs targeted at modulating immune, inflammatory or infectious components of disease. To provide a deeper context for how the resource can support research we show data in GtoImmuPdb relating to a case study on the targeting of vascular inflammation.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Desenvolvimento de Medicamentos , Descoberta de Drogas , Sistema Imunitário/diagnóstico por imagem , Fatores Imunológicos/farmacologia , Alergia e Imunologia/educação , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Humanos , Fatores Imunológicos/uso terapêutico , Mediadores da Inflamação/metabolismo , Cooperação Internacional , Terapia de Alvo Molecular/métodos , Pesquisa Farmacêutica/educação , Farmacologia Clínica/educação , Ensaios Clínicos Controlados Aleatórios como Assunto , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Sociedades Científicas/organização & administração , Resultado do Tratamento
20.
Ecotoxicol Environ Saf ; 193: 110318, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32105945

RESUMO

The current study aimed to examine, for the first time, the relationship between exposure to deltamethrin (DLM) and atherogenic lipid profile disorders in adult Wistar rats, as well as, to verify the mechanism of the beneficial role of Zygophyllum album leaves extracts (ZALE). The experimental study was assessed using DLM (4 mg/kg b.w) either alone or co administered with ZALE (400 mg/kg b.w) orally for 90 days in rats. RP-HPLC-DAD-ESI-QTOF-MS was used to identify the bioactive metabolites present in ZALE. Plasmatic and aortic total cholesterol (TC), LDL-cholesterol (LDL-C), native LDL (LDL-apo B-100) and oxidized LDL (ox-LDL) were evaluated using auto-analyzer and a sandwich ELISA, respectively. The protein expressions of LDLR (native LDL receptor) and CD36 (Scavenger receptor class B) were evaluated in aorta or liver with a Western blot. The pathology has been confirmed with lipid stain (Oil Red O). Phytochemicals analysis revealed the presence of fifteen saponins in ZALE. Rats intoxicated with DLM revealed a significant increase in plasmatic and aortic lipid profile (TC, LDL-C, LDL-apo B-100 and ox-LDL), as well as, the concentration of the plasmatic cytokines include TNF-α, IL-2 and IL-6, compared to control. Hepatic native LDL and aortic CD36 receptor expression were increased in DLM treated group, however aortic LDL-R does not present any modification, when compared to control. The detected disturbances in lipid parameters were supported by Oil Red O applied. Due to their antioxidant activity, the bioactive compounds in ZALE as powerful agents able to prevent the pro-atherogenic effect observed in DLM-treated animals. These metabolites modulated most of inflammatory markers, prevented accumulation of lipid and lipoprotein biomarkers, regulated the major receptor regulators of hepatic cholesterol metabolism, as well as normalize lipid distribution in liver and aorta tissue.


Assuntos
Aorta/efeitos dos fármacos , Aterosclerose/prevenção & controle , Poluentes Ambientais/toxicidade , Lipoproteínas LDL/sangue , Nitrilos/toxicidade , Piretrinas/toxicidade , Saponinas/farmacologia , Zygophyllum/química , Animais , Aorta/imunologia , Aorta/metabolismo , Aterosclerose/imunologia , Aterosclerose/metabolismo , Antígenos CD36/metabolismo , Colesterol/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Masculino , Folhas de Planta/química , Ratos , Ratos Wistar , Receptores de LDL/metabolismo , Saponinas/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismo
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