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1.
Adv Exp Med Biol ; 1216: 55-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31894547

RESUMO

Chronic inflammation, which is called "inflamm-aging" , is characterized by an increased level of inflammatory cytokines in response to physiological and environmental stressors, and causes the immune system to function consistently at a low level, even though it is not effective. Possible causes of inflammaging include genetic susceptibility, visceral obesity, changes in gut microbiota and permeability, chronic infections and cellular senescence. Inflammation has a role in the development of many age-related diseases, such as frailty. Low grade chronic inflammation can also increase the risk of atherosclerosis and insulin resistance which are the leading mechanisms in the development of cardiovascular diseases (CVD). As it is well known that the risk of CVD is higher in older people with frailty and the risk of frailty is higher in patients with CVD, there may be relationship between inflammation and the development of CVD and frailty. Therefore, this important issue will be discussed in this chapter.


Assuntos
Doenças Cardiovasculares/complicações , Idoso Fragilizado , Fragilidade/complicações , Inflamação/complicações , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Envelhecimento/patologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Senescência Celular , Citocinas/imunologia , Fragilidade/imunologia , Fragilidade/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia
2.
J Sci Food Agric ; 100(2): 846-854, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31646650

RESUMO

BACKGROUND: Pomegranate has antioxidant, cardioprotective and anti-inflammatory properties. We designed a crossover study aimed at determining if consumption of pomegranate juice (PJ) improves lipid profile and oxidative and inflammatory biomarkers of hemodialysis patients. Forty-one hemodialysis patients were randomly assigned to one of two groups: PJ-treated group receiving 100 mL of natural PJ immediately after their dialysis session three times a week and the control group receiving the usual care. After 8 weeks, a 4-week washout period was established and then the role of the groups was exchanged. Lipid profile, blood pressure and oxidative and inflammatory biomarkers were measured before and after each sequence. RESULTS: Based on the results of intention-to-treat analysis, triglycerides were decreased in PJ condition and increased in the controls. Conversely, high-density lipoprotein cholesterol was increased in PJ and decreased in the control group. Total and low-density lipoprotein cholesterol did not significantly change in either condition. Systolic and diastolic blood pressure significantly decreased in PJ condition. Total antioxidant capacity increased in PJ condition (P < 0.001) and decreased in the controls (P < 0.001). Conversely, malondialdehyde and interleukin-6 decreased in PJ (P < 0.001) and increased in the control group (P ≤ 0.001). The changes of these biomarkers were significantly different between the two conditions. CONCLUSIONS: Eight-week PJ consumption showed beneficial effects on blood pressure, serum triglycerides, high-density lipoprotein cholesterol, oxidative stress and inflammation in hemodialysis patients. © 2019 Society of Chemical Industry.


Assuntos
Doenças Cardiovasculares/metabolismo , Sucos de Frutas e Vegetais/análise , Insuficiência Renal Crônica/dietoterapia , Adulto , Idoso , Pressão Sanguínea , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Estudos Cross-Over , Feminino , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Triglicerídeos/metabolismo
3.
Rev Cardiovasc Med ; 20(3): 153-160, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601089

RESUMO

Exosomes, nanosized lipid bilayer membranous vesicles, are secreted by a variety of cells and contain protein, lipids, mRNA, miRNA, and signaling molecules that participate in intercellular material transfer and information exchange through binding, fusion or endocytosis. Exosomes mediate the gene expression of target cells and regulate pathological and physiological processes, thereby playing a key role in the occurrence and development of various diseases. Accumulated studies has shown that exosomes hold therapeutic potential though their anti-apoptotic and anti-fibrotic roles. They also have been shown to promote angiogenesis, inhibit ventricular remodeling and improve cardiac function, as well as inhibiting local inflammation and regulating the immune response. As such, exosomes represent a new target for the treatment of cardiovascular diseases. This review summarizes the literature in this field to date, including the basic biological characteristics of exosomes, and new progress in the understanding of the mechanisms of their involvement in immune regulation in cardiovascular diseases. In this way, it servrs as a basis for future research and the development of therapeutic exosomes.


Assuntos
Doenças Cardiovasculares/imunologia , Sistema Cardiovascular/imunologia , Exossomos/imunologia , Sistema Imunitário/imunologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Exossomos/metabolismo , Exossomos/transplante , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Prognóstico , Transdução de Sinais
4.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480335

RESUMO

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function. Here, we present an updated review of the preclinical and clinical literature regarding the cardiotoxicity of COX inhibitors. While studies to date have focussed on the role of COX in influencing renal and vascular function, we suggest an interaction between prostanoids and T cells may be a novel factor, mediating elevated cardiovascular disease risk with NSAID use.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Inibidores de Ciclo-Oxigenase/efeitos adversos , Animais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Prostaglandinas/metabolismo , Fatores de Risco , Linfócitos T/efeitos dos fármacos
5.
Immunity ; 51(3): 508-521.e6, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31471109

RESUMO

Recent experimental data and clinical, genetic, and transcriptome evidence from patients converge to suggest a key role of interleukin-1ß (IL-1ß) in the pathogenesis of Kawasaki disease (KD). However, the molecular mechanisms involved in the development of cardiovascular lesions during KD vasculitis are still unknown. Here, we investigated intestinal barrier function in KD vasculitis and observed evidence of intestinal permeability and elevated circulating secretory immunoglobulin A (sIgA) in KD patients, as well as elevated sIgA and IgA deposition in vascular tissues in a mouse model of KD vasculitis. Targeting intestinal permeability corrected gut permeability, prevented IgA deposition and ameliorated cardiovascular pathology in the mouse model. Using genetic and pharmacologic inhibition of IL-1ß signaling, we demonstrate that IL-1ß lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Targeting mucosal barrier dysfunction and the IL-1ß pathway may also be applicable to other IgA-related diseases, including IgA vasculitis and IgA nephropathy.


Assuntos
Doenças Cardiovasculares/imunologia , Imunoglobulina A/imunologia , Inflamação/imunologia , Intestinos/imunologia , Animais , Modelos Animais de Doenças , Humanos , Interleucina-1beta/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Linfonodos Mucocutâneos/imunologia , Permeabilidade , Transdução de Sinais/imunologia , Vasculite/imunologia
6.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395800

RESUMO

The series of reactive biological events that we identify as inflammation has been investigated in recent years and unveiled as an important mechanism for regeneration. The study of the underlying complexity has been boosted by new technological innovation in research and allowed the identification of inflammatory responses as the basis of diseases that were considered degenerative rather than regenerative in nature. This is the case for cardiovascular diseases, from the organ damage that follows an acute event to the damage of target organs exposed to chronic risk factors. This editorial explores innovative aspects of inflammation in the setup of cardiovascular risk factors and diseases.


Assuntos
Doenças Cardiovasculares/etiologia , Inflamação/complicações , Animais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Citocinas/imunologia , Humanos , Inflamação/imunologia , Inflamação/terapia , NF-kappa B/imunologia , Fatores de Risco
7.
Int J Mol Sci ; 20(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200567

RESUMO

It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved.


Assuntos
Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Imunidade Inata/genética , Cromossomo Y/genética , Animais , Doenças Cardiovasculares/imunologia , Humanos
8.
Int J Mol Sci ; 20(10)2019 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31109146

RESUMO

Cardiovascular diseases are the leading cause of mortality worldwide. It is widely known that non-resolving inflammation results in atherosclerotic conditions, which are responsible for a host of downstream pathologies including thrombosis, myocardial infarction (MI), and neurovascular events. Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis. In this review we discuss the principles governing macrophage function in the healthy and infarcted heart. More specifically, how cardiac macrophages participate in myocardial infarction as well as cardiac repair and remodeling. The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. In the early "inflammatory" stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen. And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the "reparative/proliferative" phase. Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. Promising results demonstrate innovative concepts; one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient's post-MI diagnoses.


Assuntos
Doenças Cardiovasculares/imunologia , Imunidade Inata , Macrófagos/imunologia , Miocárdio/imunologia , Animais , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Coração/fisiopatologia , Humanos , Macrófagos/patologia , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Miocárdio/citologia , Miocárdio/patologia , Fatores de Proteção , Remodelação Ventricular
9.
Ther Adv Cardiovasc Dis ; 13: 1753944719851950, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31144599

RESUMO

Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient's reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women's health.


Assuntos
Doenças Cardiovasculares/imunologia , Depressão/imunologia , Sistema Imunitário/imunologia , Inflamação/imunologia , Reprodução/imunologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Depressão/metabolismo , Depressão/fisiopatologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Cinurenina/imunologia , Cinurenina/metabolismo , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Renina-Angiotensina/imunologia , Serotonina/imunologia , Serotonina/metabolismo , Transdução de Sinais
10.
J Nanobiotechnology ; 17(1): 72, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133024

RESUMO

BACKGROUND: Nano-sized vesicles, so called extracellular vesicles (EVs), from regenerative cardiac cells represent a promising new therapeutic approach to treat cardiovascular diseases. However, it is not yet sufficiently understood how cardiac-derived EVs facilitate their protective effects. Therefore, we investigated the immune modulating capabilities of EVs from human cardiac-derived adherent proliferating (CardAP) cells, which are a unique cell type with proven cardioprotective features. RESULTS: Differential centrifugation was used to isolate EVs from conditioned medium of unstimulated or cytokine-stimulated (IFNγ, TNFα, IL-1ß) CardAP cells. The derived EVs exhibited typical EV-enriched proteins, such as tetraspanins, and diameters mostly of exosomes (< 100 nm). The cytokine stimulation caused CardAP cells to release smaller EVs with a lower integrin ß1 surface expression, while the concentration between both CardAP-EV variants was unaffected. An exposure of either CardAP-EV variant to unstimulated human peripheral blood mononuclear cells (PBMCs) did not induce any T cell proliferation, which indicates a general low immunogenicity. In order to evaluate immune modulating properties, PBMC cultures were stimulated with either Phytohemagglutin or anti-CD3. The treatment of those PBMC cultures with either CardAP-EV variant led to a significant reduction of T cell proliferation, pro-inflammatory cytokine release (IFNγ, TNFα) and increased levels of active TGFß. Further investigations identified CD14+ cells as major recipient cell subset of CardAP-EVs. This interaction caused a significant lower surface expression of HLA-DR, CD86, and increased expression levels of CD206 and PD-L1. Additionally, EV-primed CD14+ cells released significantly more IL-1RA. Notably, CardAP-EVs failed to modulate anti-CD3 triggered T cell proliferation and pro-inflammatory cytokine release in monocultures of purified CD3+ T cells. Subsequently, the immunosuppressive feature of CardAP-EVs was restored when anti-CD3 stimulated purified CD3+ T cells were co-cultured with EV-primed CD14+ cells. Beside attenuated T cell proliferation, those cultures also exhibited a significant increased proportion of regulatory T cells. CONCLUSIONS: CardAP-EVs have useful characteristics that could contribute to enhanced regeneration in damaged cardiac tissue by limiting unwanted inflammatory processes. It was shown that the priming of CD14+ immune cells by CardAP-EVs towards a regulatory type is an essential step to attenuate significantly T cell proliferation and pro-inflammatory cytokine release in vitro.


Assuntos
Doenças Cardiovasculares/terapia , Vesículas Extracelulares/imunologia , Monócitos/imunologia , Miócitos Cardíacos/imunologia , Doenças Cardiovasculares/imunologia , Linhagem Celular , Proliferação de Células , Técnicas de Cocultura , Citocinas/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Imunomodulação , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Monócitos/citologia , Miócitos Cardíacos/citologia , Regeneração , Linfócitos T/citologia , Linfócitos T/imunologia
11.
Front Biosci (Landmark Ed) ; 24: 1462-1476, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136991

RESUMO

Preeclampsia is associated with an increased cardiovascular risk later in life. Anti-GPCR autoantibodies have been shown to contribute to the development of cardiovascular disease. We investigated whether anti-GPCR autoantibodies are elevated in women with a history of early-onset preeclampsia 8-11 years postpartum, and whether they correlate with clinical outcomes. We investigated data from the Preeclampsia Risk EValuation in FEMales cohort, a retrospective matched case-control study. Anti AT1R-, beta1AR-, ETAR-, PAR1- and CXCR3- autoantibodies were determined in 485 samples by using commercially available ELISA. Women with the lowest combined levels of autoantibodies and a history of early preeclampsia had significantly higher SBP, DBP and MAP (all p<0.001) compared to the controls. The individual titer levels of autoantibodies were not different between controls and former early PE groups 8-11 years postpartum. In conclusion, regulatory autoantibodies alone are not sufficient to explain hypertension or other cardiovascular pathologic conditions, but together with other risk factors such as a previous hypertensive pregnancy, lower levels of autoantibodies are associated with increased blood pressure.


Assuntos
Autoanticorpos/imunologia , Doenças Cardiovasculares/imunologia , Pré-Eclâmpsia/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Adulto , Autoanticorpos/sangue , Pressão Sanguínea/imunologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Pré-Eclâmpsia/fisiopatologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
13.
Biomed J ; 42(1): 27-35, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987702

RESUMO

A growing body of literature suggests that there is a link between periodontitis and systemic diseases. These diseases include cardiovascular disease, gastrointestinal and colorectal cancer, diabetes and insulin resistance, and Alzheimer's disease, as well as respiratory tract infection and adverse pregnancy outcomes. The presence of periodontal pathogens and their metabolic by-products in the mouth may in fact modulate the immune response beyond the oral cavity, thus promoting the development of systemic conditions. A cause-and-effect relationship has not been established yet for most of the diseases, and the mediators of the association are still being identified. A better understanding of the systemic effects of oral microorganisms will contribute to the goal of using the oral cavity to diagnose and possibly treat non-oral systemic disease.


Assuntos
Doenças Cardiovasculares/imunologia , Diabetes Mellitus/imunologia , Inflamação/imunologia , Periodontite/imunologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Fatores de Risco
14.
Ren Fail ; 41(1): 284-293, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31014150

RESUMO

OBJECTIVE: We investigate the mechanism of neutrophil/lymphocyte ratio (NLR) elevation, a useful prognostic marker in patients with cardiovascular diseases (CVDs). METHODS: In this clinical study, we retrospectively searched for factors associated with NLR elevation in cardiovascular outpatients. In animal experiments using mice with adenine-induced nephropathy, we further examined the hematopoietic process in bone marrow and explored the mechanism of NLR elevation. RESULT: In patients with CVDs or their risk factors, multiple regression analysis revealed that decrease in estimated glemerular filtration rate and increase in white blood cell count were significantly associated with increase in NLR. In mice with adenine-induced nephropathy, NLR and serum indoxyl sulfate (IS) levels were increased. Fluorescence-activated cell sorting revealed the increase in the number of myeloid progenitors and decrease in the number of common lymphoid progenitors, suggesting biased granulocyte side in the hematopoietic process in bone marrow. Treatment with oral charcoal adsorbent AST-120 decreased serum concentration of IS and normalized NLR and bone marrow abnormalities in mice with adenine-induced nephropathy. CONCLUSION: Renal function was a strong determinant of NLR in cardiovascular outpatients. NLR elevation due to renal impairment is caused by distortion of the hematopoietic process in bone marrow. IS plays a significant role in these processes.


Assuntos
Doenças Cardiovasculares/etiologia , Nefropatias/complicações , Linfócitos , Neutrófilos , Adenina/toxicidade , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Medula Óssea/patologia , Carbono/farmacologia , Carbono/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Modelos Animais de Doenças , Feminino , Taxa de Filtração Glomerular , Hematopoese/efeitos dos fármacos , Hematopoese/fisiologia , Humanos , Indicã/sangue , Indicã/metabolismo , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Óxidos/farmacologia , Óxidos/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco
15.
Immunity ; 50(4): 778-795, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995499

RESUMO

Forty years after its naming, interleukin-1 (IL-1) is experiencing a renaissance brought on by the growing understanding of its context-dependent roles and advances in the clinic. Recent studies have identified important roles for members of the IL-1 family-IL-18, IL-33, IL-36, IL-37, and IL-38-in inflammation and immunity. Here, we review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and their diversity and plasticity. We discuss the varied roles of IL-1 family members in immune homeostasis and their contribution to pathologies, including autoimmunity and auto-inflammation, dysmetabolism, cardiovascular disorders, and cancer. The trans-disease therapeutic activity of anti-IL-1 strategies argues for immunity and inflammation as a metanarrative of modern medicine.


Assuntos
Imunidade Adaptativa/imunologia , Citocinas/fisiologia , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-1/fisiologia , Animais , Doenças Cardiovasculares/imunologia , Citocinas/genética , Citocinas/imunologia , Gastroenteropatias/imunologia , Hematopoese/imunologia , Humanos , Interleucina-1/imunologia , Linfócitos/imunologia , Camundongos , Camundongos Knockout , Família Multigênica , Neoplasias/imunologia , Doenças Neurodegenerativas/imunologia , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia
16.
Immunity ; 50(4): 941-954, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995508

RESUMO

Arterial inflammation is a hallmark of atherosclerosis, and appropriate management of this inflammation represents a major unmet therapeutic need for cardiovascular disease patients. Here, we review the diverse contributions of immune cells to atherosclerosis, the mechanisms of immune cell activation in this context, and the cytokine circuits that underlie disease progression. We discuss the recent application of these insights in the form of immunotherapy to treat cardiovascular disease and highlight how studies on the cardiovascular co-morbidity that arises in autoimmunity might reveal additional roles for cytokines in atherosclerosis. Currently, data point to interleukin-1ß (IL-1ß), tumor necrosis factor (TNF), and IL-17 as cytokines that, at least in some settings, are effective targets to reduce cardiovascular disease progression.


Assuntos
Doenças Cardiovasculares/imunologia , Citocinas/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Cardiovasculares/tratamento farmacológico , Colesterol/metabolismo , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Citocinas/uso terapêutico , Progressão da Doença , Células Espumosas/imunologia , Células Espumosas/metabolismo , Microbioma Gastrointestinal , Humanos , Inflamassomos/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-1beta/antagonistas & inibidores , Camundongos Knockout , Modelos Imunológicos , Músculo Liso Vascular/imunologia , Fagócitos/imunologia , Fagócitos/metabolismo , Transdução de Sinais , Suínos , Pesquisa Médica Translacional
17.
Nat Rev Drug Discov ; 18(7): 553-566, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30967658

RESUMO

Immunotherapy is revolutionizing the treatment of diseases in which dysregulated immune responses have an important role. However, most of the immunotherapy strategies currently being developed engage the adaptive immune system. In the past decade, both myeloid (monocytes, macrophages and dendritic cells) and lymphoid (natural killer cells and innate lymphoid cells) cell populations of the innate immune system have been shown to display long-term changes in their functional programme through metabolic and epigenetic programming. Such reprogramming causes these cells to be either hyperresponsive or hyporesponsive, resulting in a changed immune response to secondary stimuli. This de facto innate immune memory, which has been termed 'trained immunity', provides a powerful 'targeting framework' to regulate the delicate balance of immune homeostasis, priming, training and tolerance. In this Opinion article, we set out our vision of how to target innate immune cells and regulate trained immunity to achieve long-term therapeutic benefits in a range of immune-related diseases. These include conditions characterized by excessive trained immunity, such as inflammatory and autoimmune disorders, allergies and cardiovascular disease and conditions driven by defective trained immunity, such as cancer and certain infections.


Assuntos
Epigênese Genética , Imunidade Inata/imunologia , Memória Imunológica/genética , Imunoterapia/métodos , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Humanos , Imunidade Inata/genética , /terapia , Neoplasias/imunologia , Neoplasias/terapia
18.
Nutr Metab Cardiovasc Dis ; 29(6): 604-610, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30952572

RESUMO

AIM: To evaluate the possible association between dietary habits and progenitor cells using data obtained from a randomized crossover trial using two different diets, lacto-ovo-vegetarian (VD) and Mediterranean (MD), the CARDIVEG study. METHODS AND RESULTS: Eighty clinically healthy subjects with a low-to-moderate cardiovascular risk profile (61 F; 19 M; mean age: 50.7 ± 11.6 years) were randomly assigned to isocaloric VD and MD diets lasting three months each, and then crossed. The two diets showed no effects on endothelial progenitor cells and circulating endothelial cells but opposite effects on circulating progenitor cells. In fact, VD determined significant (p < 0.05) and negative changes on circulating progenitor cells, with an average geometric variation of -130 cells/106 events for CD34+/CD45-/dim, -80 cells/106 events for CD133+/CD45-/dim, and -84 cells/106 events for CD34+/CD133+/CD45-/dim while MD determined significant (p < 0.05) and positive changes for CD34+/CD45-/dim levels, with a geometric mean increase of +54 cells/106 events. No significant correlations were observed between changes in progenitor cells and changes in inflammatory parameters during the VD phase. On the other hand, during the MD phase negative correlations between changes of CD34+/CD45-/dim and interleukin-6 (R = -0.324; p = 0.004) as well as interleukin-8 (R = -0.228; p = 0.04) and monocyte chemotactic protein-1 (R = -0.277; p = 0.01), were observed. These correlations remained significant also after adjustment for confounding factors only for CD34+/CD45-/dim and interleukin-6 (ß = -0.282; p = 0.018) and monocyte chemotactic protein-1 (ß = -0.254; p = 0.031). CONCLUSIONS: MD, but not VD, reported a significant and positive effect on circulating progenitor cells in a group of subjects at low-to-moderate cardiovascular risk, probably acting through the modulation of inflammatory parameters.


Assuntos
Antígenos CD/sangue , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Dieta Vegetariana , Mediadores da Inflamação/sangue , Prevenção Primária/métodos , Células-Tronco/metabolismo , Antígeno AC133/sangue , Adulto , Idoso , Antígenos CD34/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/imunologia , Quimiocina CCL2/sangue , Estudos Cross-Over , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Antígenos Comuns de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
19.
Am J Med ; 132(3): 312-324, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832770

RESUMO

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1ß) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1ß inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Interleucina-1beta/antagonistas & inibidores , Síndrome Metabólica/tratamento farmacológico , Neoplasias/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Humanos , Síndrome Metabólica/imunologia , Neoplasias/imunologia , Neoplasias/prevenção & controle , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/imunologia
20.
Int J Mol Sci ; 20(6)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897827

RESUMO

Periodontitis is a chronic inflammatory disease, initiated by the presence of a bacterial biofilm, called dental plaque, which affects both the periodontal ligaments and bone surrounding teeth. In the last decades, several lines of evidence have supported the existence of a relationship between periodontitis and systemic health. For instance, as periodontitis acts within the same chronic inflammatory model seen in cardiovascular disease (CVD), or other disorders, such as diabetes, several studies have suggested the existence of a bi-directional link between periodontal health and these pathologies. For instance, people with diabetes are more susceptible to infections and are more likely to suffer from periodontitis than people without this syndrome. Analogously, it is now evident that cardiac disorders are worsened by periodontitis, both experimentally and in humans. For all these reasons, it is very plausible that preventing periodontitis has an impact on the onset or progression of CVD and diabetes. On these grounds, in this review, we have provided an updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes, informing readers on the most recent preclinical studies and epidemiological evidence.


Assuntos
Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/metabolismo , Inflamação/metabolismo , Doenças Periodontais/metabolismo , Animais , Doenças Cardiovasculares/imunologia , Diabetes Mellitus/imunologia , Humanos , Inflamação/imunologia , Doenças Periodontais/imunologia , Fatores de Risco
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