RESUMO
PURPOSE OF REVIEW: In this review, we explore the intriguing and evolving connections between bacterial extracellular membrane nanovesicles (BEMNs) and atherosclerosis development, highlighting the evidence on molecular mechanisms by which BEMNs can promote the athero-inflammatory process that is central to the progression of atherosclerosis. RECENT FINDINGS: Atherosclerosis is a chronic inflammatory disease primarily driven by metabolic and lifestyle factors; however, some studies have suggested that bacterial infections may contribute to the development of both atherogenesis and inflammation in atherosclerotic lesions. In particular, the participation of BEMNs in atherosclerosis pathogenesis has attracted special attention. We provide some general insights into how the immune system responds to potential threats such as BEMNs during the development of atherosclerosis. A comprehensive understanding of contribution of BEMNs to atherosclerosis pathogenesis may lead to the development of targeted interventions for the prevention and treatment of the disease.
Assuntos
Aterosclerose , Vesículas Extracelulares , Aterosclerose/microbiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Humanos , Vesículas Extracelulares/metabolismo , Animais , Inflamação/metabolismo , Bactérias/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/metabolismoRESUMO
Diabetes is a chronic disorder with rapidly increasing prevalence that is a major global issue of our current era. There are two major types of diabetes. Polygenic forms of diabetes include type 1 diabetes (T1D) and type 2 diabetes (T2D) and its monogenic forms are maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM). There are no permanent therapeutic approaches for diabetes and current therapies rely on regular administration of various drugs or insulin injection. Recently, gene editing strategies have offered new promise for treating genetic disorders. Targeted genome editing is a fast-growing technology, recruiting programmable nucleases to specifically modify target genomic sequences. These targeted nucleases generate double-strand breaks at target regions in the genome, which induce cellular repair pathways including non-homologous end joining (NHEJ) and homology-directed repair (HDR). Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is a novel gene-editing system, permitting precise genome modification. CRISPR/Cas9 has great potential for various applications in diabetic research such as gene screening, generation of diabetic animal models and treatment. In this article, gene-editing strategies are summarized with a focus on the CRISPR/Cas9 approach in diabetes research.
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Sistemas CRISPR-Cas , Diabetes Mellitus Tipo 2 , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Edição de Genes , Reparo de DNA por Recombinação , Reparo do DNA por Junção de ExtremidadesRESUMO
Metastasis is a hallmark of cancer and is responsible for the largest number of cancer-related deaths. However, it remains poorly understood. Recently, evidence has accumulated pointing to the role of mitochondria in the metastatic spread of cancer cells. Mitochondria are dynamic organelles that have significant metabolic activity and are considered signaling centers with biosynthetic, bioenergetic, and signaling functions that control key biological pathways. Also, data were presented that mitochondria can influence all processes associated with oncogenesis, from malignant transformation to metastatic dissemination. The role of mitochondria in cancer progression/metastasis includes alteration of glycolysis, regulation of ROS, and suppression of intrinsic apoptosis. This review will summarize the current knowledge on the contribution of mitochondria to tumor cell invasion and dissemination and the possible mechanisms behind this. Mitochondrial-targeted therapeutic strategies to combat metastatic cancer will also be proposed.
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Mitocôndrias , Neoplasias , Humanos , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Metabolismo Energético , Carcinogênese/metabolismo , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologiaRESUMO
Antibiotics are an indispensable component of therapeutic strategies in the treatment of severe bacterial infections. Unfortunately, in addition to the emerging resistance of bacteria to antibiotics, side effects are an important problem with their use. Knowledge of the mechanisms underlying the development of side effects can make it possible to understand how it is possible to reduce their negative impact on the health of patients. One of the negative effects of antibiotics on the human organism is interference with homeostasis and the functioning of mitochondria. Side effects of antibiotics based on this influence require further study. Here we consider the mitochondria as a side target of antibiotics and the main strategies of antibiotics that cause mitochondrial dysfunction. Options are also considered on how to deal with this problem and even use it for good.
Assuntos
Antibacterianos , Mitocôndrias , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Animais , Homeostase/efeitos dos fármacosRESUMO
Inflammation and lipid metabolism are two deeply interconnected and reciprocally regulated major physiological processes [...].
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Inflamação , Metabolismo dos Lipídeos , Mitocôndrias , Humanos , Inflamação/metabolismo , Mitocôndrias/metabolismo , AnimaisRESUMO
The fight against neurodegenerative diseases is one of the key direction of modern medicine. Unfortunately, the difficulties in understanding the factors underlying the development of neurodegeneration hinder the development of breakthrough therapeutics that can stop or at least greatly slow down the progression of these diseases. In this review, it is considered the disruption of mitochondrial transport as one of the pathogenesis factors contributing to neurodegeneration using the examples of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Here, the mechanism of mitochondrial transport under normal conditions and the mechanisms of disturbances for the indicated diseases will be considered.
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Doença de Alzheimer , Doença de Huntington , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , MitocôndriasRESUMO
The main aim of the current study was to summarize the findings of available clinical studies to assess nano-curcumin's influence on COVID patients. A comprehensive online search was performed in Scopus, PubMed, ISI Web of Science, and Google Scholar until March 2022 to identify trials that investigated the effects of nano-curcumin in patients with COVID-19. Eight studies comprising 569 patients were included in this review. Compared with placebo, nano-curcumin had no significant effect on C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). However, gene expression of IL-6 and gene expression as well as secretion of interleukin-1 beta (IL-1ß) significantly decreased following nano-curcumin intervention. Nano-curcumin had beneficial effects on fever, cough, chills, myalgia, and olfactory and taste disturbances. The duration of hospitalization and mortality rate were significantly lower in the nano-curcumin group compared with the control group. Lymphocyte count was significantly increased after curcumin supplementation. Nano-curcumin also had favorable effects on O2 saturation, sputum, chest pain, wheeze, and dyspnea in patients with COVID-19. No major adverse effects were reported in response to nano-curcumin supplementation. In summary, the results of this systematic review of clinical trials suggested that nano-curcumin supplementation has beneficial effects on inflammation, respiratory function, disease manifestations, and complications in patients with COVID-19 viral infection.
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COVID-19 , Curcumina , Humanos , Curcumina/farmacologia , Interleucina-6 , Proteína C-Reativa/análise , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. OBJECTIVE: To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). METHOD: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. RESULTS: Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. CONCLUSION: Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.
Assuntos
Doenças Cardiovasculares , Insulinas , Humanos , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Quercetina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Metanálise como AssuntoRESUMO
Atherosclerosis is a major global health problem. Being a harbinger of a large number of cardiovascular diseases, it ultimately leads to morbidity and mortality. At the same time, effective measures for the prevention and treatment of atherosclerosis have not been developed, to date. All available therapeutic options have a number of limitations. To understand the mechanisms behind the triggering and development of atherosclerosis, a deeper understanding of molecular interactions is needed. Heat shock proteins are important for the normal functioning of cells, actively helping cells adapt to gradual changes in the environment and survive in deadly conditions. Moreover, multiple HSP families play various roles in the progression of cardiovascular disorders. Some heat shock proteins have been shown to have antiatherosclerotic effects, while the role of others remains unclear. In this review, we considered certain aspects of the antiatherosclerotic activity of a number of heat shock proteins.
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Aterosclerose , Doenças Cardiovasculares , Humanos , Proteínas de Choque Térmico/metabolismo , Aterosclerose/tratamento farmacológico , Proteínas de Choque Térmico HSP70/metabolismoRESUMO
Essential oils (EOs) are complex secondary metabolites identified in many plant species. Plant-derived EOs have been widely used in traditional medicine for centuries for their health-beneficial effects. Some EOs and their active ingredients have been reported to improve the cardiovascular system, in particular to provide an anti-atherosclerotic effect. The objective of this review is to highlight the recent research investigating the anti-inflammatory, anti-oxidative and lipid-lowering properties of plant-derived EOs and discuss their mechanisms of action. Also, recent clinical trials exploring anti-inflammatory and anti-oxidative activities of EOs are discussed. Future research on EOs has the potential to identify new bioactive compounds and invent new effective agents for treatment of atherosclerosis and related diseases such as diabetes, metabolic syndrome and obesity.
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Aterosclerose , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos de Plantas/farmacologia , Aterosclerose/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Atherosclerosis is the major cause of cardiovascular-disease-related death worldwide, resulting from the subendothelial accumulation of lipoprotein-derived cholesterol, ultimately leading to chronic inflammation and the formation of clinically significant atherosclerotic plaques. Oligosaccharides have been widely used in biomedical research and therapy, including tissue engineering, wound healing, and drug delivery. Moreover, oligosaccharides have been consumed by humans for centuries, and are cheap, and available in large amounts. Given the constantly increasing number of obesity, diabetes, and hyperlipidaemia cases, there is an urgent need for novel therapeutics that can economically and effectively slow the progression of atherosclerosis. In this review, we address the current state of knowledge in oligosaccharides research, and provide an update of the recent in vitro and in vivo experiments that precede clinical studies. The application of oligosaccharides could help to eliminate the residual risk after the application of other cholesterol-lowering medicines, and provide new therapeutic opportunities to reduce the associated burden of premature deaths because of atherosclerosis.
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Aterosclerose , Placa Aterosclerótica , Humanos , Aterosclerose/tratamento farmacológico , Colesterol , Inflamação , Oligossacarídeos/uso terapêuticoRESUMO
Cardiovascular diseases are one of the leading causes of death worldwide. The identification of new pathogenetic targets contributes to more efficient development of new types of drugs for the treatment of cardiovascular diseases. This review highlights the problem of mitochondrial dynamics disorders, in the context of cardiovascular diseases. A change in the normal function of mitochondrial dynamics proteins is one of the reasons for the development of the pathological state of cardiomyocytes. Based on this, therapeutic targeting of these proteins may be a promising strategy in the development of cardiac drugs. Here we will consider changes for each process of mitochondrial dynamics in cardiovascular diseases: fission and fusion of mitochondria, mitophagy, mitochondrial transport and biogenesis, and also analyze the prospects of the considered protein targets based on existing drug developments.
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Doenças Cardiovasculares , Doenças Mitocondriais , Humanos , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , MitofagiaRESUMO
The prevalence of multiple sclerosis and the complexity of its etiology and pathogenesis require further study of the factors underlying the progression of this disease. The prominent role of mitochondria in neurons makes this organelle a vulnerable target for CNS diseases. The purpose of this review is to consider the role of mitochondrial dysfunction in the pathogenesis of multiple sclerosis, as well as to propose new promising therapeutic strategies aimed at restoring mitochondrial function in multiple sclerosis.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/patologia , Mitocôndrias/patologia , Neurônios/metabolismoRESUMO
For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.
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Aterosclerose/tratamento farmacológico , Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/química , Serina-Treonina Quinases TOR/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Humanos , Transdução de SinaisRESUMO
Atherosclerosis is the cause of the development of serious cardiovascular disorders, leading to disability and death. Numerous processes are involved in the pathogenesis of atherosclerosis, including inflammation, endothelial dysfunction, oxidative stress, and lipid metabolism disorders. Reverse transport of cholesterol is a mechanism presumably underlying the atheroprotective effect of high-density lipoprotein. In this review, we examined disorders of cholesterol metabolism and their possible effect on atherogenesis. We paid special attention to the reverse transport of cholesterol. Transformed cholesterol metabolism results in dyslipidemia and early atherosclerosis. Reverse cholesterol transport is an endogenous mechanism by which cells export cholesterol and maintain homeostasis. It is known that one of the main factors leading to the formation of atherosclerotic plaques on the walls of blood vessels are multiple modifications of low-density lipoprotein, and the formation of foam cells following them.
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Aterosclerose/metabolismo , Transporte Biológico/fisiologia , Colesterol/metabolismo , Animais , Humanos , Placa Aterosclerótica/metabolismoRESUMO
Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal. Today, we know a lot about the pathogenesis of atherosclerosis. However, the main knowledge is that the disease is extremely complicated. The development of atherosclerosis is associated with more than one molecular mechanism, each making a significant contribution. These mechanisms include endothelial dysfunction, inflammation, mitochondrial dysfunction, oxidative stress, and lipid metabolism disorders. This complexity inevitably leads to difficulties in treatment and prevention. One of the possible therapeutic options for atherosclerosis and its consequences may be metformin, which has already proven itself in the treatment of diabetes. Both diabetes and atherosclerosis are complex metabolic diseases, the pathogenesis of which involves many different mechanisms, including those common to both diseases. This makes metformin a suitable candidate for investigating its efficacy in cardiovascular disease. In this review, we highlight aspects such as the mechanisms of action and targets of metformin, in addition to summarizing the available data from clinical trials on the effective reduction of cardiovascular risks.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Metformina , Aterosclerose/metabolismo , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Estresse OxidativoRESUMO
Diabetic cardiomyopathy (DCM) is defined as the presence in diabetic patients of abnormal cardiac structure and performance (such as left ventricular hypertrophy, fibrosis, and arrhythmia) in the absence of other cardiac risk factors (such as hypertension or coronary artery disease). Although the pathogenesis of DCM remains unclear currently, mitochondrial structural and functional dysfunctions are recognised as a central player in the DCM development. In this review, we focus on the role of mitochondrial dynamics, biogenesis and mitophagy, Ca2+ metabolism and bioenergetics in the DCM development and progression. Based on the crucial role of mitochondria in DCM, application of mitochondria-targeting therapies could be effective strategies to slow down the progression of the disease.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Diabetes Mellitus/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Coração , Humanos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , MitofagiaRESUMO
Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.
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Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Coração/fisiologia , Regulação da Expressão Gênica , Humanos , Transdução de SinaisRESUMO
Cardiovascular diseases (CVD) are one of the leading causes of morbidity and mortality worldwide. mtDNA (mitochondrial DNA) mutations are known to participate in the development and progression of some CVD. Moreover, specific types of mitochondria-mediated CVD have been discovered, such as MIEH (maternally inherited essential hypertension) and maternally inherited CHD (coronary heart disease). Maternally inherited mitochondrial CVD is caused by certain mutations in the mtDNA, which encode structural mitochondrial proteins and mitochondrial tRNA. In this review, we focus on recently identified mtDNA mutations associated with CVD (coronary artery disease and hypertension). Additionally, new data suggest the role of mtDNA mutations in Brugada syndrome and ischemic stroke, which before were considered only as a result of mutations in nuclear genes. Moreover, we discuss the molecular mechanisms of mtDNA involvement in the development of the disease.
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Doenças Cardiovasculares/genética , DNA Mitocondrial/genética , Mitocôndrias/genética , Mutação , Predisposição Genética para Doença , Humanos , Herança MaternaRESUMO
Several recent cardiovascular trials of SGLT 2 (sodium-glucose cotransporter 2) inhibitors revealed that they could reduce adverse cardiovascular events in patients with T2DM (type 2 diabetes mellitus). However, the exact molecular mechanism underlying the beneficial effects that SGLT2 inhibitors have on the cardiovascular system is still unknown. In this review, we focus on the molecular mechanisms of the mitochondria-mediated beneficial effects of SGLT2 inhibitors on the cardiovascular system. The application of SGLT2 inhibitors ameliorates mitochondrial dysfunction, dynamics, bioenergetics, and ion homeostasis and reduces the production of mitochondrial reactive oxygen species, which results in cardioprotective effects. Herein, we present a comprehensive overview of the impact of SGLT2 inhibitors on mitochondria and highlight the potential application of these medications to treat both T2DM and cardiovascular diseases.