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1.
Rev Med Suisse ; 15(672): 2159-2163, 2019 Nov 20.
Artigo em Francês | MEDLINE | ID: mdl-31746573

RESUMO

The main aims of the CoLaus/PsyCoLaus cohort study are to better understand: 1) the personal, biologic, genetic end environmental determinants of cardiovascular risk factors and diseases, and 2) the existing association of mental disorders with cardiovascular diseases. The study was initiated in 2003 and over 6700 participants from the city of Lausanne were include and very rich phenotypic data were collected making the study unique worldwide. Numerous scientific articles were published in various fields such as epidemiology, public health, genetic, social and environmental determinants of cardiovascular diseases and their association with mental health. We briefly present here some key results obtained over the last 16 years.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Transtornos Mentais/complicações , Doenças Cardiovasculares/epidemiologia , Seguimentos , Humanos , Transtornos Mentais/epidemiologia , Fatores de Risco , Suíça/epidemiologia
2.
J Clin Pathol ; 72(12): 785-799, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611285

RESUMO

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.


Assuntos
Líquidos Corporais/metabolismo , Doenças Cardiovasculares/diagnóstico , Técnicas de Diagnóstico Molecular , Medicina de Precisão , Biomarcadores/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Ácidos Nucleicos Livres/sangue , Tomada de Decisão Clínica , Humanos , Biópsia Líquida , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
3.
Medicine (Baltimore) ; 98(39): e17298, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574854

RESUMO

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2 , Haptoglobinas , Adulto , Biomarcadores/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Haptoglobinas/análise , Haptoglobinas/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
4.
J Agric Food Chem ; 67(44): 12191-12198, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588747

RESUMO

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Alho/química , Extratos Vegetais/administração & dosagem , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Espectrometria de Massas , Metabolômica , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
5.
Nat Med ; 25(9): 1390-1395, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501611

RESUMO

Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease1-3, as well as all-cause, cardiovascular-specific and cancer-specific mortality4,5. Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk of hypertension, heart attack/angina, type 2 diabetes and hyperlipidemia, and Mendelian randomization analysis showed visceral fat to be a causal risk factor for all four diseases. In particular, a large difference in causal effect between the sexes was found for type 2 diabetes, with an odds ratio of 7.34 (95% CI = 4.48-12.0) in females and an odds ratio of 2.50 (95% CI = 1.98-3.14) in males. Our findings bolster the role of visceral adiposity as a potentially independent risk factor, in particular for type 2 diabetes in Caucasian females. Independent validation in other cohorts is necessary to determine whether the findings can translate to other ethnicities, or outside the UK.


Assuntos
Adiposidade/genética , Doenças Cardiovasculares/genética , Gordura Intra-Abdominal/metabolismo , Doenças Metabólicas/genética , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/patologia , Gordura Intra-Abdominal/patologia , Masculino , Análise da Randomização Mendeliana , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/patologia , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais
6.
Nihon Yakurigaku Zasshi ; 154(2): 56-60, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406043

RESUMO

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand activated transcription factor known to regulate fatty acid metabolism. Thiazolidinediones (TZDs), PPARγ synthetic agonists, currently used to treat patients with type 2 diabetes, have been shown to lower the blood pressure and protect against vascular diseases such as atherosclerosis. In line with these findings, it has been reported that individuals with loss-of-function mutations of PPARγ developed sever early-onset hypertension in addition to metabolic abnormalities. Accumulating evidences suggest PPARγ in the vasculature has protective effects on cardiovascular disease despite unclear mechanism. Because of ubiquitous expression of PPARγ, TZDs are well-known to be associated with serious side effects such as weight gain, fluid retention, and bone fractures. Thus identification of mechanisms on tissue-specific PPARγ activity may lead to the development of targeted treatment which is characterized by no deleterious effects. This review discusses role of PPARγ in cardiovascular disease.


Assuntos
Doenças Cardiovasculares/genética , PPAR gama/genética , Tiazolidinedionas/farmacologia , Fatores de Transcrição/genética , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , PPAR gama/agonistas
7.
Curr Top Med Chem ; 19(21): 1918-1947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393249

RESUMO

microRNAs (miRNAs) are an evolutionarily conserved class of small single-stranded noncoding RNAs. The aberrant expression of specific miRNAs has been implicated in the development and progression of diverse cardiovascular diseases. For many decades, miRNA therapeutics has flourished, taking advantage of the fact that miRNAs can modulate gene expression and control cellular phenotypes at the posttranscriptional level. Genetic replacement or knockdown of target miRNAs by chemical molecules, referred to as miRNA mimics or inhibitors, has been used to reverse their abnormal expression as well as their adverse biological effects in vitro and in vivo in an effort to fully implement the therapeutic potential of miRNA-targeting treatment. However, the limitations of the chemical structure and delivery systems are hindering progress towards clinical translation. Here, we focus on the regulatory mechanisms and therapeutic trials of several representative miRNAs in the context of specific cardiovascular diseases; from this basic perspective, we evaluate chemical modifications and delivery vectors of miRNA-based chemical molecules and consider the underlying challenges of miRNA therapeutics as well as the clinical perspectives on their applications.


Assuntos
Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Bibliotecas de Moléculas Pequenas/química
8.
Adv Exp Med Biol ; 1193: 53-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368097

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a non-cytochrome P450 mitochondrial aldehyde oxidizing enzyme. It is best known for its role in the metabolism of acetaldehyde, a common metabolite from alcohol drinking. More evidences have been accumulated in recent years to indicate a greater role of ALDH2 in the metabolism of other endogenous and exogenous aldehydes, especially lipid peroxidation-derived reactive aldehyde under oxidative stress. Many cardiovascular diseases are associated with oxidative stress and mitochondria dysfunction. Considering that an estimated 560 million East Asians carry a common ALDH2 deficient variant which causes the well-known alcohol flushing syndrome due to acetaldehyde accumulation, the importance of understanding the role of ALDH2 in these diseases should be highlighted. There are several unfavorable cardiovascular conditions that are associated with ALDH2 deficiency. This chapter reviews the function of ALDH2 in various pathological conditions of the heart in relation to aldehyde toxicity. It also highlights the importance and clinical implications of interaction between ALDH2 deficiency and alcohol drinking on cardiovascular disease among the East Asians.


Assuntos
Acetaldeído/efeitos adversos , Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Doenças Cardiovasculares/genética , Grupo com Ancestrais do Continente Asiático , Humanos
9.
DNA Cell Biol ; 38(10): 1030-1039, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368785

RESUMO

Both endogenous and exogenous factors can cause DNA damage that compromises genomic integrity and cell viability. A proper DNA damage response (DDR) plays a role in maintaining genome stability and preventing tumorigenesis. DNA double-strand breaks (DSBs) are the most toxic DNA lesion, whose response is dominated by the ataxia-telangiectasia mutated (ATM) protein kinase. After being activated by the sensor Mre11-Rad50-Nbs1 (MRN) complex or acetyltransferase Tip60, ATM rapidly phosphorylates downstream targets to launch DDR signaling when DNA is damaged. However, the exact mechanism of DDR is complex and ambiguous. Ufmylation, one type of ubiquitin-like modification, proceeds mainly through a three-step enzymatic reaction to help ubiquitin-fold modifier 1 (Ufm1), attach to substrates with ubiquitin-like modifier-activating enzyme 5 (Uba5), Ufm1-conjugating enzyme 1 (Ufc1) and Ufm1-specific ligase 1 (Ufl1). Although ubiquitination is essential to the DSBs response, the potential function of ufmylation in DDR is largely unknown. Herein, we review the relationship between ufmylation and DDR to elucidate the function and mechanism of ufmylation in DDR, which would reveal the pathogenesis of some diseases and provide new guidance to create a therapeutic method.


Assuntos
Doenças Cardiovasculares/metabolismo , Quebras de DNA de Cadeia Dupla , Neoplasias/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Esquizofrenia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Reparo do DNA , Genoma Humano , Instabilidade Genômica , Humanos , Neoplasias/genética , Neoplasias/patologia , Ligação Proteica , Proteínas/genética , Esquizofrenia/genética , Esquizofrenia/patologia , Transdução de Sinais , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
10.
High Blood Press Cardiovasc Prev ; 26(4): 321-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325087

RESUMO

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Telômero/metabolismo , Fatores Etários , Envelhecimento/genética , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Senescência Celular , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/fisiopatologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Telômero/genética , Telômero/patologia , Homeostase do Telômero , Encurtamento do Telômero , Fatores de Tempo
11.
Clin Biochem ; 73: 44-49, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31251897

RESUMO

BACKGROUND: Scavenger receptor class B type 1 (SR-BI) encoded by SCARB1 gene serves as a multifunctional HDL receptor, facilitating the uptake of cholesteryl esters from HDL to the liver. Recent studies have identified the association between the P376L missense mutation of the SCARB1 gene with increased serum HDL-Cholesterol level. However, the contribution of this variant to the development of cardiovascular disease (CVD) remains unclear. OBJECTIVE: We have investigated the association between the P376L polymorphism with the properties of HDL and CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: Six hundred and fifteen individuals who had a median follow-up period of 7 years were recruited as part of the MASHAD cohort. Anthropometric, biochemical parameters and HDL lipid peroxidation (HDLox) were assessed. Genotyping was performed using TaqMan-real-time-PCR based method. The association of P376L-rs74830766 with cardiovascular-risk-factors and CVD events were evaluated. RESULTS: Carriers of the P376L variant were significantly more likely than non-carriers to develop CVD using multivariate analyses adjusted for traditional CVD risk factors defined as: age, sex, BMI, presence of diabetes, or hypertension, positive smoking habit, and total cholesterol (OR: 3.75, 95%CI: 1.76-7.98, p = 0.001). In an adjusted model, there was a two fold increase in cardiovascular endpoints among individuals who were heterozygous for the P376L variant (hazard ratio, 2.08; 95% CI, 1.12-to 3.84, p = 0.02). Although there was no association between the presence of the P376L variant and HDL-C level, serum HDLox, measured as dysfunctional HDL, was 13% higher among carriers of the P376L variant than non-carriers. CONCLUSION: We have found that carriers of the P376L variant possessed higher HDLox and were at increased risk of CVD in a representative population-based cohort, as compared to non-carriers.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/metabolismo , Polimorfismo Genético , Receptores Depuradores Classe B/genética , Adulto , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , HDL-Colesterol/genética , Feminino , Seguimentos , Humanos , Peroxidação de Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Fatores de Risco , Receptores Depuradores Classe B/metabolismo
12.
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
13.
Cell Mol Life Sci ; 76(20): 3969-3985, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31218451

RESUMO

Cardiovascular diseases represent one of the most important health problems of developed countries. One of the main actors involved in the onset and development of cardiovascular diseases is the increased production of reactive oxygen species that, through lipid peroxidation, protein oxidation and DNA damage, induce oxidative stress and cell death. Basic and clinical research are ongoing to better understand the endogenous antioxidant mechanisms that counteract oxidative stress, which may allow to identify a possible therapeutic targeting/application in the field of stress-dependent cardiovascular pathologies. In this context, increasing attention is paid to the glutathione/glutathione-peroxidase and to the thioredoxin/thioredoxin-reductase systems, among the most potent endogenous antioxidative systems. These key enzymes, belonging to the selenoprotein family, have a well-established function in the regulation of the oxidative cell balance. The aim of the present review was to highlight the role of selenoproteins in cardiovascular diseases, introducing the emerging cardioprotective role of endoplasmic reticulum-resident members and in particular one of them, namely selenoprotein T or SELENOT. Accumulating evidence indicates that the dysfunction of different selenoproteins is involved in the susceptibility to oxidative stress and its associated cardiovascular alterations, such as congestive heart failure, coronary diseases, impaired cardiac structure and function. Some of them are under investigation as useful pathological biomarkers. In addition, SELENOT exhibited intriguing cardioprotective effects by reducing the cardiac ischemic damage, in terms of infarct size and performance. In conclusion, selenoproteins could represent valuable targets to treat and diagnose cardiovascular diseases secondary to oxidative stress, opening a new avenue in the field of related therapeutic strategies.


Assuntos
Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Peptídeos/uso terapêutico , Selenocisteína/metabolismo , Selenoproteínas/genética , Animais , Antioxidantes/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/terapia , Regulação da Expressão Gênica , Glutationa Peroxidase/metabolismo , Humanos , Terapia de Alvo Molecular/métodos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Selenoproteínas/agonistas , Selenoproteínas/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo
14.
Arch Endocrinol Metab ; 63(3): 215-221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31066762

RESUMO

OBJECTIVE: This study investigated the familial aggregation and heritability of markers of metabolic risk, physical activity, and physical fitness in nuclear families from Muzambinho (Minas Gerais, Brazil). SUBJECTS AND METHODS: The study included members of 139 families, comprising 97 fathers (aged 40 ± 7 years), 129 mothers (35 ± 6 years), 136 sons (12 ± 4 years), and 121 daughters (12 ± 5 years). Evaluated markers included (A) body mass index, waist circumference, glycemia, and cholesterolemia, as metabolic risk markers; (B) total weekly volume of physical activity, as a physical activity marker; and (C) relative muscle strength, as a physical fitness marker. Correlations between family members and heritability (h2) were estimated using the software S.A.G.E. RESULTS: Significant familial correlations were obtained between parents-offspring for glycemia and cholesterolemia (both ρ = 0.21, p < 0.05) and relative muscle strength (ρ = 0.23, p < 0.05), and between siblings for waist circumference, glycemia, total weekly volume of physical activity, and relative muscle strength (ρ variation 0.25 to 0.36, p < 0.05). Heritability values were significant for almost all variables (h2 variations: 20% to 57% for metabolic risk markers, 22% for the total weekly volume of physical activity, and 50% for relative muscle strength), except for waist circumference (h2 = 15%, p = 0.059). CONCLUSION: The presence of significant correlations between family members and/or significant heritability strengthens the possible genetic and/or common familial environment influence on metabolic risk markers, total weekly volume of physical activity, and relative muscle strength.


Assuntos
Exercício , Síndrome Metabólica/genética , Adolescente , Adulto , Biomarcadores , Composição Corporal , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Criança , Exercício/fisiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Força Muscular/fisiologia , Núcleo Familiar , Aptidão Física/fisiologia , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
15.
Life Sci ; 233: 116440, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047893

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Non-coding RNAs including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) have been reported to participate in pathological developments of CVDs through various mechanisms. Among them, the networks among lncRNAs/circRNAs, miRNAs, and mRNAs have recently attracted attention. Understanding the molecular mechanism could aid the discovery of therapeutic targets or strategies in CVDs including atherosclerosis, myocardial infarction (MI), hypertrophy, heart failure (HF) and cardiomyopathy. In this review, we summarize the latest research involving the lncRNA/circRNA-miRNA-mRNA axis in CVDs, with emphasis on the molecular mechanism.


Assuntos
Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA/genética , Animais , Humanos , Transdução de Sinais
16.
Cell Mol Life Sci ; 76(18): 3497-3514, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31089747

RESUMO

Accurate determination of microRNA expression levels is a prerequisite in using these small non-coding RNA molecules as novel biomarkers in disease diagnosis and prognosis. Quantitative PCR is the method of choice for measuring the expression levels of microRNAs. However, a major obstacle that affects the reliability of results is the lack of validated reference controls for data normalization. Various non-coding RNAs have previously been used as reference controls, but their use may lead to variations and lack of comparability of microRNA data among the studies. Despite the growing number of studies investigating microRNA profiles to discriminate between healthy and disease stages, robust reference controls for data normalization have so far not been established. In the present article, we provide an overview of different reference controls used in various diseases, and highlight the urgent need for the identification of suitable reference controls to produce reliable data. Our analysis shows, among others, that RNU6 is not an ideal normalizer in studies using patient material from different diseases. Finally, our article tries to disclose the challenges to find a reference control which is uniformly and stably expressed across all body tissues, fluids, and diseases.


Assuntos
MicroRNAs/metabolismo , Biomarcadores/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/patologia , Hepatite B/genética , Hepatite B/patologia , Humanos , MicroRNAs/sangue , Neoplasias/genética , Neoplasias/patologia , Prognóstico , RNA Nuclear Pequeno/sangue , RNA Nuclear Pequeno/metabolismo , Tuberculose/genética , Tuberculose/patologia
17.
Ter Arkh ; 91(1): 71-77, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090375

RESUMO

AIM: To evaluate the association of a complex of cardiovascular risk factors and genetic markers with the development of high albuminuria among patients with arterial hypertension in the population of Mountain Shoriya, taking into account ethnicity. MATERIALS AND METHODS: A clinical epidemiological study of a compactly residing population in remote areas of Mountain Shoria was carried out. 1409 people were examined [901 people - representatives of the indigenous nationality (Shorians), 508 people - representatives of non-indigenous nationality (90% of them are Caucasians)]. Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. To study the state of the kidneys, the concentration (the presence of elevated levels) of albumin (albuminuria) in the morning portion of urine by an immunoturbidimetric method was analyzed. Polymorphisms of genes ACE (I/D, rs4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using PCR. RESULTS: In the group of shors with arterial hypertension, high albuminuria was associated with polymorphisms of the ACE genes (OR=2.05), ADRA2B (OR=6.00), elevated triglyceride level (OR=2.86), decreased index of cholesterol of high density lipoproteins (OR=5.57) and increased index of low density lipoproteins (OR=2.49); in the new population - with polymorphisms of the AGTR1 genes (OR=8.66), ADRA2B (OR=6.53), MTHFR (OR=7.16), obesity (OR=2.72), and abdominal obesity (OR=3.14). CONCLUSION: The primary predictors determining the development of high albuminuria among patients with arterial hypertension in both ethnic groups were genetic ones. In addition to them, non-genetic risk factors also contributed to the development of this organ damage to the kidneys: age and lipid metabolism disorders in representatives of indigenous nationality; age and abdominal obesity in the examined patients non-indigenous nationality.


Assuntos
Albuminas/metabolismo , Albuminúria/etnologia , Doenças Cardiovasculares/genética , Grupos Étnicos/genética , Hipertensão/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Receptores Adrenérgicos alfa 2/genética , Albuminúria/genética , Doenças Cardiovasculares/etnologia , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Hipertensão/etnologia , Lipoproteínas HDL/metabolismo , Obesidade Abdominal/etnologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Fatores de Risco , Federação Russa/epidemiologia , Triglicerídeos/metabolismo
18.
Maturitas ; 124: 68-71, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097182

RESUMO

There is an ongoing misperception that women under 60 years of age are at low risk of cardiovascular disease (CVD). As there is an important variation in risk among women in this age group, we need to tailor risk assessment by using additional risk parameters during their life-course. For this, valuable tools are family risk, female-specific risk factors and inflammatory co-morbidities, which can be enriched by measuring the coronary artery calcium (CAC) score using computerized tomography. Depending on the results, we can readily adapt lifestyle advice and preventive treatment to every individual woman. Progress has been made in the recognition of stable and unstable manifestations of ischemic heart disease in middle-aged women. Whereas the traditional cardiovascular risk factors are involved in classic obstructive coronary disease, female-specific risk variables, inflammatory co-morbidities and psychosocial stress are also involved in other types of ischemic disease. We therefore need a more sex- and gender-sensitive way to look at women's cardiovascular health.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Inflamação/epidemiologia , Doenças Cardiovasculares/genética , Comorbidade , Feminino , Humanos , Estilo de Vida , Medição de Risco , Fatores de Risco , Fatores Sexuais , Estresse Psicológico/epidemiologia , Saúde da Mulher
19.
Methodist Debakey Cardiovasc J ; 15(1): 62-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049151

RESUMO

Cardiovascular disease is the leading cause of death worldwide, and elevated lipid levels is a major contributor. Gene delivery, which involves controlled transfer of nucleic acids into cells and tissues, has been widely used in research to study lipid metabolism and physiology. Several technologies have been developed to somatically overexpress, silence, or disrupt genes in animal models and have greatly advanced our knowledge of metabolism. This is particularly true with regard to the liver, which plays a central role in lipoprotein metabolism and is amenable to many delivery approaches. In addition to basic science applications, many of these delivery technologies have potential as gene therapies for both common and rare lipid disorders. This review discusses three major gene delivery technologies used in lipid research-including adeno-associated viral vector overexpression, antisense oligonucleotides and small interfering RNAs, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing system-and examines their potential therapeutic applications.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/terapia , Terapia Genética/métodos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Animais , Sistemas CRISPR-Cas , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Dependovirus/genética , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Edição de Genes/métodos , Terapia Genética/efeitos adversos , Vetores Genéticos , Humanos , Oligonucleotídeos Antissenso/genética , RNA Interferente Pequeno/genética , Terapêutica com RNAi/métodos , Resultado do Tratamento
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