Arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg: qual a diferença? / Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular.

Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Influence of height on endothelial maintenance activity: a narrative review

Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

Rol de los fitoestrógenos en la calcificación vascular e interacciones óseo-vasculares / Role of phytoestrogens in vascular calcification and bonevascular interactions

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

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

Evaluation of Myocardial Ischemia with iFR (Instantaneous Wave-Free Ratio in the Catheterization Laboratory: A Pilot Study / Avaliação de Isquemia Miocárdica na Sala de Hemodinâmica com iFR Instantaneous Wave-Free Ratio: Estudo Piloto

Abstract Background: The Instantaneous Wave-Free Ratio (iFR) is an invasive functional evaluation method that does not require vasoactive drugs to induce maximum hyperemia Objective: To evaluate the contribution of the iFR to the therapeutic decision-making of coronary lesions in the absence of non-invasive diagnostic methods for ischemia, or in case of discordance between these methods and coronary angiography. Method: We studied patients older than 18 years, of both sexes, consecutively referred for percutaneous treatment between May 2014 and March 2018. Coronary stenotic lesions were classified by visual estimation of the stenosis diameter into moderate (41-70% stenosis) or severe (71%-90%). An iFR ≤ 0.89 was considered positive for ischemia. Logistic regression was performed using the elastic net, with placement of stents as outcome variable, and age, sex, arterial hypertension, diabetes, dyslipidemia, smoking, family history, obesity and acute myocardial infarction (AMI) as independent variables. Classification trees, ROC curves, and Box Plot graphs were constructed using the R software. A p-value < 0.05 was considered statistically significant. Results: Fifty-two patients with 96 stenotic lesions (56 moderate, 40 severe) were evaluated. The iFR cut-off point of 0.87 showed a sensitivity of 0.57 and 1-specificity of 0.88, demonstrating high accuracy in reclassifying the lesions. Diabetes mellitus, dyslipidemia, and presence of moderate lesions with an iFR < 0.87 were predictors of stent implantation. Stents were used in 32% of lesions in patients with stable coronary artery disease and AMI with or without ST elevation (non-culprit lesions). Conclusion: The iFR has an additional value to the therapeutic decision making in moderate and severe coronary stenotic lesions, by contributing to the reclassification of lesions and decreasing the need for stenting.

Resumo Fundamento: Instantaneous Wave-Free Ratio (iFR) é um método de avaliação funcional invasiva sem necessidade de droga vasoativa para indução de hiperemia máxima. Objetivo: Analisar a contribuição do iFR na terapêutica das lesões coronarianas com ausência ou discrepância entre os métodos diagnósticos não invasivos para isquemia e a angiografia coronária. Método: Foram estudados pacientes consecutivos com 18 anos ou mais, ambos os sexos, no período de maio de 2014 a março de 2018, com lesões coronarianas classificadas, por medição da porcentagem de diâmetro da estenose através de estimativa visual, em estenoses moderadas (41-70%) ou graves (71%-90%). O iFR ≤ 0,89 foi considerado positivo para isquemia. Empregou-se regressão logística com elastic net, tendo como variável desfecho o emprego de stent, e variáveis independentes: idade, sexo, hipertensão arterial, diabetes, dislipidemia, tabagismo, história familiar, obesidade e infarto agudo do miocárdio (IAM) prévio. Foram construídas Árvores de Classificação, Curva Roc, e gráficos Box Plot com o software R. O valor de p < 0,05 foi considerado significativo. Resultados: Foram avaliados 52 pacientes com 96 lesões obstrutivas (56 moderadas, 40 graves). O ponto de corte do iFR de 0,87 apresentou sensibilidade de 0,57 e 1-especificidade de 0,88, demonstrando boa acurácia para a reclassificação das lesões. Diabetes mellitus, dislipidemia, e presença de lesão moderada, com iFR < 0,87 foram preditores do implante de stents. Foram empregados stents em 32% das lesões de portadores de doença arterial coronariana estável e IAM com e sem supra de ST (lesões não culpadas). Conclusão: O iFR contribui para a reclassificação das lesões e diminuição do emprego de stents, auxiliando na abordagem das lesões moderadas e severas.

Animal models of human atherosclerosis: current progress

Atherosclerosis retains the leading position among the causes of global morbidity and mortality worldwide, especially in the industrialized countries. Despite the continuing efforts to investigate disease pathogenesis and find the potential points of effective therapeutic intervention, our understanding of atherosclerosis mechanisms remains limited. This is partly due to the multifactorial nature of the disease pathogenesis, when several factors so different as altered lipid metabolism, increased oxidative stress, and chronic inflammation act together leading to the formation and progression of atherosclerotic plaques. Adequate animal models are currently indispensable for studying these processes and searching for novel therapies. Animal models based on rodents, such as mice and rats, and rabbits represent important tools for studying atherosclerosis. Currently, genetically modified animals allow for previously unknown possibilities in modelling the disease and its most relevant aspects. In this review, we describe the recent progress made in creating such models and discuss the most important findings obtained with them to date.

Efeitos dos picnogenol® na doença aterosclerótica crônica / Effects of picnogenol® on chronic atherosclerosis

A doença aterosclerótica crônica (DAC) é uma condição bastante prevalente em nosso meio e uma das principais doenças cardiovasculares ligadas ao envelhecimento. Dentre as opções terapêuticas adjuvantes, o Picnogenol ®, extrato da casca do Pinus pinaster, tem sido alvo de estudo em decorrência de função antioxidante, anti-inflamatória e antiplaquetária. Este artigo é uma revisão narrativa, cujo objetivo é avaliar o uso do Picnogenol® como opção terapêutica da DAC. Os estudos incluídos foram pesquisados nas bases de dados: PubMed, Scielo, The Cochrane Library, Scopus e LILACS, sendo excluídos, considerando suas restrições para avaliação terapêutica, os relatos de caso e séries de caso com n ≤ 5. Como resultado, os estudos têm apontado vantagens do uso Picnogenol® no tratamento da DAC, assim como de outras doenças cardiovasculares, porém, o número de pesquisas ainda é pequeno (principalmente ensaios clínicos) e há importantes limitações de tamanho amostral, o que dificulta sua atual recomendação na prática clínica

Chronic atherosclerosis is a highly prevalent condition and one of the main cardiovascular diseases linked to the aging process. Among the adjuvant therapeutic options, Pycnogenol® (Pinus pinaster bark extract) has been studied because of its antioxidant, anti-inflammatory and antiplatelet functions. This article is a narrative review aimed at evaluating the use of Pycnogenol® as a therapeutic option in the treatment of chronic atherosclerosis. The studies included were obtained from the following databases: PubMed, Scielo, The Cochrane Library, Scopus and LILACS. Case reports and case series with n≤5 were excluded due to their restrictions for therapeutic evaluation. As a result, the studies have indicated advantages in the use of Pycnogenol® in the treatment of chronic atherosclerosis as well as other cardiovascular diseases. However, the number of studies is still small (particularly clinical trials), and there are important sample size limitations, which restricts its current recommendation in clinical practice

Efecto del consumo de alimentos con elevado contenido lipídico sobre el perfil lipídico de ratones sanos / Effect of the consumption of foods with high lipid content on lipid profile of healthy mice

La alteración de los lípidos en sangre o dislipidemias sobre todo el colesterol y triglicéridos, son un factor de riesgo de ateroesclerosis y enfermedades cardiovasculares. En este trabajo se analizó el efecto del consumo de huevo, clara, yema de huevo, mantequilla y maní sobre el perfil lipídico de ratones sanos. Se utilizaron seis grupos de ratones hembras sanas, el grupo control (GC) recibió balanceado comercial, mientras que en los demás grupos, 15% de su alimentación diaria consistió en huevo entero (GHE), yema (GY), clara de huevo (GCH), manteca o mantequilla (GMT) o maní (GMN), durante 28 días. Al final de este periodo, se obtuvo la muestra de suero para la determinación de los niveles de colesterol total (CT), triglicéridos (TG), colesterol HDL, colesterol LDL y colesterol VLDL, y se calcularon los índices de riesgo aterogénico y de riesgo cardiaco. Se observó un aumento estadísticamente significativo en los niveles de CT y LDL en relación al GC en los grupos GHE (p<0,0001), GY (p<0,0001), GCH (p<0,005) y GMT (p<0,001), mientras que en niveles de TG presentan un aumento los grupos GHE (p<0,0001) y GY (p<0,0001). El nivel de HDL aumentó significativamente en los grupos GHE (p<0,005) y GMT (p<0,001), y en cuanto al índice de riesgo cardiaco y aterogénico el grupo GY fue el único que reveló aumento significativo (p<0,0001). En el grupo que recibió maní (GMN), no se alteraron los niveles de lípidos, y por lo tanto tampoco el riesgo cardiaco ni aterogénico, lo que se traduce en un menor riesgo de enfermedades cardiovasculares de este grupo(AU)

The alteration of blood lipids or dyslipidemias, especially cholesterol and triglycerides, are a risk factor for atherosclerosis and cardiovascular diseases. In this work, the effect of consumption of egg, egg white, egg yolk, butter and peanut on the lipid profile of healthy mice was analyzed. Six groups of healthy female mice were used, the control group (GC) received commercial pellets, while for the other groups, 15% of their daily food consisted of whole egg (GHE), egg yolk (GY), egg white (GCH) ), butter (GMT) or peanut (GMN), for 28 days. At the end of this period, a serum sample was obtained for the determination of the levels of total cholesterol (CT), triglycerides (TG), HDL cholesterol, LDL cholesterol and VLDL cholesterol, and cardiac and atherogenic risk index were calculated. A statistically significant increase in TC and LDL levels was observed in relation to GC in the GHE (p <0,0001), GY (p <0,0001), GCH (p <0,005) and GMT (p <0,001) groups; whereas TG levels showed an increase in the GHE (p <0,0001) and GY (p <0,0001) groups. The HDL level increased significantly in the groups GHE (p <0,005) and GMT (p <0,001), and in terms of the cardiac and atherogenic risk index, the GY group was the only group that revealed a significant increase (p <0,0001). In the group that received peanuts (GMN), the lipid levels were not altered, and therefore neither the cardiac nor the atherogenic risk, which indicates the risk of cardiovascular diseases in this group, were affected(AU)

An update on the tools for creating transgenic animal models of human diseases - focus on atherosclerosis

Animal models of diseases are invaluable tools of modern medicine. More than forty years have passed since the first successful experiments and the spectrum of available models, as well as the list of methods for creating them, have expanded dramatically. The major step forward in creating specific disease models was the development of gene editing techniques, which allowed for targeted modification of the animal's genome. In this review, we discuss the available tools for creating transgenic animal models, such as transgenesis methods, recombinases, and nucleases, including zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and CRISPR/Cas9 systems. We then focus specifically on the models of atherosclerosis, especially mouse models that greatly contributed to improving our understanding of the disease pathogenesis and we outline their characteristics and limitations.

Incidence of Cytomegalovirus Antigenemia in patients with autoimmune rheumatic diseases: a 3-year retrospective study

Abstract Objective: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. Methods: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. Results: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40. 9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ±55.4 mg vs. 71.7 ±46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/ mm3; p = 0.06). Conclusions: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.

Quando e como avaliar o risco cardiovascular global em indivíduos aparentemente normais ­ ou check-up para todos / When and how to assess global cardiovascular risk in apparently normal individuals ­ or check-up for everyone

A prevenção cardiovascular é tema fundamental, pois as doenças cardiovasculares que têm como substrato a aterosclerose, têm grande impacto na morbidade e mortalidade cardiovascular no Brasil e no mundo. Estima-se que 80% dos casos de doença arterial co-ronariana resultam da presença isolada ou em associação a fatores como as dislipidemias, tabagismo, hipertensão arterial, diabetes entre outros. Além disso, biomarcadores como história familiar de aterosclerose precoce, marcadores de inflamação de baixo grau como a proteína C reativa (PCR) e imagem da placa de ateroma (escore de cálcio coronário) ajudam a identificar e reclassificar o risco de doença cardiovascular. Estratégias como check-up cardiovascular ou os dos escores de risco são utilizadas na identificação do indivíduo assintomático com maior risco de desenvolver um evento agudo. O check-upcardiovascular, além de identificar os fatores de risco, inclui exames laboratoriais, testes funcionais e de imagem, o que pode implicar em custos excessivos dos exames que não agregarão valor discriminatório ou de reclassificação do risco cardiovascular. Apesar da escassez de dados, meta-análise recente não observou qualquer diferença na mortali-dade por todas as causas e cardiovascular, quanto à realização ou não dos exames de check-up de rotina. A partir da medicina baseada em evidência, diversos algoritmos foram criados para estratificação, de acordo com a presença dos fatores de risco e calibrados para a população estudada. Esses algoritmos são de simples realização e de baixo custo.A Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose ­ 2017 mantém a recomendação do uso do Escore Global de Risco na avalição inicial de indiví-duos assintomáticos. A revisão sistemática realizada pelo grupo Cochrane, observou que o uso dos escores de risco na prevenção primária tiveram modesto impacto na redução de eventos cardiovasculares, comparados com a não utilização. Além disso, o uso dos escores clínicos reduziu fatores de risco como colesterol elevado e hipertensão arterial, aumentou a prescrição de hipolipemiantes, anti-hipertensivos e AAS, sem evidência de danos e diminuiu a prevalência de tabagismo. Atualmente, ainda há controvérsias sobre quando e como deve ser feita a avaliação do risco cardiovascular. A literatura é clara em dizer que o uso de testes de forma indiscriminada na população não tem boa relação de custo-eficácia. Entretanto, a avaliação do risco cardiovascular pelos escores clínicos de risco pode identificar indivíduos de maior risco que serão beneficiados pela implementação de tratamentos preventivos.

Cardiovascular disease prevention is a key topic as cases with atherosclerosis as an underlying cause have a considerable impact on cardiovascular morbidity and mortality in Brazil and the rest of the world. It is estimated that 80% of coronary artery disease cases result from the individual presence or combination of factors such as dyslipidemias, smo-king, hypertension, diabetes, and others. In addition, biomarkers such as family history of early atherosclerosis, low-grade inflammatory markers such as C-reactive protein (CRP), and atheromatous plaque imaging (coronary calcium score) help identify and reclassify the risk of cardiovascular disease. Strategies such as cardiovascular check-ups or the use of risk scores are used to identify the asymptomatic patient with a higher risk of developing an acute event. Besides identifying risk factors, the cardiovascular check-up also includes laboratory, functional and imaging tests, which may involve excessive costs that will not add discriminatory value or allow the cardiovascular risk to be reclassified. Despite the lack of data, a recent meta-analysis found no difference in all-cause and cardiovascular mortality, whether or not routine check-ups were performed. According to evidence-based medicine, several algorithms have been created for stratification, depending on the presence of risk factors and calibrated for a particular study population. These algorithms are both simple and inexpensive. The Update of the Brazilian Guideline on Dyslipidemia and Atherosclerosis Prevention - 2017 recommends using the Global Risk Score in the initial assessment of asymptomatic individuals. A systematic review conducted by the Cochrane group found that the use of risk scores in primary prevention had a modest impact on the reduction of cardiovascular events compared to non-use. Furthermore, the use of clinical scores reduced risk factors such as high cholesterol and high blood pressure, increased lipid-lowering/antihypertensive drug and aspirin prescriptions, with no evidence of harmful side effects, and reduced the prevalence of smoking. There is still controversy as to when and how to assess cardiovascular risk. The literature is clear in stating that the use of indiscriminate testing in the population is not cost effective. However, the evaluation of cardiovascular risk using clinical risk scores can identify higher risk individuals who will benefit from the implementation of preventive treatments.

Role of miRNAs on the Pathophysiology of Cardiovascular Diseases / Papel dos miRNAs na Fisiopatologia das Doenças Cardiovasculares

Abstract MiRNA (or microRNA) is a subclass of non-coding RNAs that is responsible for post-transcriptional gene regulation. It has approximately 22 nucleotides and regulates gene expression in plants and animals at the post-transcriptional level, by the cleavage of a target mRNA or by suppression of its translation. Although many of the processes and mechanisms have not yet been fully elucidated, there is a strong association between miRNA expression and several diseases. It is known that miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases (CVDs) has not been clearly established. In this non-systematic review of the literature, we first present the definition of miRNAs and their action at the cellular level. Afterward, we discuss the role of miRNAs as circulating biomarkers of CVDs, and then their role in cardiac remodeling and atherosclerosis. Despite the complexity and challenges, it is crucial to identify deregulated miRNAs in CVDs, as it allows a better understanding of underlying cellular and molecular mechanisms and helps in the development of more accurate diagnostic and prognostic circulating biomarkers, and new therapeutic strategies for different stages of CVDs.

Resumo O miRNA (ou microRNA) constitui uma subclasse de RNAs não codificantes responsáveis pela regulação gênica pós-transcricional. Ele possui aproximadamente 22 nucleotídeos e regula a expressão gênica em plantas e animais ao nível pós-transcricional, pela clivagem de um mRNA alvo ou da repressão de sua tradução. Embora muitos processos e mecanismos ainda não estejam completamente elucidados, existe uma forte associação entre a expressão de miRNAs e diversas doenças que acometem o organismo. Os miRNAs são expressos no sistema cardiovascular, contudo o seu papel no desenvolvimento das doenças cardiovasculares (DCVs) ainda não está totalmente elucidado. Diante disso, realizou-se uma revisão não sistemática da literatura a fim de se discutir a relação entre os miRNAs e as DCVs. Nesta revisão, primeiramente é discutido o que são os miRNAs e a sua ação a nível celular. Após, é discutido o papel dos miRNAs como biomarcadores circulantes de DCVs e então o seu papel no remodelamento cardíaco e na aterosclerose. Apesar da complexidade e dos desafios, a identificação dos miRNAs desregulados nas DCVs é crucial, uma vez que possibilita uma melhor compressão dos mecanismos celulares e moleculares envolvidos, assim como auxilia o desenvolvimento de marcadores circulantes de diagnóstico e prognóstico mais acurados e de novas estratégias terapêuticas para os diferentes estágios da DCV.

Histological verification of atherosclerosis due to bends and bifurcations in carotid arteries predicted by hemodynamic model / Confirmação histológica de aterosclerose devido a dobras e bifurcações das artérias carótidas previstas por modelo hemodinâmico

Tortuosity and bifurcations in carotid arteries alter the blood flow, causing atherosclerosis. Objectives:The aim of the present study is to analyze the effect of variant vascular anatomy in the cervical region on development of atherosclerosis by microanatomical examination. Methods: The effect of blood flow at anomalous bends and bifurcations was observed in right carotid arteries of a seventy year old female cadaver. Fifteen histological slides were prepared from the carotid arteries and interpreted to verify predictions of atherosclerosis. Results: The model predicts atherosclerosis at bends, bifurcations and large aperture arteries. Microanatomical examination revealed presence of atherosclerosis of varying thickness at the bends and bifurcation in the right carotid arteries, as predicted. Atherosclerosis was also detected in the straight part of the wider common carotid artery. No atherosclerosis was observed in the contralateral carotid arteries. The variant carotid vascular anatomy consisting of bends, bifurcations and wider arteries revealed that the shear stress and velocity of blood flow are reduced at these anomalous sites. Conclusions: Anatomical anomalies such as bends and branching in the carotid arteries alter the irrigation pattern and generate biomechanical forces that cause turbulent flow and reduce shear stress/blood flow velocity. Decreased shear stress and velocity causes development of atherosclerosis. Histological slides established the presence of atherosclerosis at bends and bifurcations and in wider arteries

Tortuosidade e bifurcações das artérias carótidas alteram o fluxo sanguíneo, causando aterosclerose. Objetivos: O objetivo do presente estudo foi analisar o efeito de anatomia vascular variante na região cervical sobre o desenvolvimento de aterosclerose via exame microanatômico. Métodos: O efeito do fluxo sanguíneo em dobras e bifurcações anômalas foi observado nas artérias carótidas do lado direito em um cadáver do sexo feminino de 70 anos de idade. Quinze lâminas histológicas foram preparadas a partir das artérias carótidas e interpretadas para confirmar as previsões de aterosclerose. Resultados: O modelo prevê aterosclerose em dobras, bifurcações e artérias de grande calibre. O exame microanatômico revelou a presença de aterosclerose de densidades variáveis nas dobras e bifurcação das artérias carótidas do lado direito, conforme previsto. Aterosclerose também foi detectada na parte reta da artéria carótida comum mais larga. Não foi observada aterosclerose nas artérias carótidas contralaterais. A anatomia vascular carotídea variante consistindo de dobras, bifurcações e artérias mais largas revelou que a tensão de cisalhamento (shear stress) e a velocidade do fluxo sanguíneo são reduzidos nesses pontos anômalos. Conclusões: Anomalias anatômicas tais como dobras e ramificações das artérias carótidas alteram o padrão de irrigação e geram forças biomecânicas que causam fluxo turbulento e reduzem a tensão de cisalhamento e a velocidade do fluxo. Tensão e velocidade menores causam o desenvolvimento de aterosclerose. As lâminas histológicas estabeleceram a presença de aterosclerose nas dobras e bifurcações nas artérias mais largas

Neutrophil-Lymphocyte ratio in cardiovascular disease risk assessment / Relação Neutrófilo-Linfócito na avaliação de risco de doença cardiovascular

The development of cardiovascular diseases with atherosclerotic origin is associated with a severe inflammatory process. Neutrophils and lymphocytes are cells sensitive to this type of disorder and their ratio, known as the NLR (neutrophil/lymphocyte ratio), has shown to be useful in clinical practice. The aim of this study was to assess the role of NLR in cardiovascular disease risk assessment. We carried out a literature review in the PubMed databases searching for articles published between 2001 to 2017 and found that NLR is in fact a useful marker for cardiovascular disease. Using NLR in patients at cardiovascular risk would be useful to delineate the prognosis of patients with this disease pattern

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.

Óeo de Cártamo (Carthamus tinctorius) aumenta os níveis de colesterol total e LDL-colesterol em modelo experimental de síndrome metabólica / Safflower oil (Carthamus tinctorius L) Intake increases total cholesterol and LDL-cholesterol levels in an experimental model of metabolic syndrome

Fundamentos: O excesso de peso vem sendo considerado um importante problema de saúde pública. Na tentativa de reverter esse quadro, são propostos diversos tipos de tratamento. O óleo de cártamo ( Carthamus tinctorius ) vem sendo utilizado na prevenção/tratamento da obesidade. Objetivos: O objetivo deste trabalho foi avaliar os efeitos terapêuticos desse óleo em um modelo experimental de síndrome metabólica. Métodos: Inicialmente foram utilizados ratos Wistar alimentados com dieta altamente palatável (AP) por dez semanas. Após, os animais receberam a dieta AP com suplementação de óleo de soja (APOS) ou óleo de cártamo (APOC), na dosagem 1,0 ml/1000 g de peso do animal. No final do experimento, a composição corporal, o perfil lipídico e glicemia dos animais foram avaliados. Para a análise estatística, utilizou-se o teste t de Student. Resultados: Na primeira fase (indução da síndrome metabólica), os animais que receberam a dieta AP mostraram ganho de peso (p < 0,001), adiposidade visceral (p = 0,001), glicemia (p = 0,001) e triglicerídeos séricos (p = 0,03) significativamente mais elevados do que aqueles do grupo controle. Além disso, houve uma diferença no peso do fígado (p = 0,01). Esses resultados demonstram que a administração de dieta AP é um modelo eficaz para o estudo experimental da síndrome metabólica. Na segunda etapa, os animais do grupo APOC mostraram aumento de colesterol total (p < 0,05) e de LDL-colesterol (p < 0,001). Conclusão: Sob as condições experimentais referidas, conclui-se que a utilização de óleo de cártamo pode causar efeitos deletérios sobre o perfil lipídico em um modelo experimental de síndrome metabólica

Background: Overweight has been considered an important public health problem. To reverse this situation, various types of treatment are proposed. The safflower oil (Carthamus tinctorius L.) has been used in the prevention/treatment of obesity. Objectives: The aim of this study was to evaluate the therapeutic effects of this oil in an experimental model of metabolic syndrome. Methods: Male Wistar rats initially received a highly palatable (HP) diet for ten weeks for validation of a metabolic syndrome model. Following confirmation, the animals were treated with a HP diet and soybean oil (HPSO) or safflower oil (HPSA) supplementation (1.0 mL/1000 g of animal weight). At the end of the experiment, the body composition, lipid profile and blood glucose levels of the animals were assessed. Student t test was used for statistical analysis. Results: In the first stage (induction of metabolic syndrome), the animals given the HP diet showed gain weight (p < 0.001), visceral adiposity (p = 0.001), and significantly higher levels of blood glucose (p = 0.001) and triglycerides (p = 0.03) than those of the control group. Also, there was a difference in liver weight (p = 0.01). These results demonstrate that the HP diet administration is an effective model for the experimental metabolic syndrome study. In the second stage, the animals of the HPSA group showed increased total cholesterol (p < 0.05) and LDL-cholesterol (p < 0.001) levels. Conclusion: Under the referred experimental conditions, the use of safflower oil can cause possible deleterious effects on the lipid profile in a metabolic syndrome experimental model

Rigidez Arterial: Aspectos Fisiopatológicos e Genéticos / Arterial Stiffness: Pathophysiological and Genetic Aspects

As doenças cardiovasculares (DCV) são a principal causa de morte e representam uma percentagem significativa das internações. No cenário de minimização dos custos ao sistema de saúde, métodos que identifiquem DCV subclínica seriam importantes. Algumas diretrizes incluem a medida da rigidez aórtica e da espessura íntima-média da artéria carótida como métodos para identificação de DCV subclínica em hipertensos. A velocidade de onda de pulso (VOP) é considerada padrão-ouro para avaliar a rigidez arterial. Nesta revisão, abordamos a fisiopatologia e os determinantes da rigidez arterial e justificamos sua inclusão na avaliação do paciente hipertenso dada a associação direta com o risco cardiovascular, como estabelecido na I Diretriz Brasileira de Prevenção Cardiovascular. Apresentamos ainda os principais estudos genéticos deste fenótipo que, dada sua complexidade, pode ser modulado por dezenas de genes. No entanto, um melhor entendimento da relação genética-rigidez arterial, e até mesmo uma intervenção baseada em genótipos, devem ser investigadas em estudos futuros

Endothelial dysfunction in children with type 1 diabetes mellitus

ABSTRACT Objective The purpose of this study was to verify the presence of endothelial dysfunction and initial structural atherosclerotic changes in children with Type 1 diabetes mellitus (T1DM). Subjects and methods The study population comprised 31 diabetic children aged 6 to 12 years, divided into two subgroups according to the duration of the T1DM diagnosis: subgroup 1, with less than 5 years elapsed since diagnosis, and subgroup 2, with more than 5 years elapsed since diagnosis. The control group comprised 58 age-matched healthy children. Ultrasonographic techniques were used to measure the flow-mediated dilatation (FMD) of the brachial artery and the intima-media thickness (IMT) of the carotid arteries. Results Children with T1DM with longer disease duration showed significantly decreased mean values of FMD compared with those in the control group. No significant differences between the groups were found in relation to IMT. The FMD percentage presented a moderate negative correlation with glycated hemoglobin (HbA1c) and fasting glucose levels. Conclusion Our findings suggest that endothelial dysfunction may be already present in children with 5 years or more elapsed since diagnosis, even in the absence of atherosclerotic structural changes. The decreased vasodilation response correlated with hyperglycemia.