Segurança da Ablação por Cateter de Fibrilação Atrial sob Uso Ininterrupto de Rivaroxabana

Background:Atrial fibrillation (AF) ablation under uninterrupted warfarin use is safe and recommended by experts. However, there is some controversy regarding direct-acting oral anticoagulants for the same purpose.Objective:To evaluate the safety of AF ablation under uninterrupted anticoagulation with rivaroxaban.Methods:A series of 130 patients underwent AF radiofrequency ablation under uninterrupted rivaroxaban use (RIV group) and was compared to a control group of 110 patients under uninterrupted warfarin use (WFR group) and therapeutic International Normalized Ratio (INR). We analyzed death, rates of thromboembolic events, major and minor bleedings, activated clotting time (ACT) levels, and heparin dose in the procedure. The ablation protocol basically consisted of circumferential isolation of the pulmonary veins guided by electroanatomic mapping. It was adopted a statistical significance of 5%.Results:The clinical characteristics of the groups were similar, and the paroxysmal AF was the most frequent type (63% and 59%, RIV and WFR groups). A thromboembolic event occurred in the RIV group. There were 3 patients with major bleeding (RIV = 1 and WFR = 2; p = 0.5); no deaths. Basal INR was higher in the WFR group (2.5 vs. 1.2 ± 0.02; p < 0.0001), with similar basal ACT levels (123.7 ± 3 vs. 118 ± 4; p= 0, 34). A higher dose of venous heparin was used in the RIV group (9,414 ± 199 vs. 6,019 ± 185 IU; p < 0.0001) to maintain similar mean ACT levels during the procedure (350 ± 3 vs. 348.9 ± 4; p = 0.79).Conclusion:In the study population, AF ablation under uninterrupted rivaroxaban showed a safety profile that was equivalent to uninterrupted warfarin use with therapeutic INR.     

Agrupamentos de Fatores de Risco Cardiometabólicos e sua Associação com Aterosclerose e Inflamação Crônica em Adultos e Idosos em Florianópolis,Sul do Brasil

Background The significant increase in cardiovascular diseases in developing countries alerts about their impact on underprivileged populations.Objective To identify the relationship of clusters of metabolic syndrome (MS) components with atherosclerosis and chronic inflammation among adults and elderly.Methods Cross-sectional analysis using data from two population-based cohort studies in Florianópolis, Southern Brazil (EpiFloripa Adult Cohort Study, n = 862, 39.9±11.5 years; EpiFloripa Aging Cohort Study, n = 1197, 69.7±7.1 years). Blood pressure (BP), waist circumference (WC), and lipid and glucose levels were analyzed as individual factors or as clusters (either as the number of components present in an individual or as combinations of components). Outcomes included carotid intima-media thickness (IMT), atherosclerotic plaques, and C-reactive protein (CRP) levels. Multiple linear and logistic regression analyses adjusted for confounding factors were used. The statistical significance adopted was 5%.Results Individuals with high BP, elevated WC, dyslipidemia and hyperglycemia (6.1% of the sample) showed higher IMT and CRP than those negatives for all MetS components. Elevated WC was a common determinant of systemic inflammation, while the coexistence of high BP and elevated WC (clusters of two or three factors) was associated with higher IMT (β between +3.2 and +6.1 x 10-2 mm; p value < 0.05) and CRP (_EXPβ between 2.18 and 2.77; p value < 0.05).Conclusion The coexistence of high BP and elevated WC was associated with increased IMT and CRP levels, but central obesity affected systemic inflammation either alone or in combination with other risk factors.     

VEGF121 como Mediador de Efeitos Cardioprotetores Pós-Hipóxia via CaSR e via da Protease Dependente de Mitocôndria

Background:Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known.Objectives:To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes.Methods:Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant.Results:The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels.Conclusions:Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.     

Dieta Intermitente Atenua a Remodelação Cardíaca Causada pelo Exercício Físico

BackgroundThe effects of non-pharmacological interventions such as calorie restriction and exercise training on health and prevention of cardiovascular diseases have been investigated in clinical and experimental studies.ObjectiveTo analyze the influence of intermittent fasting and exercise training on functional fitness, glycemia and cardiac remodeling.MethodsWistar rats (n=60) were randomly divided into four groups: control, exercise training (ET), intermittent fasting (IF) and exercise training plus intermittent fasting (ETI). Over 12 weeks, control and ET animals were fed daily a standard commercial diet ad libitum , while IF and ETI animals were fed every other day. In addition, the ET and ETI groups were submitted to a running protocol on a treadmill. After this period, functional fitness, nutritional parameters and blood glucose levels were analyzed. In addition to heart morphology, myocardial protein expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was assessed by Western-blot. The results were analyzed using two-way ANOVA and Student-Newman-Keuls test. The level of significance considered was 5%.ResultsExercise training increased functional fitness in the ET and ETI groups and promoted cardiac fibrosis. The combination of intermittent fasting and exercise training resulted in a smaller area under the blood glucose curve and reduced cardiomyocyte cross-sectional area and interstitial collagen fraction in the ETI group compared to ET. ERK and JNK expression levels were similar among groups (p>0.05).ConclusionsIntermittent fasting is associated with improved glucose tolerance and attenuates cardiac remodeling induced by exercise training (Arq Bras Cardiol. 2020; 115(2):184-193)     

Pressão Arterial de Crianças: Associação a Indicadores Antropométricos,Composição Corporal,Aptidão Cardiorrespiratória e Atividade Física

Background:Evidence points to anthropometric and fitness variables as associated factors with children''s blood pressure. Analysing these factors in a single context is a relevant possibility of identifying the weight that each factor can present for the development of arterial hypertension.Objective:Identify the possible associations between anthropometric measurements, body composition, moderate-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF) with blood pressure in children.Methods:Correlational study with a quantitative approach. Sample: 215 schoolchildren aged 6-12 years selected by convenience criteria of a public school in Porto Alegre, Brazil. Blood pressure was measured with a digital sphygmomanometer. For data treatment, the values of systolic and diastolic blood pressure were standardized (Z score) and added. The variables tested as predictors were: MVPA; body fat percentage (BF%); Body Mass Index (BMI); waist-height ratio (WHTR); maturity-offset and CRF. After checking the normality parameters, the crude and adjusted associations (for sex, age and maturity-offset) were tested with linear regression equations. For the analyses, p <0.05 was considered.Results:Three different models indicated the best sets of factors associated with standardized blood pressure. Model 1 (R² = 0.21) consisted of the variables WHTR (β = 9.702) and MVPA (β = −0.021). Model 2 (R² = 0.19) was composed of the variables BMI (β = 0.156) and MVPA (β = −0.021). Model 3 (R² = 0.18) included the variables BF% (β = 0.063) and CRF (β = −0.004).Conclusion:Blood pressure in children is predicted by the body variables BF%, BMI and WHTR, in addition, it is negatively associated with MVPA and CRF.     

Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas

Background Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS).Objective To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS.Methods This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant.Results A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization.Conclusions Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294)     

Estudo Comparativo da Doença Coronariana Microvascular Causada por Doença de Chagas e por Outras Etiologias

BackgroundChagas disease (CD) as neglected secondary form of suspected coronary microvascular dysfunction (CMD).ObjectivesComparison of patients with CMD related to CD (CMD-CE) versus patients with CMD caused by other etiologies (CMD-OE).MethodsOf 1292 stable patients referred for invasive coronary angiography to elucidate the hemodynamic pattern and the cause of angina as a cardinal symptom in their medical history, 247 presented normal epicardial coronary arteries and 101 were included after strict exclusion criteria. Of those, 15 had suspected CMD-CE, and their clinical, hemodynamic, angiographic and scintigraphic characteristics were compared to those of the other 86 patients with suspected CDM-OE. Level of significance for all comparisons was p < 0.05.ResultsPatients with suspected CMD-CE showed most anthropometric, clinical, angiographic hemodynamic and myocardial perfusion abnormalities that were statistically similar to those detected in the remaining 86 patients with suspected CMD-OE. LV diastolic dysfunction, expressed by elevated LV end-diastolic pressure was equally found in both groups. However, as compared to the group of CMD-OE the group with CMD-CE exhibited lower left ventricular ejection fraction (54.8 ± 15.9 vs 61.1 ± 11.9, p= 0.049) and a more severely impaired index of regional wall motion abnormalities (1.77 ± 0.35 vs 1.18 ± 0.26, p= 0.02) respectively for the CMD-OE and CMD-CE groups.ConclusionChronic Chagas cardiomyopathy was a secondary cause of suspected coronary microvascular disease in 15% of 101 stable patients whose cardinal symptom was anginal pain warranting coronary angiography. Although sharing several clinical, hemodynamic, and myocardial perfusion characteristics with patients whose suspected CMD was due to other etiologies, impairment of LV segmental and global systolic function was significantly more severe in the patients with suspected CMD related to Chagas cardiomyopathy. (Arq Bras Cardiol. 2020; 115(6):1094-1101)     

Ablação por Cateter de Taquicardia Atrial Focal com Ativação Precoce Próxima ao Feixe de His,a Partir da Cúspide Aórtica não Coronária

BackgroundAtrial tachycardia (AT) ablation with earliest activation site close to the His-Bundle is a challenge due to the risk of complete AV block by its proximity to His-Purkinje system (HPS). An alternative to minimize this risk is to position the catheter on the non-coronary cusp (NCC), which is anatomically contiguous to the para-Hisian region.ObjectivesThe aim of this study was to perform a literature review and evaluate the electrophysiological characteristics, safety, and success rate of catheter-based radiofrequency (RF) delivery in the NCC for the treatment of para-Hisian AT in a case series.MethodsThis study performed a retrospective evaluation of ten patients (Age: 36±10 y-o) who had been referred for SVT ablation and presented a diagnosis of para-Hisian focal AT confirmed by classical electrophysiological maneuvers. For statistical analysis, a p-value of <0.05 was considered statistically significant.ResultsThe earliest atrial activation at the His position was 28±12ms from the P wave and at the NCC was 3±2ms earlier than His position, without evidence of His potential in all patients. RF was applied on the NCC (4-mm-tip catheter; 30W, 55ºC), and the tachycardia was interrupted in 5±3s with no increase in the PR interval or evidence of junctional rhythm. Electrophysiological tests did not reinduce tachycardia in 9/10 of patients. There were no complications in all procedures. During the 30 ± 12 months follow-up, no patient presented tachycardia recurrence.ConclusionThe percutaneous treatment of para-Hisian AT through the NCC is an effective and safe strategy, which represents an interesting option for the treatment of this complex arrhythmia. (Arq Bras Cardiol. 2021; 116(1):119-126)     

miR-125b acts as anti-fibrotic therapeutic target through regulating Gli3 in vivo and in vitro

Introduction and objectivesLiver fibrosis is a major characteristic of most chronic liver diseases which leads to accumulation of extracellular matrix (ECM) proteins. Hedgehog (Hh) pathway activated by Gli genes participated in the pathogenesis of liver fibrosis. However, the regulatory role of miR-125b in liver fibrosis via targeting Gli genes remains unknown.Materials and methodsRT-qPCR and western blot were employed to the expression levels of mRNA and protein, respectively. The fibrosis level of liver tissue was determined by Masson's trichrome staining. The interaction between miR-125b and Gli3 was tested by luciferase reporter assay. In addition, LX2 cells were activated and CCl₄-induced rat model was used in this study.ResultsmiR-125b was significantly declined in serum samples of the clinical liver fibrosis patient, activated LX2 cells and the liver tissues of the CCl₄-induced rat model. Furthermore, in cellular level, the alpha-smooth muscle actin (α-SMA) and Albumin expressions were ascending and descending in LX2 cells, respectively, with the decline of miR-125b. However, when transfecting with miR-125b mimic, the expressions of α-SMA and Albumin was reversed and Gli3 expression was notably repressed in LX2 cells. The target interaction between miR-125b and Gli3 was determined by dual-luciferase assays. It was further discovered that the changes of α-SMA, Albumin, and Gli3 were similar to the expression trend in LX2 cells with miR-125b mimic transfection.ConclusionThese results suggested that miR-125b might be protective against liver fibrosis via regulating Gli3 and it might be a promising target in the development of novel therapies to treat pathological fibrotic disorders.     

Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats

ABSTRACT

Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown.

Methods: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days. The expression of miR-133a was determined by fluorescence in situ hybridization. The learning and memory were evaluated by step-down, step-through, and morris water maze (MWM) tests.

Results: In streptozotocin-injected rats, hyperglycemia dramatically induced miR-133a ectopic expressions in vascular endothelium, reduced GTPCH1 gene expressions and BH4 levels, which were reversed by berberine administration (1.0 g/kg/day, 8 weeks). Hyperglycemia also inhibited acetylcholine-induced vasorelaxation in middle cerebral artery and reduced blood supply to the brain, which were bypassed by berberine. Ex vivo studies indicated that miR-133a agomirs abolished these beneficial effects of berberine on acetylcholine-induced vasorelaxation, while supplement of L-sepiapterin prevented endothelial dysfunction in middle cerebral artery isolated from rats. By performing step-down, step-through, and MWM tests, we observed that hyperglycemia significantly caused the impairments of learning and memory in streptozotocin-injected rats. Importantly, these aberrant phenotypes in diabetic rats were normalized by berberine therapy. Finally, berberine reduced miR-133a expression, and increased both BH4 levels and NO production in cultured endothelial cells treated with high glucose.

Conclusion: Berberine improves vascular dementia in diabetes, which is possibly related to the suppression of miR-133a ectopic expression in endothelial cells.     

Associação entre Ácido Úrico Sérico e Pré-Hipertensão e Hipertensão entre Adultos Chineses

BackgroundUric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase.ObjectiveTo evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population.MethodsA cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant.ResultsSerum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028–2.872), 1.018 (0.627–1.654) and 1.738 (1.003–3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256–3.298).ConclusionsThis study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.     

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos

BackgroundL-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown.ObjectivesThe present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice.MethodsSixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant.ResultsChemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05).ConclusionThe results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.     

Associação entre Infecção por Heicobacter Pylori e Hipertensão Arterial Sistêmica: Metanálise

Background:Recent epidemiological studies have shown that alterations in microbiota and its metabolites are associated with systemic arterial hypertension. Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens, and the potential association between H. pylori infection and hypertension are controversial.Objective:This study aimed to clarify their association and provide a new theoretical basis for uncovering the pathogenesis of hypertension.Methods:Case-control and cross-sectional studies on the association between H. pylori and hypertension published from 1996 to 2019 indexed in PubMed, Google Scholar, Chinese Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). The pooled odds ratios (OR) and 95% confidence interval (CI) were estimated. I2 was performed to evaluate the statistical heterogeneity. Publication bias was evaluated using Begg’s and Egger’s test. The extracted data was analyzed in Stata 12.0. Statistical significance was defined as p-value < 0.05.Results:A total of 17 studies involving 6,376 cases of hypertension and 10,850 controls were enrolled. H. pylori infection rate in hypertension patients and controls were 64.9% and 56.3%, respectively. A significantly positive association was shown between H. pylori infection and hypertension with an overall OR of 2.07 (95% CI: 1.46–2.94; p < 0.05). Subgroup analysis revealed that the prevalence of H. pylori infection was associated with hypertension in the region of Asia and the case-control group, ORs (95% CI) were 2.26 (1.51-3.38) and 2.53 (1.72-3.72), respectively. After stratifying by detection methods, differences still existed in subgroups (all p < 0.05).Conclusion:This meta-analysis indicated that H. pylori infection is positively associated with hypertension.     

Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina

Background:Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic “dose response” curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling.Objective:To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process.Methods:A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn''s test post hoc analysis. The significance level for all tests was 5%.Results:TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway.Conclusion:VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.     

Os Efeitos da Doxorrubicina na Biossíntese e no Metabolismo do Heme em Cardiomiócitos

Background Doxorubicin is associated with cardiotoxicity and late cardiac morbidity. Heme is related to cellular oxidative stress. However, its specific regulation in cardiomyocytes under doxorubicin effects has not yet been documented.Objective This study seeks to evaluate the changing profiles of rate-limiting enzymes in the heme metabolism pathway under the effect of doxorubicin.Methods H9c2 cardiomyocytes were incubated with doxorubicin at different concentrations (1,2,5,10μM respectively). The real-time PCR and Western Blot were used to determine the mRNA and protein expression for four pivotal enzymes (ALAS1, ALAS2, HOX-1, and HOX-2) regulating cellular heme metabolism, as well as the levels of heme were detected by ELISA. p<0.01 was considered significant.Results This study observed a dose-dependent changing pattern in heme levels in H9c2 cells with the highest level at the 5μM concentration for doxorubicin, which occurred synchronously with the highest upregulation level of ALAS1, as well as the degradative enzymes, HOX-1, and HOX-2 in mRNA and protein expression. By contrast, ALAS2, contrary to the increasing concentrations of doxorubicin, was found to be progressively down-regulated.Conclusion The increase in ALAS1 expression may play a potential role in the heme level elevation when H9c2 cardiomyocyte was exposed to doxorubicin and may be a potential therapeutic target for doxorubicin-induced myocardial toxicity. (Arq Bras Cardiol. 2021; 116(2):315-322)     

Relação entre Resposta Imune Inata do Receptor Toll-Like-4 (TLR-4) e o Processo Fisiopatológico da Cardiomiopatia da Obesidade

BackgroundObesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines.ObjectiveTo test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation.MethodsMale Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student’s t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant.ResultsThe OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB.ConclusionOur findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.     

A Redução do Colágeno Tipo I está Associada ao Aumento da Atividade da Metaloproteinase-2 e da Expressão Proteica de Leptina no Miocárdio de Ratos Obesos

BackgroundObesity is a risk factor for medical complications, including the cardiovascular system. There is limited information on collagen in the heart in obesity. Our previous study showed decreased protein levels of myocardial collagen type I in obese rats fed a high-fat diet for 34 weeks. However, the mechanisms responsible for low levels are not fully elucidated.ObjectiveThe purpose of this study was to test the hypothesis that the reduction in collagen type I is associated with increased metalloproteinase-2 (MMP-2) activity, which is linked to elevated leptin in the myocardium of obese rats.MethodsThirty-day-old male Wistar rats were randomized into two groups, control (standard diet) and obese (high-fat diet), and fed for 34 weeks. The general animal characteristics and metabolic and endocrine profiles were evaluated. Myocardial protein expressions of collagen I, leptin, tissue inhibitors of metalloproteinases (TIMP), and MMP-2 activity were assessed. Pearson correlation was employed to determine the associations between variables. The level of significance was 5%.ResultsThe obese animals had increased adiposity index compared to control. Comorbidities such as glucose intolerance, hyperinsulinemia, insulin resistance, hyperleptinemia, and hypertension were observed in obese rats. Obesity reduced collagen I, TIMP-1, and TIMP-2, and it increased leptin and MMP-2 in the myocardium. There was a negative correlation between collagen I and MMP-2 and a positive correlation between leptin and MMP-2.ConclusionThe hypothesis was confirmed; the reduction in collagen type I is associated with increased MMP-2 activity and leptin expression in the myocardium of obese rats. (Arq Bras Cardiol. 2020; 115(1):61-70)     

Obesidade Visceral e Hipertensão Sistólica como Substratos da Disfunção Endotelial em Adolescentes Obesos

Background:Obesity affects adolescence and may lead to metabolic syndrome (MetS) and endothelial dysfunction, an early marker of cardiovascular risk. Albeit obesity is strongly associated with obstructive sleep apnea (OSA), it is not clear the role of OSA in endothelial function in adolescents with obesity.Objective:To investigate whether obesity during adolescence leads to MetS and/or OSA; and causes endothelial dysfunction. In addition, we studied the possible association of MetS risk factors and apnea hypopnea index (AHI) with endothelial dysfunction.Methods:We studied 20 sedentary obese adolescents (OA; 14.2±1.6 years, 100.9±20.3kg), and 10 normal-weight adolescents (NWA, 15.2±1.2 years, 54.4±5.3kg) paired for sex. We assessed MetS risk factors (International Diabetes Federation criteria), vascular function (Flow-Mediated Dilation, FMD), functional capacity (VO²peak) and the presence of OSA (AHI>1event/h, by polysomnography). We considered statistically significant a P<0.05.Results:OA presented higher waist (WC), body fat, triglycerides, systolic (SBP) and diastolic blood pressure (DBP), LDL-c and lower HDL-c and VO²peak than NWA. MetS was presented in the 35% of OA, whereas OSA was present in 86.6% of OA and 50% of EA. There was no difference between groups in the AHI. The OA had lower FMD than NWA (6.17±2.72 vs. 9.37±2.20%, p=0.005). There was an association between FMD and WC (R=-0.506, p=0.008) and FMD and SBP (R=-0.493, p=0.006).Conclusion:In adolescents, obesity was associates with MetS and caused endothelial dysfunction. Increased WC and SBP could be involved in this alteration. OSA was observed in most adolescents, regardless of obesity. (Arq Bras Cardiol. 2021; 116(4):795-803)     

Effects of metformin on changes of miR-19a and miR-221 expression associated with myocardial infarction in patients with type 2 diabetes

BackgroundThe presence of hyperglycemia is a risk factor for cardiovascular diseases, as it increases the risk of myocardial infarction (MI). Metformin is considered an effective anti-hyperglycemic drug for patients with type 2 diabetes. Prediction of microRNAs is valuable in determining the risk of MI.AimThis study aimed to measure the expression of two microRNAs, which are involved in the risk of MI and vascular stenosis among metformin users and non-users with MI.MethodsIn this study, we analyzed the expression of two microRNAs, collected from the blood samples of 180 subjects with MI, using the quantitative polymerase chain reaction (qPCR) assay. The subjects were categorized into three groups: non-diabetic patients with MI (MIND), diabetic patients with MI not using metformin (MIDMet?), and diabetic patients with MI using metformin (MIDMet+). To assess the sensitivity and specificity of miR-19a and miR-221 expression as potential biomarkers for MI, the receiver operating characteristic curve (ROC) analysis was conducted for both diabetic groups.ResultsThe diabetic MIDMet + group exhibited a significant decrease in the expression levels of miR-221 (7.2 folds) and miR-19a (5.3 folds) as compared to the MIDMet? and MIND groups (p < 0.05). The ROC analysis revealed that the areas under the ROC curve (AUC) for circulating miR-19a and miR-221 were 0.931 and 0.965 in patients with type 2 diabetes, respectively (p < 0.001).ConclusionBased on the present findings, metformin therapy can influence cardiovascular disorders and their outcomes through down-regulation of microRNAs. Also, exploration of microRNAs and the effects of metformin on their reduction can provide a potential therapeutic strategy for patients with type 2 diabetes by reducing the MI risk.