Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis.

Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.

Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats.

OBJECTIVE: Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. METHODS: Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. RESULTS: Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7 ±â€Š9.86 vs. OS: -75.7 ±â€Š19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4 ±â€Š0.4 and -2.6 ±â€Š0.4 vs. OS: -0.6 ±â€Š0.3 and -1.3 ±â€Š0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. CONCLUSION: Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.

Impact of exercise training associated with enalapril treatment on blood pressure variability and renal dysfunctions in an experimental model of arterial hypertension and postmenopause.

OBJECTIVE: In this study, we aimed to investigate the effects of the concurrent exercise training (CET) associated with the enalapril maleate on blood pressure variability (BPV) and renal profile in an experimental model of arterial hypertension (AH) and postmenopause. METHODS: Female ovariectomized spontaneously hypertensive rats (SHR) were distributed into 4 groups (n = 8/group): sedentary (SO), sedentary + enalapril (SOE), trained (TO) and trained + enalapril (TOE). Both enalapril (3mg/kg) and CET (3 days/week) were conducted during 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation and oxidative stress were assessed. RESULTS: The SOE, TO e TOE groups presented decreased systolic BP compared with SO. Both trained groups (TO and TOE) presented lower BPV and increased baroreflex sensitivity (TO: 0.76 ± 0.20 and TOE: 1.02 ± 0.40 vs. SO: 0.40 ± 0.07 ms/mmHg) compared with SO group, with additional improvements in TOE group. Creatinine and IL-6 levels were reduced in SOE, TO and TOE compared with SO group, while IL-10 was increased only in TOE group (vs. SO). Enalapril combined with CET promote reduction in lipoperoxidation (TOE: 1.37 ± 0.26 vs. SO: 2.08 ± 0.48 and SOE: 1.84 ± 0.35 µmol/mg protein) and hydrogen peroxide (TOE: 1.89 ± 0.40 vs. SO: 3.70 ± 0.19 and SOE: 2.73 ± 0.70 µM), as well as increase in catalase activity (vs. sedentary groups). The tubulointerstitial injury was lower in interventions groups (SOE, TO and TOE vs. SO), with potentialized benefits in the trained groups. CONCLUSIONS: Enalapril combined with CET attenuated BPV and baroreflex dysfunctions, probably impacting on end-organ damage, as demonstrated by attenuation in the AH-induced renal inflammations, oxidative stress and morphofunctional impairments in postmenopausal rats.

Impact of an active lifestyle on cardiovascular autonomic modulation and oxidative stress in males with overweight and parental history of hypertension.

Family history of hypertension is associated with early autonomic dysfunction and increased oxidative stress. These alterations have been found to be reinforced by the overweight factor. Conversely, an active lifestyle is effective in improving the mechanisms regulating blood pressure control. Hence, we ought to investigate the effects of an active lifestyle on the hemodynamic, autonomic and oxidative stress parameters in individuals carrying both family history of hypertension and overweight risk factors. Fifty-six normotensive males were divided into four groups: eutrophic offspring of normotensive parents (EN, n = 12), eutrophic and inactive with hypertensive parents (EH, n = 14), overweight and inactive with hypertensive parents (OH, n = 13), and overweight and physically active with hypertensive parents (OAH, n = 17). Cardiovascular autonomic modulation was assessed by heart rate (HRV) and blood pressure (BPV) variability indexes. Oxidative stress included pro/antioxidant markers and nitrite concentration. Inactive offspring of hypertensive parents (EH and OH) showed higher LFSBP (vs EN), an indicator of sympathetic outflow to the vasculature and reduced anti-oxidant activity (vs EN), while higher pro-oxidant markers were found exclusively in OH (vs EN and EH). Conversely, the OAH group showed bradycardia, higher vagally-mediated HFabs index (vs OH and EN), lower sympathovagal balance (vs OH) and preserved LFSBP. Yet, the OAH showed preserved pro/antioxidant markers and nitrite levels. Our findings indicates that overweight offspring of hypertensive parents with an active lifestyle have improved hemodynamic, cardiac autonomic modulation and oxidative stress parameters compared to their inactive peers.

Parental fructose consumption induces early baroreflex dysfunction in offspring: impact on arterial pressure and on insulin resistance.

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Concurrent exercise training induces additional benefits to hydrochlorothiazide: Evidence for an improvement of autonomic control and oxidative stress in a model of hypertension and postmenopause.

OBJECTIVE: This study aimed to evaluate whether exercise training could contribute to a better modulation of the neurohumoral mechanisms linked to the pathophysiology of arterial hypertension (AH) in postmenopausal hypertensive rats treated with hydrochlorothiazide (HCTZ). METHODS: Female spontaneously hypertensive rats (SHR) (150-200g, 90 days old) were distributed into 5 hypertensive groups (n = 7-8 rats/group): control (C), ovariectomized (O), ovariectomized treated with HCTZ (OH), ovariectomized submitted to exercise training (OT) and ovariectomized submitted to exercise training and treated with HCTZ (OTH). Ovarian hormone deprivation was performed through bilateral ovariectomy. HCTZ (30mg/kg/day) and concurrent exercise training (3d/wk) were conducted lasted 8 weeks. Arterial pressure (AP) was directly recorded. Cardiac effort was evaluated using the rate-pressure product (RPP = systolic AP x heart rate). Vasopressin V1 receptor antagonist, losartan and hexamethonium were sequentially injected to evaluate the vasopressor systems. Inflammation and oxidative stress were evaluated in cardiac tissue. RESULTS: In addition to the reduction in AP, trained groups improved RPP, AP variability, bradycardic (OT: -1.3 ± 0.4 and OTH: -1.6 ± 0.3 vs. O: -0.6 ± 0.3 bpm/mmHg) and tachycardic responses of baroreflex sensitivity (OT: -2.4 ± 0.8 and OTH: -2.4 ± 0.8 vs. O: -1.3 ± 0.5 bpm/mmHg), NADPH oxidase and IL-10/TNF-α ratio. Hexamethonium injection revealed reduced sympathetic contribution on basal AP in OTH group (OTH: -49.8 ± 12.4 vs. O: -74.6 ± 18.1 mmHg). Furthermore, cardiac sympathovagal balance (LF/HF ratio), IL-10 and antioxidant enzymes were enhanced in OTH group. AP variability and baroreflex sensitivity were correlated with systolic AP, RPP, LF/HF ratio and inflammatory and oxidative stress parameters. CONCLUSION: The combination of HCTZ plus concurrent exercise training induced additional positive adaptations in cardiovascular autonomic control, inflammation and redox balance in ovariectomized SHR. Therefore, combining exercise and medication may represent a promising strategy for managing classic and remaining cardiovascular risks in AH.

Combined Exercise Training Promotes More Benefits on Cardiovascular Autonomic Modulation in Ovariectomized Rats Than Isolated Aerobic or Resistance Training.

Introduction: Cardiovascular risk increase after ovarian deprivation has been extensively demonstrated by our research group through cardiovascular autonomic analysis. Interventions involving different types of exercises, such as resistance exercises or combined exercises (aerobic and resistance) have been widely recommended to prevent or minimize neuromuscular decline in postmenopausal women, which is aggravated by a sedentary lifestyle. Experimentally, the cardiovascular effects of resistance or combined training, as well as comparison between aerobic, resistance, and combined training, in ovariectomized animals are scarce. Purpose: In this study, we hypothesized that the combination of aerobic and resistance training may be more effective in preventing muscle mass loss, as well as improving cardiovascular autonomic modulation and baroreflex sensitivity, than aerobic or resistance training individually in ovariectomized rats. Animals and Methods: Female rats were divided into 5 groups: sedentary (C); ovariectomized (Ovx); trained ovariectomized submitted to aerobic training (OvxAT); resistance training (OvxRT); combined training (OvxCT). Exercise training lasted 8 weeks, with the combined group alternating between aerobic training and resistance training every other day. At the end of the study, glycemia and insulin tolerance were evaluated. Arterial pressure (AP) was directly recorded. Baroreflex sensitivity was assessed by heart rate response to changes in arterial pressure. Cardiovascular autonomic modulation was evaluated by spectral analysis. Results: Combined training was the only training regime that increased baroreflex sensitivity for tachycardic response and reduced all systolic blood pressure variability parameters. Furthermore, all animals submitted to exercise training on a treadmill (OvxAT and OvxCT) presented lower systolic, diastolic, and mean pressure, as well as improvements in the autonomic modulation for the heart. Conclusion: Combined training showed to be more effective than isolated aerobic and resistance training, mixing the isolated benefits of each modality. It was the only modality able to increase baroreflex sensitivity to tachycardic responses, reduce arterial pressure and all parameters of vascular sympathetic modulation.

Computerized working memory training for hypertensive individuals with executive function impairment: a randomized clinical trial.

Background: Hypertension is associated with working memory (WM) impairment. However, the benefits of Cogmed WM training for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed's effects on the WM performance of hypertensive individuals with executive function (EF) impairment. Methods: We included 40 hypertensive patients (aged 40-70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive 10 weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were verbal memory, visuospatial ability, executive function, global cognition, and the neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Results: Cogmed did not show a significant effect on WM or any other cognitive outcome post-training. However, under the WM-low load and WM-high load conditions of the fMRI, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analyses) and left inferior frontal lobe (PP analysis) in comparison to the control group. Conclusion: The Cogmed showed no effects on the WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting a more efficient neuronal activity after training.

Effect of aerobic and resistance exercise training on endothelial function in individuals with overweight and obesity: a systematic review with meta-analysis of randomized clinical trials.

The objective of this systematic review was to examine the effects of exercise training on endothelial function in individuals with overweight and obesity. Our review study included only randomized controlled trials (RCTs) involving adults (≥ 18 years of age) with body mass index (BMI) ≥ 25.0 kg/m2. Our search was conducted in the electronic bases MEDLINE (PubMed), Cochrane, LILACS and EMBASE and in the gray literature. We performed random-effects analyses for effect estimates and used 95% prediction intervals (95% PI) for estimating the uncertainty of the study results. There were selected 10 RCTs involving 14 groups (n = 400). The quality assessment of studies using Cochrane risk-of-bias 2 (RoB 2) tool identified some concerns. Exercise training resulted in improved flow-mediated dilation (FMD) in individuals with overweight and obesity (p < 0.001) compared to the no-exercise control group. This effect of training modalities on FMD was seen for aerobic training (p < 0.001) but not for resistance training (p = 0.051). There was no difference in FMD in response to exercise training by BMI classification (overweight, obesity, overweight + obesity), p = 0.793. The present results are consistent with the notion that aerobic exercise training elicits favorable adaptations in endothelial function in individuals with overweight and obesity. Our findings should be interpreted with caution because of the small number of studies included in this review.

Enteral administration of the protease inhibitor gabexate mesilate preserves vascular function in experimental trauma/hemorrhagic shock.

Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration-response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10-10 to 10-5 M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration-response curve to the α1 adrenergic agonist phenylephrine compared to arteries from Shock-control animals (- logEC50: - 5.73 ± 0.25 vs. - 6.48 ± 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (- logEC50: - 6.62 ± 0.21 vs. - 7.13 ± 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 ± 9 vs. 17.63 ± 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r2 = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 ± 7.91 vs. 64.95 ± 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.

Effects of Exercise Intensity on Cardiometabolic Parameters of Ovariectomized Obese Mice.

The aim of this study was to compare the effects of continuous-moderate vs. high-intensity interval aerobic training on cardiovascular and metabolic parameters in ovariectomized high-fat-fed mice. C57BL/6 female ovariectomized were divided into four groups (n=8): low-fat-fed sedentary (SLF); high-fat-fed sedentary (SHF); high-fat-fed moderate-intensity continuous trained (MICT-HF); and high-fat-fed high-intensity interval aerobic trained (HIIT-HF). The high-fat diet lasted 10 weeks. Ovariectomy was performed in the fourth week. The exercise training was carried out in the last four weeks of protocol. Fasting glycemia, oral glucose tolerance, arterial pressure, baroreflex sensitivity, and cardiovascular autonomic modulation were evaluated. Moderate-intensity continuous training prevented the increase in arterial pressure and promoted a reduction in HR at rest, associated with an improvement in the sympathovagal balance in MICT-HF vs. SHF. The high-intensity interval training reduced blood glucose and glucose intolerance in HIIT-HF vs. SHF and MICT-HF. In addition, it improved sympathovagal balance in HIIT-HF vs. SHF. Moderate-intensity continuous training was more effective in promoting cardiovascular benefits, while high-intensity interval training was more effective in promoting metabolic benefits.

Brief periods of transcutaneous auricular vagus nerve stimulation improve autonomic balance and alter circulating monocytes and endothelial cells in patients with metabolic syndrome: a pilot study.

BACKGROUND: There is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS. METHODS: We conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up. RESULTS: An improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile. CONCLUSION: These results are of interest for further study of TAVNS as treatment of MetS.

Food readjustment plus exercise training improves cardiovascular autonomic control and baroreflex sensitivity in high-fat diet-fed ovariectomized mice.

Despite consensus on the benefits of food readjustment and/or moderate-intensity continuous exercise in the treatment of cardiometabolic risk factors, there is little evidence of the association between these two cardiovascular risk management strategies after menopause. Thus, the objective of this study was to evaluate the effects of food readjustment and/or exercise training on metabolic, hemodynamic, autonomic, and inflammatory parameters in a model of loss of ovarian function with diet-induced obesity. Forty C57BL/6J ovariectomized mice were divided into the following groups: high-fat diet-fed - 60% lipids throughout the protocol (HF), food readjustment - 60% lipids for 5 weeks, readjusted to 10% for the next 5 weeks (FR), high-fat diet-fed undergoing moderate-intensity exercise training (HFT), and food readjustment associated with moderate-intensity exercise training (FRT). Blood glucose evaluations and oral glucose tolerance tests were performed. Blood pressure was assessed by direct intra-arterial measurement. Baroreflex sensitivity was tested using heart rate phenylephrine and sodium nitroprusside induced blood pressure changes. Cardiovascular autonomic modulation was evaluated in time and frequency domains. Inflammatory profile was evaluated by IL-6, IL-10 cytokines, and TNF-alpha measurements. Only the exercise training associated with food readjustment strategy induced improved functional capacity, body composition, metabolic parameters, inflammatory profile, and resting bradycardia, while positively changing cardiovascular autonomic modulation and increasing baroreflex sensitivity. Our findings demonstrate that the association of these strategies seems to be effective in the management of cardiometabolic risk in a model of loss of ovarian function with diet-induced obesity.

Associação do estado nutricional com pressão arterial de escolares do município de Porto Alegre / Association of nutritional status with blood pressure of school children in the municipality of Porto Alegre

Introdução: De acordo com a Organização Mundial da Saúde, as Doenças Cardiovasculares têm sido a principal causa de morte nas últimas duas décadas. Como fatores de risco para estas doenças podemos citar o excesso de peso e níveis alterados de pressão arterial. Mudanças nesse panorama requerem, principalmente, um foco na prevenção dessas doenças. Identificar o aumento dos níveis pressóricos precocemente e avaliar o estado nutricional da população mais jovem é de extrema importância para a prevenção de doenças crônicas, especialmente as cardiovasculares. Objetivo: Avaliar a associação entre estado nutricional e pressão arterial em escolares do município de Porto Alegre/RS. Metodologia: Trata-se de um estudo transversal, realizado com crianças e adolescentes, de ambos os sexos, com idades entre 7 e 17 anos de escolas públicas e privadas no município de Porto Alegre. Resultados: Participaram da pesquisa 1.228 indivíduos. Em relação ao estado nutricional e aos níveis pressóricos, a maioria dos estudantes encontra-se na faixa de normalidade. As variáveis idade, sexo, tipo de escola e classificação do IMC mantiveram-se associadas à prevalência de Hipertensão arterial, mesmo após ajuste para estas variáveis de confusão. Conclusão: No presente trabalho, foi encontrada associação entre o estado nutricional e os níveis de pressão arterial de crianças e adolescentes. Contudo, são necessários mais estudos que explorem as possíveis causas, hereditárias, ambientais e comportamentais para tais achados. (AU)

Introduction: According to the World Health Organization, Cardiovascular Diseases have been the leading cause of death in the last two decades. As risk factors for these diseases, we can mention being overweight and altered levels of blood pressure. Changes in this scenario require, mainly, a focus on the prevention of these diseases. Identifying the increase in blood pressure levels early and assessing the nutritional status of the younger population is extremely important for the prevention of chronic diseases, especially cardiovascular diseases. Objective: To evaluate the association between nutritional status and blood pressure in schoolchildren in the city of Porto Alegre/RS. Methodology: This is a cross-sectional study carried out with children and adolescents, of both sexes, aged between 7 and 17 years old from public and private schools in the city of Porto Alegre. Results: A total of 1,228 individuals participated in the research. Regarding nutritional status and blood pressure levels, most students are in the normal range. The variables age, sex, type of school and BMI classification remained associated with the prevalence of arterial hypertension, even after adjusting for these confounding variables. Conclusion: In the present study, an association was found between nutritional status and blood pressure levels in children and adolescents. However, further studies are needed to explore the possible hereditary, environmental and behavioral causes for such findings. (AU)

Set7 deletion attenuates isoproterenol-induced cardiac fibrosis and delays cardiac dysfunction.

Cardiovascular diseases are the main cause of death worldwide. Recent studies have revealed the influence of histone-modifying enzymes in cardiac remodeling and heart dysfunction. The Set7 methyltransferase regulates the expression of several genes through the methylation of histones and modulates the activity of non-histone proteins. However, the role of Set7 in cardiac remodeling and heart dysfunction remains unknown. To address this question, wild-type (WT) and Set7 knockout (KO) male mice were injected with isoproterenol or saline. WT mice injected with isoproterenol displayed a decrease in Set7 activity in the heart. In addition, WT and Set7 KO mice injected with isoproterenol exhibited cardiac hypertrophy. Interestingly, Set7 deletion exacerbated cardiac hypertrophy in response to isoproterenol but attenuated myocardial fibrosis. Echocardiograms revealed that WT mice injected with isoproterenol had lowered ejection fractions and fractional shortening, and increased E'-wave deceleration time and E/A ratio compared with their controls. Conversely, Set7 KO mice did not show alteration in these parameters in response to isoproterenol. However, prolonged exposure to isoproterenol induced cardiac dysfunction both in WT and Set7 KO mice. Both isoproterenol and Set7 deletion changed the transcriptional profile of the heart. Moreover, Set7 deletion increased the expression of Pgc1α and mitochondrial DNA content in the heart, and reduced the expression of cellular senescence and inflammation markers in response to isoproterenol. Taken together, our data suggest that Set7 deletion attenuates isoproterenol-induced myocardial fibrosis and delays heart dysfunction, suggesting that Set7 plays an important role in cardiac remodeling and dysfunction in response to stress.

Ventilatory Muscle Training for Early Cardiac Rehabilitation Improved Functional Capacity and Modulated Vascular Function of Individuals Undergoing Coronary Artery Bypass Grafting: Pilot Randomized Clinical Trial.

Background: Cardiac rehabilitation with aerobic exercises is the first strategy for nonpharmacological treatment in the postoperative period of individuals undergoing coronary artery bypass grafting (CABG) to improve functional capacity and vascular health. However, other exercise modalities remain uncertain regarding the same benefits. Objectives: Evaluation of the effect of different modalities of exercise, such as early cardiac rehabilitation on subjects submitted to CABG in the six-minute walk test (6-MWT) and on the percentage of flow-mediated dilatation (FMD) of the brachial artery. Methods: A randomized clinical trial in which 15 patients (62.7 ± 6.7 years) who underwent CABG were randomly assigned to the following groups: isometric (IG, Handgrip Jamar®), ventilatory muscle training (VG, PowerBreathe®) and control (CG, conventional respiratory and motor physiotherapy). All patients were attended to physically twice a day (20 min/session) for a consecutive week after the CABG (hospital admission). Functional capacity was assessed by 6-MWT and endothelial function was assessed through the technique of FMD, before and after (~7 days) admission to CABG. The doppler ultrasound videos were analyzed by Cardiovascular Suite® software (Quipu, Pisa, Italy) to measure %FMD. Statistics: Generalized estimation equation, followed by Bonferroni post hoc (p < 0.05). Results: Systolic, diastolic and mean arterial pressure (SBP/DBP/MAP, respectively) were 133, 76 and 95 mmHg. The groups presented walking meters (m) distance before and after intervention of: IGbasal 357.80 ± 47.15 m vs. IGpost 306.20 ± 61.63 m, p = 0.401 (+51 m); VGbasal 261.50 ± 19.91 m vs. VGpost 300.75 ± 26.29 m, p = 0.052 (+39 m); CG basal 487.83 ± 83.23 m vs. CGpost 318.00 ± 31.08, p = 0.006 (−169 m). %FMD before and after intervention was IGbasal 10.4 ± 4.8% vs. IGpost 2.8 ± 2.5%, p = 0.152; VGbasal 9.8 ± 5.1% vs. VGpost 11.0 ± 6.1%, p = 0.825; CGbasal 9.2 ± 15.8% vs. CGpost 2.7 ± 2.6%, p = 0.710 and resting mean basal blood flow was IGbasal 162.0 ± 55.0 mL/min vs. IGpost 129.9 ± 63.7 mL/min, p = 0.662; VGbasal 83.74 ± 12.4 mL/min vs. VGpost 58.7 ± 17.1 mL/min, p = 0.041; CGbasal 375.6 ± 183.7 mL/min vs. CGpost 192.8 ± 115.0 mL/min, p = 0.459. Conclusions: Ventilatory muscle training for early cardiac rehabilitation improved acute functional capacity and modulated mean flow of individuals undergoing CABG.

Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice.

BACKGROUND/AIMS: An obesogenic diet (high fat and sugar, low fiber) is associated with an increased risk for metabolic and cardiovascular disorders. Previous studies have demonstrated that epigenetic changes can modify gene transcription and protein function, playing a key role in the development of several diseases. The methyltransferase Set7 methylates histone and non-histone proteins, influencing diverse biological and pathological processes. However, the functional role of Set7 in obesity-associated metabolic and cardiovascular complications is unknown. METHODS: Wild type and Set7 knockout female mice were fed a normal diet or an obesogenic diet for 12 weeks. Body weight gain and glucose tolerance were measured. The 3T3-L1 cells were used to determine the role of Set7 in white adipogenic differentiation. Cardiac morphology and function were evaluated by histology and echocardiography. An ex vivo Langendorff perfusion system was used to model cardiac ischemia/reperfusion (I/R). RESULTS: Here, we report that Set7 protein levels were enhanced in the heart and perigonadal adipose tissue (PAT) of female mice fed an obesogenic diet. Significantly, loss of Set7 prevented obesogenic diet-induced glucose intolerance in female mice although it did not affect the obesogenic diet-induced increase in body weight gain and adiposity in these animals, nor did Set7 inhibition change white adipogenic differentiation in vitro. In addition, loss of Set7 prevented the compromised cardiac functional recovery following ischemia and reperfusion (I/R) injury in obesogenic diet-fed female mice; however, deletion of Set7 did not influence obesogenic diet-induced cardiac hypertrophy nor the hemodynamic and echocardiographic parameters. CONCLUSION: These data indicate that Set7 plays a key role in obesogenic diet-induced glucose intolerance and compromised myocardial functional recovery after I/R in obese female mice.

The miRNA-143-3p-Sox6-Myh7 pathway is altered in obesogenic diet-induced cardiac hypertrophy.

NEW FINDINGS: What is the central question of this study? What is the effect of an obesogenic diet on the expression of microRNAs (miRNAs) involved in cardiac hypertrophy in female mice? What is the main finding and its importance? Female mice fed an obesogenic diet exhibited cardiac hypertrophy associated with increased levels of miRNA-143-3p, decreased mRNA levels of Sox6 and increased mRNA levels of Myh7. Inhibition of miRNA-143-3p increased Sox6 mRNA levels and reduced Myh7 expression in cardiomyocytes, and prevented angiotensin II-induced cardiomyocyte hypertrophy. The results indicate that the miRNA-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy. ABSTRACT: Obesity induces cardiometabolic disorders associated with a high risk of mortality. We have previously shown that the microRNA (miRNA) expression profile is changed in obesity-induced cardiac hypertrophy in male mice. Here, we investigated the effect of an obesogenic diet on the expression of miRNAs involved in cardiac hypertrophy in female mice. Female mice fed an obesogenic diet displayed an increased body weight gain, glucose intolerance, insulin resistance and dyslipidaemia. In addition, obese female mice exhibited cardiac hypertrophy associated with increased levels of several miRNAs, including miR-143-3p. Bioinformatic analysis identified Sox6, regulator of Myh7 gene transcription, as a predicted target of miR-143-3p. Female mice fed an obesogenic diet exhibited decreased mRNA levels of Sox6 and increased expression of Myh7 in the heart. Loss-of-function studies in cardiomyocytes revealed that inhibition of miR-143-3p increased Sox6 mRNA levels and reduced Myh7 expression. Collectively, our results indicate that obesity-associated cardiac hypertrophy in female mice is accompanied by alterations in diverse miRNAs, and suggest that the miR-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy.

Higher Perceived Stress as an Independent Predictor for Lower Use of Emotion-Focused Coping Strategies in Hypertensive Individuals.

Introduction: Individuals with high scores of perceived stress (PS) are more likely to develop arterial hypertension (AH) than those with low levels of stress. In addition to this, AH and stress are both independent risk factors for executive function (EF) impairment and worse quality of life (QoL). Therefore, strategies to control and cope with emotional stress are of paramount importance. However, less is known about the association of PS with EF, QoL, and coping in individuals with hypertension. This study aimed to evaluate the association of PS with EF performance, coping strategies use, and QoL in a sample of hypertensive patients. Methods: We assessed a group of 45 hypertensive individuals (mean age = 58.42 ± 8.9 years, 71.11% female). The EF evaluation was: Frontal Assessment Battery; Controlled Oral Word Association Test-FAS; Letter-Number Sequencing subtest from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III); Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test. The type and frequency of coping strategies used were measured by the Brief Coping with Experienced Problems Scale (Brief-COPE). The World Health Organization Quality of Life Questionnaire Bref (WHOQOL-bref) was applied to measure QoL. The associations of the PS with EF performance, coping strategies, and QoL were investigated using univariate and multiple linear regression models adjusted for age, sex, education, systolic pressure, and depression symptoms. Results: In the multivariate analyses, higher PS was an independent predictor for a lower frequency of emotion-focused strategy use (ß = -0.23; p = 0.03). However, PS was not significantly related to EF and Qol in this sample. The lower the PS, the greater the use of emotion-focused coping. Conclusion: Hypertensive individuals with high PS use less frequently positive emotion-focused coping strategies.