Abstract P219: Exercise Training Normalizes Vascular Changes in Aging Hypertension Involving microRNAs Profile and Target Genes

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Tiago Fernandes ◽  
Fernanda R Roque ◽  
Vander J Neves ◽  
João L Penteado ◽  
André C Silveira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Soleus Muscle ◽  
Femoral Artery ◽  
Target Genes ◽  
P Value ◽  
Baseline Heart Rate ◽  
Type I ◽  
Vascular Changes ◽  
Fold Enrichment

MiRNAs profile and target genes involved in hypertension-associated vascular changes were evaluated. In addition, we checked the therapeutic role of exercise training (ET) on these parameters. Spontaneously hypertensive rats (SHR) aged 6 months and their controls Wistar Kyoto (WKY) were divided into 4 groups: SHR, trained SHR (SHR-T), WKY and trained WKY (WKY-T). Swimming ET consisted of 60 min of duration, 1x/day/10 weeks, with 4% caudal body weight workload. SHR showed an increased in systolic blood pressure (207 ± 5.5 mmHg) compared to WKY (133 ± 3.9 mmHg) analyzed by tail-cuff system, with no changes in baseline heart rate. We observed a reduction in VO 2 peak (WKY: 62 ± 1.5; SHR: 53 ± 2.5 mL.kg -1 .min -1 ) accompanied by soleus muscle atrophy (fiber type I - WKY: 4039 ± 195; SHR: 2658 ± 53; type IIa - WKY: 2903 ± 182, SHR: 2050 ± 68; Intermediate - WKY: 2663 ± 136, SHR: 1967 ± 95 μm 2 ) in SHR. Vascular function of femoral artery was similar in SHR and WKY, however, wall-to-lumen ratio was increased in femoral artery (WKY: 0.17±0.01, SHR: 0.27±0.01 a.u.) and muscular arteriole (WKY: 0.54±0.02, SHR: 1.14±0.03 a.u.) accompanied by capillary rarefaction (WKY: 1.2 ± 0.05, SHR: 0.6 ± 0.03 capillary-to-fiber ratio) in soleus muscle from SHR vs. WKY. In contrast, ET promoted reduction in blood pressure and resting bradycardia in trained animals. ET corrected the VO 2 peak reduction, muscle wasting, microvascular remodeling in SHR-T toward control levels. ET downregulated 8 miRNAs (-96, -205, -182, -146b-5p, -140, -328a, -665, -1) and upregulated 3 miRNAs (-499, -208b and -99b) in SHR-T when compared to SHR. Bioinformatics study for functional analysis of the predicted targets genes for the 11 miRNAs restored by ET demonstrated enrichment of different signaling pathways including cell death (p value <0.001; Fold enrichment 16.78) and vascular development (p value < 0.001; Fold enrichment 10.62). Thus, targets involved in angiogenesis and vascular integrity by the VEGF/VEGFR2/AKT/eNOS/Bcl-2 pathway were impaired in hypertension and corrected by ET. The results support the hypothesis that the structural changes arising from the progression of hypertension may be regulated by a set of miRNAs and target genes; and ET participates in restoring the vascular remodeling.

Altered Blood Pressure Reactivity in Adolescent Diabetics

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 616-621
Author(s):  
Kathleen M. Newkumet ◽  
Monica Martin Goble ◽  
Reuben B. Young ◽  
Paul B. Kaplowitz ◽  
Richard M. Schieken
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Vascular Reactivity ◽  
Type I Diabetes ◽  
Glycosylated Hemoglobin ◽  
Isometric Exercise ◽  
Diabetes Duration ◽  
Type I ◽  
Vascular Changes ◽  
And Control

Objective. We examined hemodynamic responses to a variety of physiologic stimuli in 14 normotensive adolescents with type I diabetes and 45 healthy controls to determine whether structural vascular changes contribute to a reduced vasodilator capacity in adolescent diabetics. We asked, in adolescents with type I diabetes: (1) Are structural vascular changes present? (2) Are changes in the systemic vascular bed reflected in abnormal blood pressure regulation? and (3) Is abnormal vascular reactivity associated with either diabetes duration or control? Methodology. Diabetic subjects were outpatients treated at the Medical College of Virginia, ages 13 to 18 years. Diabetes duration averaged 7.5 years. Each subject underwent an echocardiogram, dynamic and isometric exercise testing, and forearm plethysmography. Results. Compared to controls, diabetic subjects had (1) higher systolic and diastolic blood pressure during dynamic and handgrip exercise, (2) decreased forearm vasodilator capacity in response to ischemia, and (3) an increased aortic peak velocity. Group diastolic filling abnormalities were found, but these did not persist after adjustment for heart rate. The following variables were related to both diabetes duration and control (average glycosylated hemoglobin): (1) diastolic blood pressure during dynamic exercise, (2) resting forearm vascular resistance, and (3) forearm vascular reactivity. In addition, diabetes duration correlated with isometric exercise diastolic blood pressure, and diabetes control correlated with resting diastolic blood pressure. Conclusion. In young diabetics we found that (1) abnormalities of the resistance vessels of the forearm may be present, (2) the degree of vascular change is related to diabetes duration and control, and (3) aortic distensibility may be impaired.

scholarly journals Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shunqiao Feng ◽  
Lin Han ◽  
Mei Yue ◽  
Dixiao Zhong ◽  
Jing Cao ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Langerhans Cell Histiocytosis ◽  
Mutation Screening ◽  
Langerhans Cell ◽  
Braf V600e ◽  
P Value ◽  
Type I ◽  
Next Generation ◽  
Mutation Status ◽  
Generation Sequencing

Abstract Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

Effects of testosterone treatment, with and without exercise training, on ambulatory blood pressure in middle‐aged and older men.

2021 ◽  
Author(s):  
Lauren C Chasland ◽  
Daniel J Green ◽  
Markus P Schlaich ◽  
Andrew J Maiorana ◽  
Brian R Cooke ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Ambulatory Blood Pressure ◽  
Older Men ◽  
Middle Aged ◽  
Testosterone Treatment

scholarly journals In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3602
Author(s):  
Elena Genova ◽  
Maura Apollonio ◽  
Giuliana Decorti ◽  
Alessandra Tesser ◽  
Alberto Tommasini ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Supportive Therapy ◽  
P Value ◽  
Type I ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Immune System Activation ◽  
In Vitro Effects

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.

scholarly journals The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
David P. McBey ◽  
Michelle Dotzert ◽  
C. W. J. Melling
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Exercise Training ◽  
Muscle Fibre ◽  
Lipid Content ◽  
Fibre Type ◽  
Insulin Treatment ◽  
Type I

Abstract Background Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT). Purpose: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training. Methods Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis. Results The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT. Conclusions These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

scholarly journals Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women

Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 637
Author(s):  
Shengyan Sun ◽  
Zhaowei Kong ◽  
Qingde Shi ◽  
Haifeng Zhang ◽  
On-Kei Lei ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Fasting Glucose ◽  
Training Group ◽  
Moderate Intensity ◽  
Cardiometabolic Health ◽  
Carbohydrate Restriction ◽  
Obese Women ◽  
Low Carbohydrate Diet

Objective: The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women. Methods: Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m−2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50–60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention. Results: Significant reductions in body weight (− ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (− ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5–6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles. Conclusions: The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.

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