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The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial.

ABSTRACT: Background:Vascular endothelial growth factor (VEGF) and Fibroblast growth factor-2 (FGF2) are angiogenic cytokines in normal tissues and tumors. Evidence suggests that increased growth factor expression in adipose tissue leads to improved vascularity and decreased hypoxia, fibrosis, and inflammation, which may, in turn, reduce post-menopausal breast cancer risk. Objective:We investigated whether or not exercise had dose-response effects on levels of plasma VEGF and FGF2 in postmenopausal women. Methods:Four hundred previously inactive but healthy postmenopausal women aged 50-74?years of age were randomized to 150 or 300?min per week of aerobic exercise in a year-long exercise intervention. VEGF and FGF2 were measured from fasting serum samples with a custom-plex multiplex assay. Results:A high compared to moderate volume of aerobic exercise did not cause chronic changes in plasma VEGF or FGF2 levels in intention-to-treat or per-protocol analyses. Conclusions:We did not detect differences in growth factor levels related to increasing doses of exercise. It is unlikely that changes in VEGF and FGF2 levels mediate the reduction in risk of post-menopausal breast cancer development in associated with increased levels of exercise. Trial registration:Clinicaltrials.gov identifier: NCT01435005.

SUBMITTER: Brenner DR

PROVIDER: S-EPMC6589878 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial.

Brenner Darren R DR Ruan Yibing Y Adams Scott C SC Courneya Kerry S KS Friedenreich Christine M CM

European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity 20190624

<h4>Background</h4>Vascular endothelial growth factor (VEGF) and Fibroblast growth factor-2 (FGF2) are angiogenic cytokines in normal tissues and tumors. Evidence suggests that increased growth factor expression in adipose tissue leads to improved vascularity and decreased hypoxia, fibrosis, and inflammation, which may, in turn, reduce post-menopausal breast cancer risk.<h4>Objective</h4>We investigated whether or not exercise had dose-response effects on levels of plasma VEGF and FGF2 in postme ...[more]

PMID: 31285780

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Project description:Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses' furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.

Project description:Abstract Objectives Obesity imposes risk to cardiometabolic health; however, intentional weight loss in obese older adults remains controversial. Using data from the CROSSROADS Study (clinicaltrials.gov #NCT00955903), this ancillary study investigated effects of exercise with and without intentional weight loss on changes in cardiometabolic risk assessed by four risk-scoring tools. Methods Participants (n = 134, 39% male, 23% African American, 70.2 ± 4.7 y) were randomized to exercise (n = 48), exercise + nutrient-dense weight maintenance diet (n = 44), or exercise + nutrient-dense caloric restriction of 500 kcals/day (n = 42). The following risk scores were calculated using baseline and 12-month data: Framingham risk assessment, Cardiometabolic Disease Staging (CMDS), metabolic syndrome classification by the International Diabetes Federation (IDF), and metabolic syndrome classification by the National Cholesterol Education Program's Adult Treatment Panel (ATP III). Generalized Estimating Equations were employed to determine differences between groups with ethnicity, sex, and age as covariates. Results Group-time interaction was not significant in application of IDF or ATPIII. Group-time interaction was significant for Framingham and CMDS (P = 0.005 and 0.041, respectively). Upon post-hoc analysis, significant within-group improvements in Framingham scores were observed for exercise + weight maintenance (P < 0.001, r = −1.682) and exercise + weight loss (P = 0.020, r = −0.881). In analysis of between-group differences in Framingham scores, a significant decrease was observed in the exercise + weight maintenance group (P = 0.001, r = −1.723) compared to the exercise group. For CMDS, the exercise + weight loss group had significant within-group improvements (P = 0.023, r = - 0.102). For between-group differences in CMDS, the exercise + weight loss group showed significant risk score reduction (P = 0.012, r = −0.142) compared to the exercise group. Conclusions Risk assessment by Framingham and CMDS showed greater sensitivity to change in cardiometabolic risk factors. Results suggest obese older adults can lower cardiometabolic risk by engaging in exercise + weight maintenance or exercise + weight loss by moderate caloric restriction. Funding Sources R01AG033094 NIA, K07AG043588 NIA, P30DK056336 NIDDK.

Project description:BackgroundFew studies have examined recreational physical activity (RPA) after participating in a structured exercise intervention. More specifically, little is known about the long-term effects of exercise interventions in post-menopausal women. This study had two objectives: 1) To compare RPA in postmenopausal women in the exercise group and the control group 12 months after the end of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial; and 2) To apply the Theory of Planned Behaviour (TPB) to identify predictors of RPA 12 months post-intervention among women in the exercise group.MethodsSelf-reported RPA 12-months post-intervention from a validated questionnaire was used to estimate RPA levels for control group (118/160, 74% response) and exercise group participants (126/160, 79% response). Bivariate analysis was used to compare RPA between exercise and control group participants and to identify TPB variables for multivariate analysis. Logistic regression was applied to TPB data collected from self- administered questionnaires at end of trial by exercise group participants (126/160, 79% response) to identify predictors of long-term RPA.ResultsAt 12 months post-intervention, 62% of women in the exercise group were active compared to 58% of controls (p = 0.52). Of the TPB constructs examined, self-efficacy (OR =2.98 (1.08-8.20)) and behavioural beliefs (OR = 1.46 (1.03-2.06)) were identified as predictors of RPA for exercise group participants.ConclusionsLevels of RPA in the exercise and control groups were comparable 12 months post intervention, indicating that participation in the ALPHA trial was associated with increased physical activity in previously inactive women, regardless of randomization into either the exercise group or in the control group. Exercise interventions that promote self-efficacy and positive behavioural beliefs have the potential to have long-term impacts on physical activity behaviour, although further research is needed to examine additional psychological, social and environmental predictors of long-term RPA in post-menopausal women.Trial registrationClinicalTrials.gov NCT00522262.

Project description:BackgroundExcess adiposity is characterized by alterations in adipokine secretion such that circulating leptin concentrations are increased with reductions in adiponectin. An emerging biomarker for the assessment of this adipose tissue (AT) dysfunction is the adiponectin:leptin (AL) ratio. A low AL ratio may be suggestive of dysfunctional AT and, consequently, a heightened cardiometabolic disease risk. This ancillary study investigated the relationship between the AL ratio and cardiometabolic health among community-dwelling older adults with obesity, as well as the effects of a 12-month exercise and diet intervention on changes in the AL ratio.MethodsParticipants (n = 163, 70.2 ± 4.7 years, 38.0% male) were randomized to the exercise only group, exercise + nutrient-dense weight maintenance group (exercise + weight maintenance), or exercise + nutrient-dense caloric restriction of 500 kcal/d group (exercise + intentional weight loss) (clinicaltrials.gov #NCT00955903). Total and regional adiposity as determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months.ResultsThe AL ratio was significantly (p < 0.05) inversely correlated with body mass index, waist circumference, measures of adiposity, and insulin among all participants at baseline. Among females only, significant positive and inverse correlations were also observed between this ratio and high-density lipoprotein cholesterol and the inflammatory biomarkers high sensitivity C-reactive protein and interleukin-6, respectively. While controlling for biological sex, a significant time by intervention group interaction effect (p < 0.05) was observed such that the AL ratio significantly increased from baseline to study completion among participants in the exercise + weight maintenance group and exercise + intentional weight loss group. Post hoc analysis revealed that the exercise + intentional weight loss group exhibited a significantly greater AL ratio at study completion compared to other groups (p < 0.05 all).ConclusionsResults are in support of the AL ratio as a measure of AT dysfunction among older adults. Furthermore, results suggest that a 12-month exercise and diet intervention with intentional weight loss assists in improving the AL ratio in this population.

Project description:BACKGROUND AND AIMS:The objective of this study was to assess the feasibility (ability to recruit participants and develop the 12-month intervention), acceptability (retention of participants in the intervention), and impact on systemic inflammation and Dietary Inflammatory Index (DII®) scores over a 12-month DII-based intervention. METHODS:Adults were recruited to participate in a self-selection trial (intervention: n = 61, in-person classes; control: n = 34, newsletters). Classes included participatory cooking and dietary recommendations focused on consuming a plant-based diet rich in anti-inflammatory foods (spices, vegetables, etc.). Changes in markers of inflammation, lipids, and DII were analyzed using general linear models with repeated measurements. RESULTS:At 3 months, intervention participants had significantly lower DII scores (-2.66 ± 2.44) compared to controls (-0.38 ± 2.56) (p < 0.01); but not at 12 months (P = 0.10). The only biomarker to approach a significant group effect or group-by-time interaction was CRP (P = 0.11 for the group-by-time interaction). CRP decreased by -0.65 mg/L (95%CI = 0.10-1.20, P = 0.02) at 12 months in the intervention group; no significant decrease was seen for the control group. With both groups combined at 3 months, those with the greatest decrease/improvement in DII score (tertile 1) compared with those whose scores increased (tertile 3) had greater reductions in CRP (-1.09 vs. +0.52 mg/L, P = 0.04), total cholesterol (-9.38 vs. +12.02 mg/dL, P = 0.01), and LDL cholesterol (-11.99 vs. +7.16 mg/dL, P = 0.01). CONCLUSIONS:Although the intervention group had reductions in DII and CRP, main inflammation and lipid outcomes did not differ between groups. Overall, those participants with the largest reduction in DII scores had the largest reductions in CRP and LDL and total cholesterol. Future interventions may need to have more components in place to support maintenance and continued reductions in the DII. CLINICALTRIALS. GOV IDENTIFIER:NCT02382458.

Project description:Abstract Objectives The Visceral Adiposity Index (VAI) was developed to estimate adipose tissue dysfunction as well as visceral fat distribution. In an ancillary analysis of the CROSSROADS Study (clinicaltrials.gov #NCT00955903), this study investigated the effects of exercise with and without intentional energy restriction on VAI changes among older adults with obesity. Methods Participants (n = 163, 37.4% male, 70.3 ± 4.7 years) were randomized to the following groups: exercise only, exercise + nutrient-dense weight maintenance diet, and exercise + nutrient-dense energy restriction of 500 kcal/d. Visceral adiposity determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months. Waist circumference, body mass index, triglycerides, and high-density lipoprotein (HDL) cholesterol were used to compute VAI at both time points. Data were analyzed utilizing Spearman's correlations and general linear models to determine differences among groups following adjustment for covariates. Results Among all participants, significant correlations were observed between VAI and glucose, insulin, tumor necrosis factor-alpha (TNF-α), and the adiponectin: leptin ratio at baseline (r = 0.343, P < 0.001; r = 0.363, P < 0.001; r = 0.200, P = 0.011; r = −0.246, P = 0.002, respectively). DXA and MRI measures of visceral adiposity were not significantly correlated with VAI. Upon completion of the 12-month study period, there were significant differences in VAI among groups [F (2,137) = 5.957, P = 0.003)]. Post hoc analysis revealed that VAI was significantly lower in the exercise + nutrient-dense energy restriction group compared to the exercise only group (P = 0.002). Conclusions Results suggest that VAI may be an adequate measure of adipose tissue dysfunction, yet its ability to estimate levels of visceral adiposity warrants further investigation to determine clinical utility. Nonetheless, results suggest that an exercise + nutrient-dense energy restriction intervention may reduce VAI among older adults with obesity. Funding Sources NIH.

Dataset Information

The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial.

Publications

The impact of exercise on growth factors (VEGF and FGF2): results from a 12-month randomized intervention trial.

Similar Datasets

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