Angiotensin-(1-7) and Obesity: Role in Cardiorespiratory Fitness and COVID-19 Implications.
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ABSTRACT:
SUBMITTER: Motta-Santos D
PROVIDER: S-EPMC7362166 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Angiotensin-(1-7) and Obesity: Role in Cardiorespiratory Fitness and COVID-19 Implications.
Motta-Santos Daisy D Santos Robson A S RAS Santos Sérgio Henrique Sousa SHS
Obesity (Silver Spring, Md.) 20200901 10
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Project description:The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.
| S-EPMC7531362 | biostudies-literature
Project description:Patients recovering from COVID-19 often report symptoms of exhaustion, fatigue and dyspnoea and present with exercise intolerance persisting for months post-infection. Numerous studies investigated these sequelae and their possible underlying mechanisms using cardiopulmonary exercise testing. We aimed to provide an in-depth discussion as well as an overview of the contribution of selected organ systems to exercise intolerance based on the Wasserman gears. The gears represent the pulmonary system, cardiovascular system, and periphery/musculature and mitochondria. Thirty-two studies that examined adult patients post-COVID-19 via cardiopulmonary exercise testing were included. In 22 of 26 studies reporting cardiorespiratory fitness (herein defined as peak oxygen uptake-VO2peak), VO2peak was < 90% of predicted value in patients. VO2peak was notably below normal even in the long-term. Given the available evidence, the contribution of respiratory function to low VO2peak seems to be only minor except for lung diffusion capacity. The prevalence of low lung diffusion capacity was high in the included studies. The cardiovascular system might contribute to low VO2peak via subnormal cardiac output due to chronotropic incompetence and reduced stroke volume, especially in the first months post-infection. Chronotropic incompetence was similarly present in the moderate- and long-term follow-up. However, contrary findings exist. Peripheral factors such as muscle mass, strength and perfusion, mitochondrial function, or arteriovenous oxygen difference may also contribute to low VO2peak. More data are required, however. The findings of this review do not support deconditioning as the primary mechanism of low VO2peak post-COVID-19. Post-COVID-19 sequelae are multifaceted and require individual diagnosis and treatment.
| S-EPMC9483283 | biostudies-literature
Project description:This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status). Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathways analysis identified gene pathways related to inflammation (e.g., dopaminergic and GABAergic synapse pathways). Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.
2021-08-05 | GSE164873 | GEO
Project description:ObjectiveTo investigate associations of cardiorespiratory fitness (CRF) and different measures of adiposity with cardiovascular disease (CVD) and all-cause mortality in men with known or suspected coronary heart disease (CHD).Patients and methodsWe analyzed data from 9563 men (mean age, 47.4 years) with documented or suspected CHD in the Aerobics Center Longitudinal Study (August 13, 1977, to December 30, 2002) using baseline body mass index (BMI) and CRF (quantified as the duration of a symptom-limited maximal treadmill exercise test). Waist circumference (WC) and percent body fat (BF) were measured using standard procedures.ResultsThere were 733 deaths (348 of CVD) during a mean follow-up of 13.4 years. After adjustment for age, examination year, and multiple baseline risk factors, men with low fitness had a higher risk of all-cause mortality in the BMI categories of normal weight (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.24-2.05), obese class I (HR, 1.38; 95% CI, 1.04-1.82), and obese class II/III (HR, 2.43; 95% CI, 1.55-3.80) but not overweight (HR, 1.09; 95% CI, 0.88-1.36) compared with the normal-weight and high-fitness reference group. We observed a similar pattern for WC and percent BF tertiles and for CVD mortality. Among men with high fitness, there were no significant differences in CVD and all-cause mortality risk across BMI, WC, and percent BF categories.ConclusionIn men with documented or suspected CHD, CRF greatly modifies the relation of adiposity to mortality. Using adiposity to assess mortality risk in patients with CHD may be misleading unless fitness is considered.
| S-EPMC3538467 | biostudies-literature
Project description:IntroductionCardiorespiratory fitness (CRF), as one of the most potent prognostic factors in medicine, is followed longitudinally to guide clinical management. Coronavirus disease 2019 (COVID-19) pandemic-related changes in lifestyle stand to influence CRF.ObjectiveTo assess the influence of the pandemic on perceived CRF in athlete patients and evaluate how perceived CRF change was related to demographics, pre-pandemic measured CRF, and current physical activity (PA).DesignProspective cohort study, utilizing electronic survey.SettingTertiary care sports cardiology clinical practice.ParticipantsAdult athlete patients without COVID-19 with pre-pandemic measured CRF using cardiopulmonary exercise testing.InterventionsNot applicable.Main outcome measuresPerceived change in CRF since pandemic onset; association between perceived CRF change and demographics, PA, health status, and pre-pandemic measured CRF assessed via analysis of variance (ANOVA).ResultsAmong 62 participants (male: 71%, 50.1 ± 12.1 years old), 40% (25/62) reported no change and 32% (20/62) reported an increase in perceived CRF since pandemic onset. Among the 27% (17/62) who reported a decrease in perceived CRF, in most (12/17), this was characterized as only mild. Demographics and pre-pandemic measured CRF did not differ across groups of perceived CRF change. Participants with a moderate or greater decrease in perceived CRF regarded their overall health (via Euro Quality of Life Visual Analogue Scale) as worse than other groups (ANOVA, p = .001). Although total PA was similar across groups, those who had improvement in perceived CRF reported higher levels of moderate intensity PA (ANOVA, p = .008).ConclusionsThe majority of participants perceived that they had maintained or improved CRF over the pandemic. Findings from this study suggest that a reduction in perceived CRF from pre-pandemic values in athletic patients in clinical practice may not result from population-wide pandemic changes in lifestyle. Worse health status and lower levels of moderate intensity PA were associated with perceived reduction in CRF over the pandemic in athlete patients.
| S-EPMC9088663 | biostudies-literature
Project description:BackgroundThe interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans.MethodsSymptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2), obese (BMI 30-35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF.ResultsOver a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50-60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF.ConclusionImproving CRF should be advocated when assessing those at risk for developing AF.
| S-EPMC7596185 | biostudies-literature
Project description:BackgroundEndurance sports primarily attract recreational athletes over 35 years, who impose an exceptionally rigorous and sustained demand on their cardiorespiratory systems.ObjectivesThis study aimed to determine the influence of COVID-19 on the cardiovascular, pulmonary, and skeletal muscle function of endurance athletes with exercise intolerance. Secondly, it aimed to compare the exercise response of endurance athletes post-COVID-19 to those unaffected using cardiopulmonary exercise test-related variables.MethodsThis is a prospective observational cohort study of endurance athletes. An exposure group with protracted exercise tolerance underwent a resting lung function test and maximal cardiopulmonary exercise test. These were repeated after eight weeks of endurance training and compared to the published reference values and a control group of athletes unaffected by COVID-19.ResultsThe post-COVID-19 exposure group (n=57), mean age 44.5±8.1years showed a poorer ventilatory threshold (p=0.004), and workload (p=0.05), with higher respiratory exchange ratio (p=0.05) than the control group (n=34), mean age 41.8±7.7 years. Maximal inspiratory pressure improved at follow-up in the COVID-19 group compared to the controls (p=0.03). Increased odds of pulmonary and skeletal muscle limitation to aerobic capacity were found in the COVID-19 group. The COVID-19 group responded positively to endurance training with improved VO2peak (p=0.005), maximal inspiratory pressure (p=0.04), oxygenpulse (p=0.02), and maximal workload (p<0.001).ConclusionCOVID-19 has led to pulmonary and extrapulmonary limitations to exercise capacity. Tailored intensity and duration of physical activity are vital after COVID-19 to restore skeletal muscle health. This multidisciplinary rehabilitation approach will optimise the resumption of participation in long-distance events.
| S-EPMC11629943 | biostudies-literature
Project description:BackgroundWe aimed to determine if maximal oxygen uptake (V˙O2max), resting heart rate (RHR), and self-reported leisure- time moderate to vigorous physical activity (MVPA) changed over a 3-year follow-up (FU) among industrial workers.MethodsWe assessed cardiorespiratory fitness (CRF) August 2018 and August 2021. The last 17-18 months coincided with the COVID-19 pandemic. Data from 86 participants were collected; demographics by questionnaire and cardiovascular outcomes from medical examination: V˙O2max, RHR, and fat mass (%). Workers reported on their leisure-time MVPA twice. To assess changes in health outcomes we applied a linear mixed model, adjusting for baseline (BL) age, sex, pack-years, shift work, and a 5-month plant shutdown. Further, we adjusted for actual age instead of BL age.ResultsV˙O2max decreased from 39.6 mL/kg/min at BL to 34.0 at FU, a reduction of 5.6 mL/kg/min (95%CI, -7.6, -3.7). Adjusted for actual age, the corresponding figure for V˙O2max was 5.4 mL/kg/min, (95%CI, -7.4, -3.4), an annual loss of 4.6%. RHR increased from 61.3 to 64.4 beats per minute (95%CI, 0.8, 5.4). Self-reported MVPA decreased by 43.9 min/week, (95%CI, -73.5, -14.4).ConclusionsWe observed a decrease in V˙O2max, an increase in RHR and a decrease in self-reported MVPA, suggesting physical inactivity during the COVID-19 pandemic.
| S-EPMC10816953 | biostudies-literature
Project description:BackgroundLow cardiorespiratory fitness (CRF) and obesity are related to the development and maintenance of atrial fibrillation (AF). The aim of this study was to determine the association between CRF, obesity and left atrial (LA) mechanical parameters in patients with AF.MethodsA cohort of 154 consecutive paroxysmal and persistent AF patients (Age: 62 ± 10, 26% female) referred for exercise stress testing and transthoracic echocardiography were included. We included patients in sinus rhythm with preserved left ventricular ejection fraction who were able to complete a maximal exercise test. Left atrial strain in the reservoir (LASr), booster (LASb) and conduit (LASc) phases were assessed using dedicated software. LA stiffness, emptying fraction (LAEF) and LA to LV ratio were calculated using previously described formulas.ResultsCRF was positively associated with LAEF (β = 1.3, 95% CI 0.1-2.3, p = 0.02), reservoir (β = 1.5, 95% CI 0.9-2.1, p < 0.001), booster (β = 0.8, 95% CI 0.4-1.2, p < 0.001) and conduit strain (β = 0.7, 95% CI 0.3-1.1, p = 0.001). We observed an inverse association between CRF and both LA stiffness index (β = -0.02, 95% CI (-0.03)-(-0.01), p < 0.001) and LA to LV ratio (β = -0.03, 95% CI (-0.04)-(-0.01), p < 0.001). Obese patients had significantly higher indexed LA volumes compared to overweight and normal BMI patients. The association between obesity and measures of LA function and stiffness did not reach statistical significance.ConclusionAmong AF patients, higher CRF was independently associated with greater LA function and compliance. Obesity was associated with higher LA volumes yet preserved mechanical function.
| S-EPMC9375161 | biostudies-literature
Project description:This study examined the relation between cardiorespiratory fitness (fitness) and depression symptoms prior to and during COVID-19 among adults seeking preventive medical care. Participants consisted of 967 patients attending the Cooper Clinic (Dallas, TX) pre-pandemic (March 2018-December 2019) and during the pandemic (March-December 2020). The outcome, depression symptoms, was based on the Center for Epidemiological Studies-Depression (CES-D). Maximal metabolic equivalents task (MET) levels for fitness were determined from the final treadmill speed and grade. Multiple linear regression models were computed by sex. Analysis revealed that mean fitness decreased from 11.4 METs (SD = 2.1) prior to the pandemic to 10.9 METs (SD = 2.3) during the pandemic (p-value < 0.001). The mean CES-D score increased from 2.8 (SD = 3.1) before to pandemic to 3.1 (SD = 3.2) during the pandemic (p-value = 0.003). Results from multiple linear regression indicate that increased fitness was associated with a statistically significant decrease in depression scores in men (-0.17 per MET; 95% CI -0.33, -0.02) but not women. This modest decrease may have been tempered by high fitness levels and low depression scores at baseline in this well-educated sample.
| S-EPMC9677558 | biostudies-literature