Sex differences in the impact of parental obesity on offspring cardiac SIRT3 expression, mitochondrial efficiency and diastolic function early in life

2021 ◽  
Author(s):  
Jussara M. do Carmo ◽  
Ana C. M. Omoto ◽  
Xuemei Dai ◽  
Sydney P. Moak ◽  
Gabriela S. Mega ◽  
...  
Keyword(s):  
Protein Expression ◽  
Diastolic Function ◽  
Maternal Obesity ◽  
Contractile Function ◽  
Systolic Function ◽  
Matrix Metalloproteinase 2 ◽  
Mitochondrial Efficiency ◽  
The Impact ◽  
Sirt3 Expression

Previous studies suggest that parental obesity may adversely impact long-term metabolic health of the offspring. We tested the hypothesis that parental (paternal + maternal) obesity impairs cardiac function in the offspring early in life. Within 1-3 days after weaning, offspring from obese rats fed a high fat diet (HFD-Offs) and age-matched offspring from lean rats (ND-Offs) were submitted to echocardiography and cardiac catheterization for assessment of pressure-volume relationships. Then, hearts were digested and isolated cardiomyocytes were used to determine contractile function, calcium transients, proteins related to calcium signaling, and mitochondrial bioenergetics. Female and male HFD-Offs were heavier (72±2 and 61±4 vs 57±2 and 49 ±1 g), hyperglycemic (112±8 and 115±12 vs 92±10 and 96±8 mg/dL), with higher plasma insulin and leptin concentrations compared to female and male ND-Offs. Compared to male controls, male HFD-Offs exhibited similar systolic function but impaired diastolic function as indicated by increased IVRT (22±1 vs. 17±1), E/E' ratio (29±2 vs. 23±1) and Tau (5.7±0.2 vs. 4.8±0.2). The impaired diastolic function was associated with reduced resting free Ca2+ levels and phospholamban protein expression, increased activated matrix metalloproteinase 2 and reduced SIRT3 protein expression, mitochondrial ATP reserve and ATP-linked respiration. These results indicate that male and female Offs from obese parents have multiple metabolic abnormalities early in life (1-3 days after weaning) and that male, but not female, Offs have impaired diastolic dysfunction as well as reductions in cardiac SIRT3, resting free Ca+2 levels and mitochondrial biogenesis.

scholarly journals The Impact of Maternal Obesity on Human Milk Macronutrient Composition: A Systematic Review and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 934 ◽  
Author(s):  
Gabriela E. Leghi ◽  
Merryn J. Netting ◽  
Philippa F. Middleton ◽  
Mary E. Wlodek ◽  
Donna T. Geddes ◽  
...  
Keyword(s):  
Human Milk ◽  
Maternal Obesity ◽  
Overweight And Obesity ◽  
Cochrane Library ◽  
Maternal Body Mass Index ◽  
Qualitative Synthesis ◽  
Lactating Women ◽  
Maternal Overweight ◽  
The Impact

Maternal obesity has been associated with changes in the macronutrient concentration of human milk (HM), which have the potential to promote weight gain and increase the long-term risk of obesity in the infant. This article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity on the concentrations of macronutrients in HM. EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science, and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction, and quality assessment independently. A total of 31 studies (5078 lactating women) were included in the qualitative synthesis and nine studies (872 lactating women) in the quantitative synthesis. Overall, maternal body mass index (BMI) and adiposity measurements were associated with higher HM fat and lactose concentrations at different stages of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. However, given the considerable variability in the results between studies and low quality of many of the included studies, further research is needed to establish the impact of maternal overweight and obesity on HM composition. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity.

scholarly journals 114 Impact of left ventricular ejection fraction on procedural and long-term outcomes of bifurcation percutaneous coronary intervention

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Guglielmo Gallone ◽  
Francesc Bruno ◽  
Ovidio De Filippo ◽  
Enrico Cerrato ◽  
Saverio Muscoli ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Systolic Function ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Doppler Imaging ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality ◽  
The Impact

Abstract Aims Longitudinal systolic function may integrate information on aortic stenosis (AS) natural history and cardiac comorbidities with potential prognostic implications. We explored the impact of tissue Doppler imaging (TDI)-derived longitudinal systolic function defined by the peak systolic average of lateral and septal mitral annular velocities (average S’) among symptomatic patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). Methods and results 297 unselected patients with severe AS undergoing TAVI from January 2017 to December 2018 at three European centres, with available average S′ at preprocedural echocardiography were retrospectively included. The primary endpoint was the Kaplan Meier estimate of all-cause mortality. After a median 18 months (IQR 12–18) follow-up, 36 (12.1%) patients died. Average S′ was associated with all-cause mortality (per 1 cm/s decrease: HR: 1.29, 95% CI: 1.03–1.60, P = 0.025), with a best cut-off of 6.5 cm/s. Patients with average S′ <6.5 cm/s (55.2% of the study population) presented characteristics of more advanced left ventricular remodelling and functional impairment along with higher burden of cardiac comorbidities, and experienced higher all-cause mortality (17.6% vs. 7.5%, P = 0.007) also when adjusted for in-study outcome predictors (adj-HR: 3.33, 95% CI: 1.25–8.90, P = 0.016). Results were consistent among patients with preserved ejection fraction, normal-flow AS, high-gradient AS and in those without left ventricular hypertrophy. Conclusions Longitudinal systolic function assessed by average S’ is independently associated with long-term all-cause mortality among unselected patients with symptomatic severe AS undergoing TAVI. In this population, an average S′ below 6.5 cm/s best defines clinically meaningful reduced longitudinal systolic function and may aid clinical risk stratification.

scholarly journals The impact of gestational diabetes and maternal obesity on the mother and her offspring

2010 ◽  
Vol 1 (4) ◽  
pp. 208-215 ◽  
Author(s):  
P. M. Catalano
Keyword(s):  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Glucose Intolerance ◽  
Maternal Obesity ◽  
Insulin Response ◽  
Obese Women ◽  
Increased Risk ◽  
Short And Long Term ◽  
The Impact

Thein uteromaternal metabolic environment is important relative to both short and long term development of the offspring. Although poor fetal growth remains a significant factor relative to long-term outcome, fetal overgrowth is assuming greater importance because of the increase in obesity in the world’s populations. Maternal obesity and gestational diabetes are the most common metabolic complications of pregnancy related to fetal overgrowth and more specifically adiposity.Women with gestational diabetes have increased insulin resistance and inadequate insulin response compared with weight-matched controls. Gestational diabetes increases the risk of maternal hypertensive disease (preeclampsia) as well as cesarean delivery. At birth the neonate has increased adiposity and is at risk for birth injury. Multiple studies have reported that children of women with gestational diabetes have a greater prevalence childhood obesity and glucose intolerance; even at glucose concentrations less than currently used to define gestational diabetes, compared with normoglycemic women.Obese women also have increased insulin resistance, insulin response and inflammatory cytokines compared with average weight women both before and during pregnancy. They too are at increased risk for the metabolic syndrome-like disorders during pregnancy that is hypertension, hyperlipidemia, glucose intolerance and coagulation disorders. Analogous to women with gestational diabetes, neonates of obese women are heavier at delivery because of increased fat and not lean body mass. Similarly, these children have an increased risk of childhood adiposity and metabolic dysregulation. Hence, the preconceptional and perinatal period offers a unique opportunity to modify both short and long term risks for both the woman and her offspring.

Abstract 417: Cardiac Akap12 Signalosome Overexpression Exacerbation of Heart Failure and β-arrestin Signaling Pathway

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Hanan Qasim ◽  
Arfaxad Reyes Alcaraz ◽  
Bradley K McConnell
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Groups ◽  
Expression Levels ◽  
Anchoring Protein ◽  
The Impact

Background: Heart failure (HF) is responsible for 1 out of 8 deaths per year in the U.S.A. andis the major cause of death globally. In HF, chronic β-adrenergic receptor (β-AR)stimulation leads to reduced cardiac function due in part to β-AR desensitization.β-arrestins are proteins that play a major role in desensitizing G protein-coupledreceptors (GPCRs) such as β-AR. Previously we reported enhanced cardiacfunction in mice lacking functional A Kinase Anchoring Protein 12 (AKAP12). Inthis study, we aim to investigate the impact of AKAP12 overexpression(oxAKAP12) on HF progression through assessing β-arrestins. Our central hypothesis is that cardiac AKAP12 overexpression potentiates HF developmentby influencing β-arrestin signaling downstream of the β-AR. Methods: HF was developed in WT and oxAKAP12-Tg mice (8-10) weeks old males andfemales, through chronic Isoproterenol (ISO) administration (60mg/kg/day for 14days). Left ventricular homogenates were used for gene expression analysis.Furthermore, AKAP12 was transiently overexpressed in AC16 cells (humancardiomyocytes cell line), to asses protein expression levels and Gαs pathwayactivity, upon treatment with 100 nM of ISO. Results: Cardiac oxAKAP12 in both males and females reduced left ventricular ejectionfraction (EF) by 14.5±2.5% and fractional shortening (FS) by 22.7±2% after 14-days of chronic ISO treatment when compared to control groups. β-arrestin-1gene expression levels were significantly lower (p=0.022) in oxAKAP12 malehomogenates treated with ISO (14 days) compared to control groups.Interestingly, female homogenates overexpressing AKAP12 showed significantlyhigher β-arrestin-1 gene expression levels (p<0.0001) with ISO treatment,compared to control groups. In AC16 cells overexpressing AKAP12 and treatedwith ISO, Gαs activity and β-arrestin-1 protein expression levels were bothreduced by 50% compared to AC16 ISO treated groups. Conclusion: Cardiac oxAKAP12 negatively influences systolic function in both male andfemale mice, potentially through affecting β-arrestin signaling pathway. Thus,designing novel drugs to inhibit AKAP12 is promising to ameliorate HF.

scholarly journals Direct cardiac versus systemic effects of inorganic nitrite on human left ventricular function

2021 ◽  
Author(s):  
Kevin O'Gallagher ◽  
Ana R Cabaco ◽  
Matthew Ryan ◽  
Ali Roomi ◽  
Haotian Gu ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Sodium Nitrite ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Systolic Function ◽  
Left Ventricular ◽  
Lv Function ◽  
Cardiac Contractile Function ◽  
Lv Systolic Function ◽  
Lv Diastolic Function

Background Inorganic nitrite generates nitric oxide (NO) in vivo and is considered a potential therapy in settings where endogenous NO bioactivity is reduced and left ventricular (LV) function impaired. However, the effects of nitrite on human cardiac contractile function, and the extent to which these are direct or indirect, are unclear. Methods and Results We studied 40 patients undergoing diagnostic cardiac catheterisation who had normal LV systolic function and were not found to have obstructive coronary disease. They received either an intracoronary sodium nitrite infusion (8.7-26 mmol/min, n=20) or an intravenous sodium nitrite infusion (50 mg/kg/min, n=20). LV pressure-volume relations were recorded. The primary end point was LV end-diastolic pressure (LVEDP) while secondary end points included indices of LV systolic and diastolic function. Intracoronary nitrite infusion induced a significant reduction in LVEDP, LV end-diastolic pressure-volume relationship (EDPVR) and the time to LV end-systole (LVEST) but had no significant effect on measures of LV systolic function or systemic haemodynamics. Intravenous nitrite infusion induced greater effects, with significant decreases in LVEDP, EDPVR, LVEST, LV dP/dtmin, tau, and mean arterial pressure. Conclusions These results indicate that inorganic nitrite has modest direct effects on human LV diastolic function, independent of LV loading conditions and without affecting LV systolic properties. The systemic administration of nitrite has larger effects on LV diastolic function which are related to reduction in both preload and afterload. These effects of inorganic nitrite indicate a favourable profile for conditions characterized by LV diastolic dysfunction, e.g. heart failure with preserved ejection fraction.

scholarly journals Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise

2017 ◽  
Vol 313 (3) ◽  
pp. H459-H468 ◽  
Author(s):  
Maria Sanz-de la Garza ◽  
Cira Rubies ◽  
Montserrat Batlle ◽  
Bart H. Bijnens ◽  
Lluis Mont ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Diastolic Function ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Systolic Function ◽  
Training Model ◽  
Left Ventricular ◽  
Physiological Adaptation ◽  
Exercise Load

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): −2.9 ± 0.5 vs. −3.3 ± 0.6 s−1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: −3.3 ± 0.6 vs. −3.0 ± 0.4 s−1 and basal SR: −3.3 ± 0.7 vs. −2.7 ± 0.6 s−1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function.

scholarly journals AGE, SEX, AND FRAILTY INFLUENCE AGE-DEPENDENT CHANGES IN VENTRICULAR STRUCTURE AND FUNCTION IN C57BL/6 MICE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S88-S88
Author(s):  
Susan E Howlett ◽  
Alice Kane ◽  
Elise Bisset ◽  
Kaitlyn Keller
Keyword(s):  
Cardiovascular Diseases ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiac Aging ◽  
Lv Mass ◽  
Age Dependent ◽  
The Impact ◽  
Fractional Shortening

Abstract The heart undergoes maladaptive changes during aging that set the stage for cardiovascular diseases, but frail older individuals are most likely to develop such diseases. We investigated the impact of frailty on left ventricular (LV) remodeling in male and female mice (aged 9-23 mos). Ventricular function/structure and frailty were assessed with echocardiography (Vevo 2100) and a frailty index (FI) tool. Fractional shortening (systolic function) increased with age (9 vs 23 mos) in males (27.7±2.6 vs 38.4±1.6%; p&lt;0.05) and females (26.9±1.4 vs 32.5±1.8%; p&lt;0.05); similar results were seen with ejection fraction. Conversely, E/A ratios (diastolic function) declined with age in males (1.9±0.1 vs 1.3±0.1; p&lt;0.05) and females (2.1±0.3 vs 1.6±0.1; p&lt;0.05). LV mass and LV internal diameter (diastole) increased with age in females but not in males, while intraventricular septum (diastole) increased in males only. As age-dependent changes were heterogeneous, we stratified the data by FI scores. Interestingly, fractional shortening (r=0.52; p=0.006) and ejection fraction (r=0.52; p&lt;0.0001) were graded by FI score, but only in males. By contrast, LV mass was graded by frailty, but only in females (r=0.55; p&lt;0.0001). Thus, diastolic function declines with age in both sexes while systolic function actually increases. Aging females display increased LV mass and LV dilation whereas older males exhibit septal thickening. These maladaptive changes are graded by frailty, suggesting that cardiac aging is prominent in those with poor overall health. Age, sex and frailty influence cardiac aging, which may predispose frail older men and women to develop different cardiovascular diseases as they age.

P5499Coronary angioplasty for octogenarian acute coronary syndrome patients? Is it worth it?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Vila Cha Vaz Saleiro ◽  
D Campos ◽  
R Teixeira ◽  
J Lopes ◽  
J P Sousa ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Primary Endpoint ◽  
Systolic Function ◽  
Left Ventricular ◽  
Coronary Syndrome ◽  
Comorbidity Burden ◽  
St Elevation ◽  
Lv Systolic Function ◽  
The Impact

Abstract Background As the population ages, doctors are being challenged by the decision to offer intervention treatment in increasingly older and fragile patients. The comorbidity burden and performance status should be considered when making the decision. Purpose To assess the impact of optimal medical therapy (OMT) versus percutaneous coronary intervention (PCI) in non-ST elevation acute coronary syndrome (ACS) patients older than 80 years. Methods 182 patients older than 80 years old admitted to a single coronary care unit with a diagnosis of non-ST elevation ACS, who survived hospital stay were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created: Group A (OMT group) N=83; Group B (PCI group) N=99. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer curves and Cox regression were conducted to evaluate the impact of OMT versus PCI on the primary endpoint. The mean time of follow-up was 37±29 months. Results Groups were homogenous regarding gender, cardiovascular risk factors, heart failure diagnosis, left ventricular (LV) systolic function and peak troponin I. OMT group patients were older (85.1±3.7 vs 82.7±3.2 years old, P<0.01), had a higher prevalence of chronic kidney disease (CKD) (61.4% vs 46.5%, P<0.05), a lower haemoglobin (Hb) level (12.0±1.9 vs 12.6±1.7 g/dL, P<0.05) and were less likely to receive double antiplatelet therapy at discharge (80.8% vs 100%, P<0.001). 84 patients met the primary outcome. Kaplan-Meyer curves showed increased survival in the PCI group (36.5% vs 59.3%, Log Rank P<0.001 – Figure 1). Nevertheless, PCI was not associated with long-term mortality (HR 1.05, 95% CI 0.98–1.12) in a model adjusted for age, CKD, peak troponin, LV systolic function and Hb level. Only Hb (HR 0.81, 95% CI 0.73–0.93), peak troponin (HR 1.01, 95% CI 1.00–1.01) and LV function (slightly impaired [HR 1.89, 95% CI 1.03–3,48] and moderate/severely impaired [HR 1.96, 95% CI 1.14–3.36]) remained associated with the outcome. Conclusion Increased survival in older patients receiving PCI after a non-ST elevation ACS may be ascribed to the selection of patients with less comorbidities. This reinforces the idea it may be applied in well-fit patients regardless of age. In our elderly population, lower Hb level, peak troponin and impaired LV systolic function appear to be the main contributors to decreased survival, irrespective of intervention.

scholarly journals The cardiac impact of cisplatin-based chemotherapy in survivors of testicular cancer: a 30-year follow-up

2020 ◽  
Author(s):  
Anders W Bjerring ◽  
Sophie D Fosså ◽  
Hege S Haugnes ◽  
Ragnhild Nome ◽  
Thomas M Stokke ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Diastolic Function ◽  
Systolic Function ◽  
Smoking Status ◽  
Blood Pressure Measurement ◽  
The Body ◽  
Lipid Lowering ◽  
Control Group ◽  
Cardiovascular Morbidity And Mortality

Abstract Aims Cisplatin-based chemotherapy (CBCT) is essential in the treatment of metastatic testicular cancer (TC) but has been associated with long-term risk of cardiovascular morbidity and mortality. Furthermore, cisplatin can be detected in the body decades after treatment. We aimed to evaluate the long-term impact of CBCT on cardiac function and morphology in TC survivors 30 years after treatment. Methods and results TC survivors treated with CBCT (1980–94) were recruited from the longitudinal Norwegian Cancer Study in Testicular Cancer Survivors and compared with a control group matched for sex, age, smoking status, and heredity for coronary artery disease. All participants underwent laboratory tests, blood pressure measurement, and 2D and 3D echocardiography including 2D speckle-tracking strain analyses. Ninety-four TC survivors, on average 60 ± 9 years old, received a median cumulative cisplatin dose of 780 mg (IQR 600–800). Compared with controls, TC survivors more frequently used anti-hypertensive (55% vs. 24%, P &lt; 0.001) and lipid-lowering medication (44% vs. 18%, P &lt; 0.001). TC survivors had worse diastolic function parameters with higher E/e′-ratio (9.8 ± 3.2 vs. 7.7 ± 2.5, P &lt; 0.001), longer mitral deceleration time (221 ± 69 vs. 196 ± 57ms, P &lt; 0.01), and higher maximal tricuspid regurgitation velocity (25 ± 7 vs. 21 ± 4 m/s, P = 0.001). The groups did not differ in left or right ventricular systolic function, prevalence of arrhythmias, or valvular heart disease. Cumulative cisplatin dose did not correlate with cardiac parameters. Conclusion No signs of overt or subclinical reduction in systolic function were identified. Long-term cardiovascular adverse effects three decades after CBCT may be limited to metabolic dysfunction and worse diastolic function in TC survivors.

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