GESTATIONAL DIABETES PROGRAMS MITOCHONDRIAL DYSFUNCTION AND IMPAIRS CARDIAC FUNCTION IN THE OFFSPRING

2016 ◽  
Vol 32 (10) ◽  
pp. S82-S83
Author(s):  
S.M. Kereliuk ◽  
K.G. Cheung ◽  
B. Xiang ◽  
L.K. Cole ◽  
T.J. Pereira ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction

Abstract 2769: Impaired Skeletal Muscle Oxygen Utilization Contributes to Exercise Intolerance in Barth Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Carolyn T Spencer ◽  
Randall M Bryant ◽  
Barry Byrne ◽  
Elisabeth Heal ◽  
Renee Margossian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Barth Syndrome ◽  
Exercise Intolerance ◽  
Peak Exercise ◽  
Indirect Measure ◽  
Muscle Oxygen

Objective s: Barth Syndrome (BTHS) is an X-linked mutation in the TAZ gene characterized by cardiolipin deficiency, mitochondrial dysfunction and cardio-skeletal myopathy. We hypothe- sized that abnormal skeletal muscle oxygen (O 2 ) utilization contributes to exercise intolerance in BTHS. Methods : Boys with BTHS (n=13) and healthy male controls (n=7) performed a graded exercise test on a cycle ergometer with continuous metabolic and EKG monitoring. Near infrared spectroscopy (NIRS), an indirect measure of tissue O 2 saturation and index of skeletal muscle O 2 utilization, was applied to the vastus lateralis during exercise. Cardiac function in BTHS was assessed by echocardiography and serum BNP to examine the relationship between resting cardiac function and exercise capacity in BTHS. Results : Age (16±5 vs 13±3 years; p=0.22), BMI (17±3 vs. 20±5; p=0.14) and BSA (1.0±0.5 vs 1.2±0.6 m 2 ; p=0.3) were not different between BTHS and controls. BTHS had lower peak VO 2 (19±6 vs. 52±6 ml/kg/min, p < 0.001), lower % of predicted peak VO 2 (40±10% vs. 115±12%, p=0.0004), lower peak work rate (58±18 vs. 205±69 watts, p=0.0004), and lower peak O 2 pulse (4.6±1.6 vs. 14±6 ml O 2 /kg/beat, p< 0.00001) than controls. Peak HR in BTHS was lower but remained within normal peak predicted rate (172±14 vs. 197±11 bpm, p=0.001). Vastus lateralis tissue O 2 saturation at peak exercise decreased from baseline in controls as expected (-18±16%, p<0.001) but paradoxically increased from baseline in BTHS (+17±14%, p<0.03, p=0.0005 BTHS vs. controls) indicating impaired muscle O 2 utilization. Absolute (r= - 0.70, p<0.0001) and percent (r= - 0.70, p<0.001) change in NIRS from baseline was negatively associated with peak VO 2 . There was no correlation between peak VO 2 and resting EF (55±7%; r=0.12), SF (30±4%; r= -.26), myocardial performance index (0.4±0.1; r= -.3) or serum BNP (232±381; r=0.1). Conclusion : O 2 consumption during exercise in BTHS is severely reduced and caused, at least in part, by impaired skeletal muscle O 2 utilization. Resting cardiac function is not related to O 2 consumption in BTHS but cardiac dysfunction during exercise in BTHS is not excluded without further studies. Mitochondrial dysfunction likely mediates skeletal muscle O 2 utilization deficits during exercise in BTHS.

scholarly journals Cardiac Function in Infants Born to Mothers With Gestational Diabetes　― Estimation of Early Diastolic Intraventricular Pressure Differences ―

2019 ◽  
Vol 1 (9) ◽  
pp. 378-388
Author(s):  
Satoru Iwashima ◽  
Satoshi Hayano ◽  
Yusuke Murakami ◽  
Aki Tanaka ◽  
Yumiko Joko ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Cardiac Function ◽  
Intraventricular Pressure

Evaluation of cardiac function in fetuses of mothers with gestational diabetes

2019 ◽  
Vol 29 (10) ◽  
pp. 1264-1267 ◽  
Author(s):  
Muhammad Mohsin ◽  
Saleem Sadqani ◽  
Kamran Younus ◽  
Zahra Hoodbhoy ◽  
Salima Ashiqali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Cardiac Function ◽  
Gestational Diabetes Mellitus ◽  
Diastolic Function ◽  
Left Atrial ◽  
Myocardial Hypertrophy ◽  
Control Group ◽  
Diabetes Group ◽  
Diabetic Mothers

AbstractObjective:The purpose of this study was to assess fetal cardiac function in normal fetuses (control group) compared to those who are exposed to gestational diabetes mellitus using different echocardiographic measurements, and to explore the application of left atrial shortening fraction in determination of fetal diastolic function with gestational diabetes mellitus.Methods:A total of 50 women with gestational diabetes and 50 women with a healthy pregnancy were included in the study. Fetal echocardiography was performed and structural as well as functional fetal cardiac parameters were measured. Data were compared between with or without fetal myocardial hypertrophy and the control group.Results:In the study group, out of 50 fetuses of gestational diabetic mothers, 18 had myocardial hypertrophy and 32 had normal septal thickness. Gestational age at time of examination did not differ significantly between the control and gestational diabetes group (p = 0.55). Mitral E/A ratio was lower in gestational diabetes group as compared to the control (p < 0.001). Isovolumetric relaxation and contraction times and myocardial performance index were greater in fetuses of gestational diabetic mothers (p < 0.001). In fetuses of gestational diabetic mothers with myocardial hypertrophy, left atrial shortening fraction was lower as compared to those without myocardial hypertrophy and those of the control group (p < 0.001).Conclusions:The results of this study suggest that fetuses of gestational diabetic mothers have altered cardiac function even in the absence of septal hypertrophy, and that left atrial shortening fraction can be used as a reliable alternate parameter in the assessment of fetal diastolic function.

scholarly journals Evaluation of fetal cardiac function in maternal gestational diabetes mellitus by speckle tracking echocardiography

2021 ◽  
Author(s):  
Peina Huang ◽  
Youbin Deng ◽  
Ling Feng ◽  
Yiping Gao ◽  
Xueqing Cheng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Right Ventricle ◽  
Cardiac Function ◽  
Gestational Diabetes Mellitus ◽  
Right Ventricular ◽  
Speckle Tracking ◽  
Speckle Tracking Echocardiography ◽  
Fetal Cardiac Function ◽  
The Right

Abstract The aim of this study was to assess the cardiac function in fetuses of mothers with gestational diabetes mellitus (GDM) by using fetalHQ, a quantitative analysis software for the assessment of fetal cardiac function based on speckle tracking echocardiography. In this prospective cross-sectional study, 49 fetuses exposed to GDM and 50 normal fetuses were enrolled and fetal echocardiography were performed and analyzed. In the GDM group, left ventricular (24 ± 4 vs. 28 ± 4, p < 0.001) and right ventricular global longitudinal strain (23 ± 4 vs. 26 ± 4, p = 0.002) and right ventricular free wall strain (26 ± 6 vs. 29 ± 5, p = 0.006) were significantly lower compared with the control group, whereas there was no significant difference in global spherical index (1.2 ± 0.1 vs. 1.2 ± 0.1, p = 0.425). Additionally, 24-segment transverse fraction shortening of the right ventricle was more impaired than the left and the segments with reduced fraction shortening were mainly located in the mid and apical sections of the right ventricle, and mid section of the left ventricle. In conclusion, fetuses exposed to GDM may have cardiac dysfunction before the onset of cardiac morphologic abnormalities, and the right ventricle is more vulnerable than the left during fetal development.

scholarly journals Cardiac function in fetal and infants born to mothers with gestational diabetes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Iwashima ◽  
Y Yamamoto ◽  
K Takahashi
Keyword(s):  
Gestational Diabetes ◽  
Cardiac Function ◽  
Fasting Blood Glucose ◽  
Pressure Overload ◽  
Secondary Outcome ◽  
Specific Marker ◽  
Myocardial Performance ◽  
Funding Sources ◽  
Study Population ◽  
Serial Change

Abstract Background The intraventricular pressure differences (IVPD) IVPD using color M-mode is a specific marker in infants of mothers with gestational diabetes mellitus (GDM). (Circulation R 2019, 378–388). Purpose This study investigated the myocardial performance of fetuses in mothers with GDM under the new GDM definition. Method The study population comprised of 27 mothers with GDM and the fetus. Women with GDM were defined as those with a glucose metabolism abnormality that existed before or began during the current pregnancy and was diagnosed using OGTTs. The 5 mothers with type 1 or type 2 DM were receiving insulin before their pregnancy. Fetal echo measurements were performed about median gestational age 35 weeks. The primary outcomes were comparisons of the fetal myocardial performance of GDM with insulin administration and without administration using echocardiography with IVPD, and IVPG. The secondary outcome has investigated the relationships between echocardiography parameters, IVPD, and IVPG, and maternal factors. For all statistical analyses, P&lt;0.05 was considered significant. Result In the insulin group was higher RV output (Fig. 2A). Maternal max HbA1c was observed to have a positive correlation with fetal RV output, significantly (Fig. 2B). Maternal max fasting blood glucose was observed to have a negative correlation with the Total, Basal and Mid to apical IVPD, significantly, respectively. Serial change of LV Total IVPD from fetal to after birth shown in Slide. In both groups, LV Total IVPD was increasing from fetal and after birth significantly. Conclusion The mechanism associated with the favorable systolic and diastolic performances in IGDMs is suggested to involve metabolic adaptations in the heart. In diabetic mice, these adaptations seem to prevent the heart from failing during conditions of pressure overload, suggesting a restoration of the balance between glucose and fatty acid utilization is beneficial for cardiac function. In fetal LV and RV-IVPD might be interacted the mother's blood sugar control. These indexes can predict the sensitive fetal and infant's cardiac dysfunction for GDM. FUNDunding Acknowledgement Type of funding sources: None.

Necrostatin-1 reduces cardiac and mitochondrial dysfunction in prediabetic rats

2021 ◽  
Author(s):  
Nattayaporn Apaijai ◽  
Kewarin Jinawong ◽  
Kodchanan Singhanat ◽  
Thidarat Jaiwongkam ◽  
Sasiwan Kerdphoo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Fusion ◽  
Metabolic Parameters ◽  
Vehicle Group ◽  
Mitochondrial Dynamic ◽  
Autonomic Imbalance

High fat diet (HFD) consumption induces prediabetes and left ventricular dysfunction through many pathways including the cell death pathway, necroptosis. Although benefits of necroptosis inhibitor (necrostatin-1 or Nec-1) in the brain of prediabetic rats have been shown, the effects of Nec-1 on cardiac autonomic function, blood pressure, and cardiac function, and the mechanisms involved have not been investigated. Male Wistar rats were fed with either a normal diet (n=8) or HFD (n=24) for 12 weeks to induce prediabetes. Prediabetic rats were randomly assigned into 3 interventional groups (n=8/group): 1) vehicle, 2) Nec-1 (1.65 mg/kg, sc injection), and 3) metformin (300 mg/kg, oral gavage feeding). Treatments lasted for 8 weeks. Normal saline was given to the vehicle group and a non-interventional group. Metabolic parameters, cardiac function and biochemical parameters were assessed. Prediabetic rats exhibited peripheral metabolic impairment as indicated by increased body weight, hyperinsulinemia with euglycemia, and dyslipidemia. Prediabetic rats also exhibited cardiac autonomic imbalance, high blood pressure, cardiac dysfunction, cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and increased necroptosis and apoptosis. Treatment with Nec-1 did not affect peripheral metabolic parameters, however it effectively reduced cardiac autonomic imbalance, blood pressure, and cardiac dysfunction via reduced cardiac inflammation, necroptosis, mitochondrial dysfunction, and increased mitochondrial fusion. Treatment with metformin reduced peripheral metabolic impairment and cardiac dysfunction via decreased cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. In summary, Nec-1 directly suppressed necroptosis, cardiac mitochondrial dysfunction, and increased mitochondrial fusion independent to peripheral metabolic function, leading to an improvement in cardiac function in prediabetic rats.

Abstract 13060: Abrogation of miR-195 Improves Function in Aged Heart by Preventing Telomere Shortening and Mitochondrial Dysfunction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Motoi Okada ◽  
HaWon Kim ◽  
Muhammad Ashraf ◽  
Jun-ichi Kawabe ◽  
Naoyuki Hasebe
Keyword(s):  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Systolic Function ◽  
Critical Role ◽  
Tissue Growth ◽  
Cell Aging ◽  
Mitochondrial Activity ◽  
Fish Analysis ◽  
And Function ◽  
Aging Factors

Background: Recently, we discovered a distinct microRNAs profile in young and old MSCs by microarray which led us to hypothesize that senescence-associated microRNA(miR)-195 plays a critical role in stem cell aging through telomerase reverse transcriptase (tert) deactivation and determined whether direct inhibition of miR-195 in aged myocardium restores juvenile characteristics and improves cardiac function. Methods and Results: To examine the mechanistic participation of miR-195 in cardiac aging and function, we directly injected lentivral miR-195 inhibitor into the normal mice heart through open chest surgery. Interestingly, we observed a significant telomere re-lengthening in myocardium injected with anti-miR-195 as examined by Q-FISH analysis. In addition, heart tissues treated with miR-195 inhibitor markedly restored the expression of anti-aging factors such as Tert, telomeric repeat-binding factor 2 (Trf2) and Sirt1, whereas expression of pro-aging markers including p53 and p16 were reduced. Additionally, we found that mitochondrial activity was significantly improved in miR-195 knocked down heart as examined by cytochrome c oxidase activity assay. To investigate whether abrogation of miR-195 in myocardium improves cardiac function, we performed echocardiography at 4 weeks after injection. The cardiac function was markedly improved in miR-195 knocked down myocardium as evaluated by cardiac performance index, a useful marker for heart failure (0.24±0.05 vs 0.44±0.13, p<0.05, n=6), whereas there was no significant change in systolic function . Furthermore, histological analysis showed that transfection of miR-195 inhibitor markedly reduced fibrosis as well as expression of connective tissue growth factor (CTGF), a fibrogenic master switch, in the aged myocardium as compared to scramble transfected heart. Conclusions: These results demonstrate that abrogation of miR-195 improves cardiac function through restoration of anti-aging factors as well as amelioration of mitochondrial dysfunction. Suppression of miR-195 in aging myocardium is a novel therapeutic strategy for treatment against age-dependent cardiovascular diseases.

Abstract 210: Thioredoxin-2 Inhibits Mitochondrial Ros Generation And Ask1 Activity To Maintain Cardiac Function

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Wang Min ◽  
Qunhua Huang
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Mitochondrial Dysfunction ◽  
Ros Generation ◽  
Contractile Dysfunction ◽  
Ros Production ◽  
Atp Production ◽  
Mitochondrial Ros ◽  
Cellular Apoptosis

Background: Increasing evidence indicates that mitochondrial-derived reactive oxygen species (ROS) and cellular apoptosis contribute to the pathogenesis of cardiac dysfunction. Mitochondrial thioredoxin (Trx2) is a key protein regulating cellular redox and survival, However, but its role in normal cardiac growth has not been determined. Methods and Results: We have generated cardiac-specific Trx2 knockout mice (Trx2-cKO) to determine the physiological importance of the Trx2 system in the heart. Trx2-cKO mice developed a spontaneous dilated cardiomyopathy at 1 month of age with increased heart size, fibrosis, reduced ventricular wall thickness, and progressive contractile dysfunction, resulting in death due to heart failure by 4 months of age. Cardiac changes in Trx2-cKO mice were accompanied by disruption of mitochondrial integrity and function, as evident by alterations in mitochondrial number, ultrastructure, membrane potential and ATP production. Increases in ASK1 signaling and ROS production preceded mitochondrial damage, cellular apoptosis and contractile dysfunction in both Trx2-cKO hearts and isolated cardiomyocytes. Moreover, deletion of ASK1 attenuates ROS production, mitochondrial dysfunction and cellular apoptosis in Trx2-deficient cardiomyocytes. These data indicate that ASK1 is a major target of Trx2 and that activation of ASK1 is causally associated with mitochondrial dysfunction, ROS production and cellular apoptosis. We also detected reduced Trx2 expression and increased ASK1 activity in human hearts from patients with cardiomyopathy, suggesting that this mechanism is clinically important. Conclusion: Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial ROS production and ASK1-dependent apoptosis. These results suggest that pharmacological inhibition of ASK1 may provide a therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure.

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