scholarly journals Adipose-targeted overexpression of mitochondrial-targeted catalase does not improve cardio-metabolic parameters in mice with diet-induced obesity

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A J Croft ◽  
C Kelly ◽  
D Chen ◽  
L Murtha ◽  
S Sugito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Metabolic Dysfunction ◽  
Metabolic Complications ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues ◽  
National Budget ◽  
Diet Induced Obesity ◽  
National Heart Foundation

Abstract Background Obesity is associated with significant cardio-metabolic complications. Adipokines, and cytokines released from adipose tissue (AT) stimulate excessive mitochondrial production of reactive oxygen species (ROS). ROS-mediated oxidative modifications is associated with development of insulin resistance and impaired cardiac function. We hypothesised that adipose-targeted overexpression of mitochondrial-targeted catalase (AT-mCAT) could lead to improvement in diet-induced cardio-metabolic dysfunction. Methods/Results mCAT (floxed) and AdipoQ-Cre mice were crossed to generate mice overexpressing catalase with a mitochondrial-targeting sequence predominantly in AT (AT-mCAT). Wild-type (WT) and AT-mCAT male mice were fed normal chow (NC) or high-fat/high-sucrose (HFHS) diet (36%fat/34%sucrose) for 4 months. At endpoint, echocardiography showed reduced cardiac output in all groups v WT NC (p<0.05); reduced IVSd in AT-mCAT NC and HFHS groups v WT NC (p<0.01); reduced left ventricular ejection fraction in AT-mCAT HFHS v WT NC (p<0.05) and no differences in fractional shortening or E/A ratio between groups. Glucose tolerance tests (2g/kg) showed impairment in WT HFHS and AT-mCAT HFHS v WT NC (p<0.01, p<0.05 respectively). Triglyceride levels were increased in WT HFHS and AT-mCAT HFHS v WT NC (p<0.05). Analysis of hypertrophic signalling in cardiac tissues by ELISA showed p-AKT/total Akt levels were decreased in AT-mCAT hearts regardless of diet (WT NC v AT-mCAT NC p<0.01; WT HFHS v AT-mCAT HFHS p<0.05). Conclusion Our results confirm previous findings that diet-induced obesity is a systemic condition. Targeting adipose tissue with mitochondrial catalase may not be adequate to prevent development of cardio-metabolic dysfunction. More systemic approaches may be required to combat obesity-induced cardio-metabolic impairment. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of Australia

scholarly journals The relationship between glycosylation of proBNP at threonine 71, BNP, BNP1–32 and obesity in patients with heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.K Lewis ◽  
S.D Raudsepp ◽  
T.G Yandle ◽  
C.J Pemberton ◽  
R.N Doughty ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Zealand ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Obese Patients ◽  
Ventricular Ejection Fraction ◽  
National Budget ◽  
National Heart Foundation ◽  
Public Grant

Abstract Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Measurement of BNP and NTproBNP are used in HF for diagnosis and prognosis but levels of these peptides are inappropriately low in obesity, a condition which is associated with increased HF. Cleavage of proBNP to produce BNP and NT-proBNP requires proBNP to be unglycosylated at threonine 71 (T71). Gycosylation at T71 is affected by obesity, resulting in lower plasma NT-proBNP concentrations in patients with higher BMI. However the relationships between BMI, proBNP glycosylation and BNP (particularly the bioactive cardio-protective peptide BNP1-32) have not previously been described. Methods Validated in-house assays for BNP, BNP1-32, proBNP, proBNP unglycosylated at T71 (NG-T71) and the commercial Roche assay for NT-proBNP were applied to plasma samples obtained from patients with HF (n=321, PEOPLE study: Prospective Evaluation of Outcome in Patients with Left Ventricular Ejection Fraction). Results Median (IQR) concentrations of BNP, BNP1-32, proBNP, NG-T71 and NTproBNP were 10.7 (5–21), 5 (2–9), 27.8 (9–62), 6.2 (3–22) and 217 (104–425) pmol/L respectively. BMI was inversely related to NG-T71, NT-proBNP, BNP and BNP1-32 (r=−0.19, −0.40, −0.36 and −0.34 respectively, all p<0.01) but not proBNP (r=0.11, ns). ProBNP levels in patients with BMI above or below 30 kg/m2 were similar (29.8 (11.2–56.6) and 22.5 (3.9–65) pmol/L, p=0.51), whereas NG-T71, NT-proBNP, BNP and BNP1-32 levels were increased (p<0.001) in patients with BMI <30 (11.6 (3–25.6), 263 (153–486), 13.8 (6.5–25.5) and 6.3 (2.8–10.4)) compared to BMI >30 (3 (1–16), 127 (63–274), 7.8 (3–14) and 3.6 (1.1–7) respectively. The BMI >30 group had increased ProBNP:NT-proBNP, ProBNP:BNP and ProBNP:BNP1-32 ratios (all p<0.001) and proBNP:NG-T71 (p=0.037), whereas ratios of NG-T71 to BNP, BNP1-32 or NT-proBNP were not related to BMI. Patients with diabetes (n=90) also had lower BNP, BNP1-32 (both p<0.01), NG-T71 and NT-proBNP concentrations (both p<0.05), but not proBNP (p=0.46), and a trend towards a higher proBNP:BNP1-32 ratio (p=0.06). Discussion and conclusion The negative association between BMI and plasma NT-proBNP and BNP is not well understood. We recently reported that obese patients with HF have reduced circulating levels of proBNP unglycosylated at T71. In this expanded sample we show that whilst proBNP remains unaffected by BMI, both immunoreactive BNP and more specifically bioactive BNP1–32 levels, and NT-proBNP, are decreased with obesity in conjunction with increased glycosylation at T71. Increased glycosylation at proBNP-T71 reduces the amount of proBNP cleaved to form NT-proBNP and BNP resulting in decreased production and lowered circulating concentrations of these clinically used marker peptides. Our results provide a robust mechanism to explain the reduction in NT-proBNP and BNP levels observed in obese patients and confirm this is associated with reduced bioactive BNP1–32. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Foundation of New Zealand, nHealth Research Council of New Zealand

scholarly journals Epicardial Adipose Tissue Role as a Marker of Higher Vulnerability in Patients with Coronary Artery Disease

2018 ◽  
Vol 3 (2) ◽  
pp. 77-83 ◽  
Author(s):  
Tiberiu Nyulas ◽  
Mirabela Morariu ◽  
Nora Rat ◽  
Emese Marton ◽  
Victoria Ancuta Rus ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Left Ventricular Ejection Fraction ◽  
Left Ventricle ◽  
Epicardial Adipose Tissue ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract Background: Epicardial adipose tissue (EAT) has been recently identified as a major player in the development of the atherosclerotic process. This study aimed to investigate the role of EAT as a marker associated with a higher vulnerability of atheromatous coronary plaques in patients with acute myocardial infarction (AMI) as compared to patients with stable angina. Material and methods: This analysis enrolled a total of 89 patients, 47 with stable angina (SA) and 42 with AMI, who underwent echocardiographic investigations and epicardial fat measurement in 2D-parasternal long axis view. The study lot was divided as follows: Group 1 included patients with prior AMI, and Group 2 included patients with SA. Results: There were no significant differences between the two groups regarding cardiovascular risk factors, excepting smoking status, which was recorded more frequently in Group 1 as compared to Group 2 (36.17% vs. 11.63%, p = 0.02). The mean epicardial fat diameter was 9.12 ± 2.28 mm (95% CI: 8.45–9.79 mm) in Group 1 and 6.30 ± 2.03 mm (95% CI: 5.675–6.93 mm) in Group 2, the difference being highly significant statistically (p <0.0001). The mean value of left ventricular ejection fraction was significantly lower in patients with AMI (Group 1 – 47.60% ± 7.96 vs. Group 2 – 51.23% ± 9.05, p = 0.04). EAT thickness values showed a weak but significant positive correlation with the level of total cholesterol (r = −0.22, p = 0.03) and with the value of end-systolic left ventricle diameter (r = 0.33, = 0.001). Conclusions: The increased thickness of EAT was associated with other serum- or image-based biomarkers of disease severity, such as the left ventricular ejection fraction, end-systolic diameter of the left ventricle, and total cholesterol. Our results indicate that EAT is significantly higher in patients with acute coronary syndrome, proving that EAT could serve as a marker of vulnerability in cardiovascular diseases.

P3437Impact of epicardial adipose tissue on global longitudinal strain: a study in patients with normal left ventricular ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Maimaituxun ◽  
K.E.N.Y.A Kusunose ◽  
D.A.I.J.U Fukuda ◽  
S Yagi ◽  
Y Torii ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Regression Analysis ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Epicardial Adipose Tissue ◽  
Left Ventricular ◽  
Male Gender ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Normal Left Ventricular

Abstract Background Epicardial adipose tissue (EAT) locates anatomically and functionally contiguous to the myocardium and coronary arteries. It has been suggested that EAT accumulation is associated with cardiac remodeling and impaired cardiac performance. However, its role in left ventricular (LV) wall strain remains unclear. Purpose In this study, we aimed to clarify: whether EAT accumulation is related to global longitudinal (GLS), circumferential (CS) and radial strain (RS); and if so, in which extent or by which amount of EAT are required to deteriorate these strain. Methods Total 180 patients who had no obstructive coronary artery disease (CAD) on multi-detector computed tomography (MDCT) coronary angiography and normal left ventricular ejection fraction (LVEF) on conventional echocardiography were recruited. Cardiac CT was used to quantify EAT volume (EATV) and echocardiographic speckle tracking was used to measure the GLS, CS and RS. EATV index (EATV/Body surface area) was determined as: EAT volume, the sum of the EAT area from the base to the apex of the heart (cm3)/body surface area (m2). Adipose tissue was determined as the density range between −190 and −30 Hounsfield unit. According to the median value (68 cm3/m2), patients were divided into lower and higher EATV index two groups. Results In higher EATV index group (95±19 cm3/m2), mean age, body mass index (BMI), prevalence of hyperlipidemia and prevalence of CAD were larger than in lower EATV index group (48±14 cm3/m2). Male gender, hypertension, diabetes, smoking and LV mass index were comparable between two groups. Patients in higher EATV index had lower GLS than those in lower EATV index (−19.4±1.2% vs. −18.8±1.3%, p=0.002). However, there were no significant difference between two groups regarding to the CS and RS. Linear regression analysis showed that there was strong correlation between EATV index and GLS (R=0.216, p=0.004); whereas, both RS and CS were strongly associated with the interventricular septum thickness (RS: R=0.248, p=0.003; CS: R= −0.192, p=0.023) and relative wall thickness (RS: R=0.178, p=0.036; CS: R= −0.184, p=0.030) but not with EATV; on multiple regression analysis, EATV was a predictor of GLS independent of age, male gender, BMI, diabetes, hyperlipidemia, hypertension and CAD (Adjusted R2=0.238, p<0.001). Conclusion EATV is independently associated with GLS despite the preserved LVEF and lacking of obstructive CAD, and may play a significant role in estimating impaired longitudinal LV performance.

scholarly journals Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction

2021 ◽  
Vol 7 ◽  
Author(s):  
Gulinu Maimaituxun ◽  
Kenya Kusunose ◽  
Hirotsugu Yamada ◽  
Daiju Fukuda ◽  
Shusuke Yagi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Coronary Artery ◽  
Ejection Fraction ◽  
Longitudinal Strain ◽  
Epicardial Adipose Tissue ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Group Frequency

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function.Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%.Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116–117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects.Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

3D bioprinting for enhanced vascularization, and gene editing to provide a more favorable immunological response are just some of the potential uses of carbon materials

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Large Scale ◽  
Gene Editing ◽  
Cardiac Development ◽  
Immunological Response ◽  
Extended Period ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
3D Bioprinting ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues

While there are still a number of difficulties to overcome when it comes to practical use of large-scale tissue-engineered cardiac structures, there are some intriguing avenues to examine. Carbon is being employed in a number of fields to help solve various aspects of biological integration, biochemical and mechanical signals in cardiac development, 3D bioprinting for enhanced vascularization, and gene editing to provide a more favorable immunological response, to name a few. Clinical trials are particularly crucial when tissue-engineered cardiac tissues are utilized more broadly, since the design and execution of clinical studies will influence the findings in other research. To assess the most appropriate study endpoints, methods such as cardiac MRI with a high degree of reproducibility to measure surrogate markers of left ventricular ejection fraction and myocardial remodeling, as well as inclusion of multiple end points including biomarkers and quality of life metrics, should be evaluated. Furthermore, in order to determine a specific endpoint for morbidity and mortality, studies must include follow-up over an extended period of time.

Abstract 542: Chronic Doxorubicin Cardiotoxicity Assessed in Engineered Cardiac Tissues Generated in Biowire™ II Platform

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Roozbeh Aschar-sobbi ◽  
Julia E Napolitano ◽  
Danielle R Bogdanowicz ◽  
Michael P Graziano
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Resting Membrane Potential ◽  
Ventricular Ejection Fraction ◽  
Cardiac Tissues

The anthracycline doxorubicin is an effective anti-tumor agent widely used in both adults and children. One major adverse effect of doxorubicin therapy is dose-dependent cardiotoxicity, ranging from asymptomatic reduction in left ventricular ejection fraction to more serious, potentially fatal symptoms including arrythmias and congestive heart failure. The exact mechanism of doxorubicin-induced cardiotoxicity remains unknown. Recently, human induced pluripotent stem cells (hiPSC) have emerged as a potential tool to model cardiac toxicity, but their fetal-like phenotype raises concerns about the translatability of in vitro data to in vivo cardiotoxicity. To overcome this limitation, Biowire™ II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-derived cardiomyocytes and human cardiac fibroblasts. Using long-term electrical stimulation, ECTs with a phenotype approaching that of adult human myocardium were obtained. The ECTs were then exposed to 1 μM doxorubicin for 8 days followed by 7 days of washout. Measurements of contractile force amplitude at 1 Hz stimulation showed a transient increase in force within 24 hours of doxorubicin exposure followed by decrease in force after 2 days. Intracellular recordings of action potential (AP) showed a decrease in maximum upstroke velocity (dV/dt), AP amplitude (APA), and resting membrane potential (RMP) after 8 days of doxorubicin treatment. In addition, action potential duration (APD) at 30% (APD30) repolarization was increased in doxorubicin-treated ECTs, whereas APD50 and APD90 were decreased. Following 7 days of washout, no difference in force or AP parameters was found between doxorubicin and vehicle-treated ECTs with the exception of APD50 and APD90 which remained abbreviated. A global untargeted analysis of the conditioned media from doxorubicin-treated ECTs identified 204 analytes and revealed an upregulation of redox homeostasis, differential fatty acid metabolism, altered glycolysis and TCA cycle metabolites, and decreased nucleoside metabolism compared to vehicle-treated ECTs. These results show that doxorubicin not only increases oxidative stress, but also irreversibly affects action potential duration which may predispose to cardiac arrhythmias.

scholarly journals Macrophage Accumulation and Angiogenesis in Epicardial Adipose Tissue in Cardiac Patients with or without Chronic Heart Failure

2020 ◽  
Vol 10 (17) ◽  
pp. 5871
Author(s):  
Doina Butcovan ◽  
Veronica Mocanu ◽  
Daniel V. Timofte ◽  
Victor V. Costan ◽  
Radu Danila ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Chronic Heart Failure ◽  
Epicardial Adipose Tissue ◽  
Left Ventricular ◽  
Epicardial Fat ◽  
Right Atrial ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Routinely measuring epicardial fat had become a novel tool for cardiovascular risk stratification. Structural changes in epicardial adipose tissue (EAT), including fat thickness, inflammation, and angiogenesis, have been described in coronary artery disease (CAD) patients. We proposed to measure EAT thickness and characterize inflammatory infiltrate and angiogenesis in epicardial adipose tissue in CAD patients with and without chronic heart failure (CHF), established by cardiac dysfunction on echocardiography (left ventricular ejection fraction, LVEF ≤ 50%) and symptoms of heart failure (New York Heart Association (NYHA) functional class II or III).The study included 15 patients with CAD (demonstrated by coronary angiography),, who underwent right atrial appendages (RAA) excision during coronary artery bypass graft (CABG). The study was performed by histopathological, immunohistochemical (IHC), and morphometrical analysis. EAT thickness was assessed by using morphometry applied on routine histological stains. Inflammatory cell infiltration and angiogenesis were investigated immunohistochemically by using antibodies against CD68 and CD34 markers. Diminished EAT thickness in the CAD patients with CHF was associated with increased macrophage infiltration and reduced angiogenesis of the EAT as compared to CAD patients without CHF. In conclusion, the present study on epicardial fat samples of the RAA suggested that high expression of CD68 appeared to be associated with severe deterioration of heart function in CAD patients who underwent myocardial revascularization consisting of CABG.

scholarly journals Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e017187 ◽  
Author(s):  
Paloma Gastelurrutia ◽  
Carolina Gálvez-Montón ◽  
Maria Luisa Cámara ◽  
Juan Bustamante-Munguira ◽  
Pablo García-Pavia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adipose Tissue ◽  
Bypass Graft ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Link Type ◽  
Standard Clinical Practice ◽  
Pericardial Adipose Tissue ◽  
Randomised Controlled

IntroductionCardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial.Study designThe AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days.Ethics and disseminationThe institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings.Trial registration numberClinicalTrials.gov:NCT02798276, pre-results.

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