Effect of infarct stiffness on non-infarcted left and right ventricular tissue remodeling: a computational study based on myocardial mechano-transduction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Koopsen ◽  
N Van Osta ◽  
E Willemen ◽  
F.A Van Nieuwenhoven ◽  
J Gorcsan ◽  
...  
Keyword(s):  
Computational Model ◽  
Computational Study ◽  
Compensatory Hypertrophy ◽  
Funding Source ◽  
Tissue Mass ◽  
Model Simulations ◽  
National Budget ◽  
End Diastolic Volume ◽  
Public Grant ◽  
Infarcted Tissue

Abstract Background/Introduction The mechanical properties of infarcted myocardium are important determinants of cardiac pump function and risk of developing heart failure following myocardial infarction (MI). Purpose To better understand the effects of infarct stiffness on compensatory hypertrophy and dilation of non-infarcted tissue in the left (LV) and right ventricle (RV), by using a computational model. Methods The CircAdapt computational model of the human heart and circulation was applied to simulate an acute MI involving 20% of LV wall mass. The simulation was validated using previously published experimental data. Subsequently, two degrees of increased infarct stiffness were simulated. In all three simulations, a model of structural myocardial adaptation of the non-infarcted tissue was applied, based on sensing of mechanical loading of myocytes and extracellular matrix (ECM). Results Mild and severe stiffening of the infarct reduced the increase of LV end-diastolic volume (EDV) from +23 mL to +17 mL and +16 mL, respectively, and the increase of LV non-infarcted tissue mass from +31% to +21% and +18%. RV EDV decreased after adaptation, and mild and severe infarct stiffening reduced the decrease of RV EDV from −21 mL to −12 mL and −10 mL, respectively. Increase of RV tissue mass was reduced from +13% to +8% and +7% with mild and severe infarct stiffening. In the LV, reduced dilation and hypertrophy were driven mainly by a reduction of maximum stress in the ECM and a higher stress between the myocytes and ECM following infarct stiffening. The decreased RV hypertrophy, but not EDV reduction, was caused by a reduction of maximum RV ECM stress and maximum RV active myofiber stress. Conclusions Model simulations predicted that a stiffened LV infarct reduces both LV and RV non-infarcted tissue hypertrophy as well as LV dilation. In LV remodeling, maximum ECM stress and stress between myocyte and ECM played a more prominent role than in RV remodeling, while maximum active stress was more important in the RV. Overview of all model simulations Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

scholarly journals Quantitative 4D Flow CMR analysis of intracardiac blood flow energetics in ischemic cardiomyopathy patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Riva ◽  
A Camporeale ◽  
F Sturla ◽  
S Pica ◽  
L Tondi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Cardiomyopathy ◽  
Inverse Correlation ◽  
Lv Function ◽  
Funding Source ◽  
4D Flow ◽  
Anterior Myocardial Infarction ◽  
National Budget ◽  
4D Flow Cmr ◽  
Public Grant

Abstract Background Ischemic cardiomyopathy (ICM) is often associated with negative LV remodelling after myocardial infarction, sometimes resulting in impaired LV function and dilation (iDCM). 4D Flow CMR has been recently exploited to assess intracardiac hemodynamic changes in presence of LV remodelling. Purpose To quantify 4D Flow intracardiac kinetic energy (KE) and viscous energy loss (EL) and investigate their relation with LV dysfunction and remodelling. Methods Patients with prior anterior myocardial infarction underwent a CMR study with 4D Flow sequences acquisition; they were divided into ICM (n=10) and iDCM (n=10, EDV>208 ml and EF<40%). 10 controls were used for comparison. LV was semi-automatically segmented using short axis CMR stacks and co-registered with 4D Flow. Global KE and EL were computed over the cardiac cycle. NT-proBNP measurements were correlated with average and peak values, during systole and diastole. Results Both LV volume and EF significantly differ (P<0.0001) between iDCM (EDV=294±56 ml, EF=24±8%), ICM (EDV=181±32 ml, EF=34±6%) and controls (EDV=124±29 ml, EF=72±5%). If compared to controls, both ICM and iDCM showed significantly lower KE (P≤0.0008); though lower than controls, EL was higher in iDCM than ICM. Within the iDCM subgroup, diastolic mean KE and peak EL reported good inverse correlation with NT-proBNP (r=−0.75 and r=−0.69, respectively). EL indexed (ELI) to average KE during systole was higher in the entire ischemic group as compared to controls (ELI(ischemic) = 0.17 vs. ELI(controls) = 0.10, P=0.0054). Conclusions 4D Flow analyses effectively mapped post-ischemic LV energetic changes, highlighting the disproportionate intraventricular EL relative to produced KE; preliminary good correlation between LV energetic changes and NT-proBNP will deserve further investigation in order to contribute to early detection of heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

Is there an exercise duration threshold for exercise-induced troponin elevation in healthy recreational athletes? The NEEDED 2014 advanced heart rate monitor substudy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Bjorkavoll-Bergseth ◽  
B Auestad ◽  
O Kleiven ◽  
O Skadberg ◽  
T Eftestol ◽  
...  
Keyword(s):  
Heart Rate ◽  
Clinical Status ◽  
Exercise Duration ◽  
Strenuous Exercise ◽  
Clinical Consequence ◽  
Funding Source ◽  
Recreational Athletes ◽  
National Budget ◽  
Exercise Induced ◽  
Public Grant

Abstract Background/Introduction Following prolonged strenuous exercise there is an exercise-induced troponin (cTn) elevation in healthy individuals. The precise mechanisms and clinical consequence of this cTn elevation remain to be determined. It has recently been demonstrated that exercise intensity, exceeding a heart rate (HR) of 150 bpm, is correlated with exercise-induced cTn elevation. Purpose The present work aims to determine if there is a threshold for exercise duration with a HR exceeding 150 bpm associated with an excessive exercise-induced cTn elevation. Methods A total of 177 healthy subjects were included in the present analysis of HR data obtained from sport watches used during a 91-km recreational mountain bike cycle race. Clinical status, cTnI, ECGs, blood pressure and demographics were obtained 24 h prior to- and at 3 h and 24 h after the race. Results are reported as median and 25th and 75th percentile. We used Tree regression to determine the association between elevated cTnI and exercise duration exceeding a HR of 150 bpm. Results Subjects were 82% (n=146) males, 44 (39–51) years, with a race time of 3.5 (3.1–3.9) h. Baseline cTnI was 1.9 (1.6–3.3) ng/L. There was a cTnI elevation in all study participants at 3 h, cTnI: 60.0 (36.0–99.3) ng/L, with a significant (p<0.001) reduction at 24 hours following exercise, cTnI: 10.9 (6.1–22.4) ng/L. Tree regression identified 168 min of exercise, with a HR exceeding 150 bpm, to be associated with an excessive increase in cTnI both at 3 h, and at 24 h following the race (figure). The median cTn values above and below the threshold are presented in the Table. Conclusion The present analysis suggests that exceeding a specific duration of high intensity exercise may be associated with excessive cTn elevation in susceptible individuals. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Health authoritites.

scholarly journals Distinguishing sinus rhythm from atrial fibrillation on single-lead ECGs using a deep neural network

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oudkerk Pool ◽  
B.D De Vos ◽  
J.M Wolterink ◽  
S Blok ◽  
M.J Schuuring ◽  
...  
Keyword(s):  
Neural Network ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Roc Curve ◽  
Model Development ◽  
Independent Set ◽  
Funding Source ◽  
National Budget ◽  
Validation Set ◽  
Public Grant

Abstract Background The growing availability of mobile phones increases the popularity of portable telemonitoring devices. An atrial fibrillation diagnosis can be reached with a recording of 30s on such telemonitoring devices. However, current commercially available automatic algorithms still require approval by experts. Purpose In this research we aimed to build an artificial intelligence (AI) algorithm to improve automatic distinction of atrial fibrillation (AF) from sinus rhythm (SR), to ultimately save time, costs, and to facilitate telemonitoring programs. Methods We developed a deep convolutional neural network (CNN), based on a residual neural network (ResNet), tailored to single-lead ECG analysis. The CNN was trained using publicly available single-lead ECGs from the 2017 PhysioNet/ Computing in Cardiology Challenge. This dataset consists of 60% SR, 9% AF, 30% alternative rhythm, and 1% noise ECGs. The 8528 available ECGs were divided into a training (90%) and validation set (10%) for model development and hyperparameter optimization. Results The trained CNN was applied to an independent set containing single-lead ECGs of 600 patients equally divided into two groups: SR and AF. Both groups comprised of 300 unique ECGs (SR; 60% male, 63±11 years, AF; 38% male, 56±14 years). In distinguishing between AF and SR, the method achieved an accuracy of 0.92, an F1-score of 0.91, and area under the ROC-curve of 0.98. Conclusion The results demonstrate that distinguishing SR and AF by a fully automatic AI algorithm is feasible. This approach has the potential to reduce cost by minimizing expert supervision, especially when extending the algorithm to other heart rhythms, like premature atrial/ventricular contractions and atrial flutter. Figure 1. ROC curve Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dekkerbeurs - Hartstichting

scholarly journals The clinical atlas of cardiomyopathies: data from the prospective DZHK TORCH study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Sedaghat-Hamedani ◽  
J Trebing ◽  
A Kindermann ◽  
E Kayvanpour ◽  
K Tan ◽  
...  
Keyword(s):  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Left Ventricular ◽  
Favourable Outcome ◽  
Funding Source ◽  
Icd Implantation ◽  
Cardiovascular Research ◽  
National Budget ◽  
Public Grant ◽  
High Level

Abstract Introduction Cardiomyopathies (CMPs) are leading causes of heart failure (HF) and sudden cardiac death (SCD). Comparative data of the multiple cardiomyopathy forms are largely missing. The TranslatiOnal Registry for CardiomyopatHies (TORCH) is the largest prospective multicentre CMP registry world-wide. Enrolled patients are comprehensively phenotyped by clinical examinations, state-of-the-art imaging, and molecular investigations. In this study, we present the baseline and 1-year follow-up data. Methods TORCH is a national, prospective, multicentre registry within the German Centre for Cardiovascular Research (DZHK) and includes 2300 patients with non-ischemic (primary and secondary) CMP from 20 centres. The minimum follow up was one year. The DZHK-wide harmonization of datasets and SOPs ensure a high level of data quality and comparability across different CMP forms. Results Dilated cardiomyopathy (DCM) has the highest prevalence with 64% of all enrolled patients, followed by hypertrophic cardiomyopathy (HCM) with 16%. At baseline, patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) were treated more often with ICD implantation and showed high rates of adequate ICD therapies (65.8%, p<0.05 and 47.8%, p<0.05, respectively). The prevalence of stroke or transient ischemic attack (TIA) was in multivariate analysis significantly higher (p<0.05) in left ventricular non-compaction cardiomyopathy (LVNC, 14.9%), while atrial fibrillation was lower than in other cardiomyopathy forms. Patients with amyloidosis had the worst outcome (HR: 6; 95% CI: 2.5–14.5, P<0.05) with annual mortality of >15% and 12% receiving heart transplantation. In DCM, reverse remodelling with improvement of functional parameters and biomarkers was more often observed in idiopathic and inflammatory cases compared to familial ones. HCM patients had the most favourable outcome. Conclusion and outlook TORCH is the largest prospective study focusing on CMPs. We provided for the first time prospectively the clinical data of patients with diverse cardiomyopathies with outcome. Furthermore, comparing the different CMP forms on the clinical and molecular level will be an important step to enable translational research projects. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research (DZHK)

Impact of pre-hospital resuscitation on short-and long-term mortality in patients with cardiogenic shock and multivessel disease. Results of the CULPRIT trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
U Zeymer ◽  
B Alushi ◽  
A Lauten ◽  
I Akin ◽  
S Desch ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiogenic Shock ◽  
Coronary Intervention ◽  
Funding Source ◽  
National Budget ◽  
Cardio Pulmonary Resuscitation ◽  
Percutaneous Coronary ◽  
Public Grant ◽  
The Impact

Abstract Background There are only a few prospective data on the outcome of patients with cardio-pulmonary resuscitation (CPR) admitted with acute myocardial infarction (AMI) complicated by cardiogenic shock and an invasive strategy including primary percutaneous coronary intervention (PCI). Therefore, we evaluated the impact of pre-hospital CPR on outcomes in a large group of patients with AMI complicated by cardiogenic shock. Methods We used the data of the prospective CULPRIT-Shock trial and registry and including patients with acute myocardial infarction complicated by cardiogenic shock. The primary endpoint was 30-day mortality or renal replacement therapy. Results Between 2013 and 2017, a total of 1055 patients were included in the randomized trial (n=686) and in the registry (n=369), 550 (54%) had CPR, 40 had no information regarding CPR. Baseline characteristics, procedural features and outcomes in the two groups with and without CPR are given in the table. Conclusion Patients with pre-hospital CPR represent more than half of the population with AMI complicated by cardiogenic shock. They are younger, have less risk factors and more often LAD as infarct vessel. Despite the younger age and a high success rate of PCI patients with CPR have a high 30-day mortality. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsches Zentrum fuer Herz-Kreislauf-Forschung - DZHK

A novel trigger-substrate mechanism based on clinically concealed repolarization abnormalities underlies idiopathic ventricular fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Cluitmans ◽  
L Bear ◽  
U Nguyen ◽  
B Van Rees ◽  
J Stoks ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Sudden Cardiac Arrest ◽  
Funding Source ◽  
Drug Infusion ◽  
National Budget ◽  
Coupling Interval ◽  
Temporal Coupling ◽  
Structural Disease ◽  
Public Grant ◽  
Repolarization Abnormalities

Abstract Background Sudden cardiac arrest (SCA) is most often due to ventricular fibrillation (VF). When no cause is found during diagnostic follow-up, fibrillation is classified as idiopathic (iVF). We hypothesize that a critical functional substrate-trigger interaction underlies iVF. Purpose To study electrophysiological triggers and substrate for iVF in a clinical cohort; and seek mechanistic explanations in explanted pig hearts and computer models mimicking trigger-substrate interactions. Methods Repolarization time (RT) isochrones on the epicardium were studied with electrocardiographic imaging (ECGI) in patients with iVF, patients with frequent monomorphic premature ventricular complexes (fmPVC) but no structural disease or SCA, and controls without cardiovascular disease. RT gradients were created in explanted, Langendorff-perfused pig hearts by local infusion of dofetilide (“dof”, 250 nM, delaying RT) and pinacidil (“pin”, 30 μM, shortening RT) in adjacent regions of the heart. Arrhythmia inducibility was tested by programmed stimulation (8 atrial stimuli [S1] followed by one ventricular stimulus [S2] paced at regions of early or late RT). A computational ventricular monodomain model was used to study the location-dependency of trigger-substrate interaction; RT gradients were created by local changes in potassium channel conductance. Results Although QTc values were similar, iVF survivors (n=11) displayed significantly steeper RT gradients than controls (n=10) or fmPVC individuals (n=7): 269±111 vs 179±40 vs 171±76 ms/cm respectively (panel A). Unipolar electrograms (EGMs) at the gradients displayed a change in polarity of the local T wave (B). In iVF, PVCs originated more often from regions with early RT than in fmPVC individuals (yellow circles in A; 64% vs 14%). In the explanted hearts (C), drug infusion resulted in similar RT gradients and polarity changes of EGM T waves (D-E). VF inducibility by pacing of the early RT region (D) increased significantly with steeper RT gradients (baseline: 3/6 hearts inducible, dof+pin: 3/3). Pacing of late RT regions (E) did not induce arrhythmias in baseline (0/6) nor with RT gradients (0/3). For similar pacing intervals at the early RT region, the 12-lead ECG R-on-T morphology was similar but VF only occurred in the presence of RT gradients (F). In the computer model, the number of inducible pacing intervals critically depended on the stimulus location (G). Conclusion Combined, these results demonstrate that R-on-T superposition per se is insufficient to explain arrhythmogenesis. Rather, not only the temporal coupling interval but also the spatial origin of PVCs in relationship to the degree of local repolarization abnormalities are critical elements. In iVF, a substrate of RT gradients (panel H1) with triggers from early RT regions (H2) precipitate reentry (H3). Noninvasive ECGI can uncover these substrate and trigger characteristics in (at least a subset of) iVF survivors. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Scientific Research Veni grant TTW 16772, French National Research Agency (ANR-10-IAHU04-LIRYC)

scholarly journals Transcatheter intervention of coarctation of the aorta (CoA): a multinational population-based registry – effect on hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Eriksson ◽  
J Pihkala ◽  
A.S Jensen ◽  
G Dohlen ◽  
P Liuba ◽  
...  
Keyword(s):  
Pharmacological Treatment ◽  
Coarctation Of The Aorta ◽  
Life Time ◽  
Population Based ◽  
Funding Source ◽  
Transcatheter Intervention ◽  
National Budget ◽  
Need For Treatment ◽  
Public Grant

Abstract Background CoA is associated with hypertension caused by reduced wind kessel function in the aortic arch, general hypoplasia of the arch and/or essential hypertension. In patients with a native or recurrent/rest CoA, a gradient >20 mmHg by non-invasive meassurement if associated with hypertension is an ESCguideline indication for intervention. We studied the persistence and presence of hypertension after transcatheter intervention of a CoA Methods All consecutive patients undergoing catheter interventions for CoA from 1st of January 2000 to 31st of December 2016 were identified by each of the particpating nine centers. The nine centers perform all catheter interventions for CoA for a complete population coverage of 25 millions inhabitants. A common protocoll was filled out from medical records. Hypertension was defined as a pre-intervention blood pressure above 140/80 or pharmacological treatment of hypertension. Exclusion criteria were weight less than 20 kg at the time of intervention or Norwood surgery Results 590 interventions were performed on 520 patients: two interventions n=76, three: n=11, four n=2 and one patient underwent five interventions. Before intervention, 437 (74%) of the patients were hypertensive and 285 were on pharmacologocal treatment; 134 (48%) were treated with one drug, 79 patients (28%) with two drugs, 41 patients (15%) with three drugs and 14 (5%) with four drugs. After the intervention during follow up hypertension was present in 294 patients (50%, p<0.001 vs pre) of whom 270 (46%) were on pharmacological treatment; with one drug, n=128 (48%), two drugs n=93 (34%), three drugs n=34 (13%) or 4 drugs n=7 (3%). Conclusions Catheter intervention of CoA reduced the presence of hypertension significantly from 74% down to 50% but many patients will remain hypertensive and in need for treatment. Life time follow up also after transcatheter CoA intervention seems warranted. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ALF-LUA, Heart and Lung Foundation

Sirtuin 4 contributes to heart failure development by increasing mitochondrial oxidative stress

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Koentges ◽  
E Khan ◽  
S Birkle ◽  
M Hoelscher ◽  
K Pfeil ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Function ◽  
Funding Source ◽  
Lipid Peroxidation Product ◽  
German Research Foundation ◽  
Mitochondrial Oxidative Stress ◽  
Pronounced Increase ◽  
National Budget ◽  
Public Grant

Abstract   Sirtuin 4 (SIRT4) is a mitochondrial NAD+-dependent deacylase which inhibits the oxidation of glucose and fatty acids, and has been implicated in the regulation of oxidative stress. Given the importance of cardiac energy depletion and ROS during heart failure development, we aimed to define the role of SIRT4 in the development of heart failure. Mice with deletion (SIRT4−/−) or overexpression (SIRT4 TG) of SIRT4 were subjected to transverse aortic constriction (TAC) for 12 weeks or underwent sham procedures. Using echocardiography, ejection fraction (EF) was not different between SIRT4 TG and WT mice subjected to sham operations. In contrast, TAC induced a more pronounced decrease in EF (35% vs. 51%; p<0.05), and a more pronounced increase in LV endsystolic diameter (4.5mm vs. 3.6mm; p<0.05) and myocardial fibrosis (2.2-fold; p<0.05) in SIRT4 TG mice compared to WT mice. Myocardial levels of the lipid peroxidation product 4-hydroxynonenal were increased in WT mice following TAC and were synergistically increased in SIRT4 TG mice following TAC (+66% vs. WT TAC; p<0.05). Administration of the mitochondria-targeted antioxidant MitoQ normalized 4-hydroxynonenal levels, markedly attenuated the decline in EF and almost normalized endsystolic LV diameter in SIRT4 TG mice following TAC. Cardiac function and morphology were unaffected in SIRT4−/− mice during normal or increased workload conditions. Thus, while SIRT4 is not required to maintain cardiac function even in response to increased energy demands, increased expression of SIRT4 accelerates the development of heart failure following TAC, at least in part due to increased mitochondrial oxidative stress. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Research Foundation

Effective reflection distance and its association with pressure augmentation index under a variety of acute hemodynamic perturbation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Uemura ◽  
T Nishikawa ◽  
T Kawada ◽  
M Sugimachi
Keyword(s):  
Augmentation Index ◽  
Aortic Pressure ◽  
Clinical Analysis ◽  
Clinical Population ◽  
Funding Source ◽  
National Budget ◽  
Wave Separation ◽  
Anesthetized Dogs ◽  
Public Grant ◽  
First Time

Abstract   Effective reflection distance (ERD), a conceptual distance to a major reflection site from the aortic root, is associated with aging and pressure augmentation index (AIx) in clinical population. However, it is poorly understood how ERD varies and associates with AIx within a subject when the hemodynamic condition is changed extensively by acute pharmacological interventions. Methods In 13 anesthetized dogs, we measured aortic pressure (AP) and flow (AF) and femoral arterial flow (FF). Using AP, AF and FF, ERD based on an arterial model comprising a tube with frequency-dependent load (ERD_TL) was determined as a physiologically valid reference. ERD was also determined by wave separation (ERD_WSA) and pressure-only analyses (ERD_AW). Hemodynamic condition was changed by administrating zatebradine (bradycardic agent), nitroprusside, noradrenaline, dobutamine, and dextran. Results ERD_TL shortened significantly in response to infusion of nitroprusside or dobutamine. ERD_TL was significantly and negatively associated with AIx in multivariate analysis (Figure/Table). Changes in ERD_WSA or ERD_AW, and their association with AIx were not necessarily concordant with those observed in ERD_TL. Conclusion For the first time, we demonstrated that under diverse hemodynamic conditions, ERD_TL can change sensitively, and associates with AIx physiologically. This substantiates importance of tight attention to medication at clinical analysis of wave reflection phenomena. ERD_WSA or ERD_AW may not be a surrogate of ERD_TL. Responses of ERD to drugs Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science (JSPS)

Nur77 deficiency exacerbates cardiac fibrosis after myocardial infarction through promoting endothelial to mesenchymal transition

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Q Qin ◽  
J.H Chen ◽  
J.B Jia ◽  
J.Y Qian ◽  
J.B Ge
Keyword(s):  
Myocardial Infarction ◽  
Nuclear Receptor ◽  
Cardiac Fibrosis ◽  
Vascular Endothelial Cells ◽  
Funding Source ◽  
Orphan Nuclear Receptor ◽  
Mesenchymal Transition ◽  
National Budget ◽  
Endothelial To Mesenchymal Transition ◽  
Public Grant

Abstract Background Cardiac fibrosis is a reparative process after myocardial infarction (MI), which leads to cardiac remodeling and finally heart failure. Endothelial-to-mesenchymal transition (EndMT) is induced after MI and contributes to cardiac fibrosis after MI. Orphan nuclear receptor Nur77 is a key regulator of inflammation, angiogenesis, proliferation, and apoptosis in vascular endothelial cells. Here, we investigated the role of orphan nuclear receptor Nur77 in EndMT and cardiac fibrosis after MI. Methods and results Cardiac fibrosis was induced through MI by ligation of the left anterior descending coronary artery. Results suggested that Nur77 knockout aggravated cardiac dysfunction and cardiac fibrosis 30 days after MI. Moreover, Nur77 deficency resulted in enhanced EndMT as shown by increased expression of FSP-1, SM22α, Snail and decreased expression of PECAM-1 and eNOS compared with WT mice after MI. Then we found overexpression Nur77 in HCAECs significantly inhibited IL-1β and TGFβ2 induced EndMT, as shown by reduced transition to a fibroblast-like phenotype and preserved angiogenesis potential. Mechanistically, we demonstrated that Nur77 downregulated EndMT through inhibiting NF-κB-dependent pathway Conclusion Nur77 plays a role in cardiac fibrosis through inhibition of EndMT, and may be a promising target for therapy of cardiac fibrosis after MI. Nur77 inhibited EndMT Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Sign in / Sign up

Export Citation Format

Share Document