scholarly journals Cellular Prion Protein Is Essential for Myocardial Regeneration but Not the Recovery of Left Ventricular Function from Apical Ballooning

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 167
Author(s):  
Jiunn-Jye Sheu ◽  
Han-Tan Chai ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
Yi-Ling Chen ◽  
...  

This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Cheuk-Kwan Sun ◽  
Yen-Yi Zhen ◽  
Hung-I Lu ◽  
Pei-Hsun Sung ◽  
Li-Teh Chang ◽  
...  

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hon Kan Yip ◽  
Tzu -Hsien Tsai ◽  
Steve Leu ◽  
Sarah Chua

Background: We tested the hypothesis that mitochondria-replacement therapy ameliorated 100% oxygen-induced rat acute respiratory distress syndrome (ARDS). Methods and Results: Adult-Male SD rats (n=24) were equally categorized into group 1 (controls, room air inhalation), group 2 (ARDS: induced by inhalation of 100% oxygen for 48 hrs), and group 3 [ARDS + mitochondrial transfusion (1400 μg/each rat) from intra-venous administration 6 h after ARDS induction]. By 72 h after ARDS induction, the oxygen saturation (O 2 -Sat) was significantly lower in group 3 and more significantly lower in group 2 than in group 1, whereas pulmonary artery systolic-blood pressure showed a reversed pattern of O 2 -Sat among three groups (all p<0.001). H&E stain for lung crowded score showed an identical pattern of O 2 -Sat and number of alveolar sacs and lung weight exhibited an opposite pattern of O 2 -Sat among the three groups. The protein expressions of apoptotic (mitochondrial Bax, cleaved caspase 3 & PARP), fibrotic (Smad5, TGF-β), ROS (NOX-1, NOX-2, NOX-4), oxidative stress (oxidized protein), DNA- & mitochondrial-damaged (γ-H2AX, Ki-67; cytosolic cytochrome-c) and inflammatory (TNF-α, MMP-9, NF-κB) biomarkers, and IHC/IF microscopic findings of inflammatory (CD14+, CD68+), DNA-damaged (γ-H2AX+, Ki-67+) cells exhibited an opposite pattern, whereas the protein expressions of anti-apoptotic (Smad1/3, BMP-2) markers exhibited an identical pattern of O 2 -Sat among three groups (all p<0.001). The anti-oxidant (HO-2, NQO-1), mitochondrial-preserved (mitochondrial cytochrome-c) biomarkers, and cellular levels of anti-oxidants (HO-1, NQO-1, GR, GPx) were significantly higher in group 2 and more significantly higher in group 3 than in group 1 (all p<0.0001). Conclusions: Mitochondria therapy protects against 100% oxygen-induced ARDS. Key words: mitochondrial replacement, acute lung injury, inflammation, oxidative stress, DNA and mitochondrial damage


2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Tsung-Cheng Yin ◽  
Christopher Glenn Wallace ◽  
Kuan-Hung Chen ◽  
Pei-Lin Shao ◽  
...  

This study tested the hypothesis that extracorporeal shock wave- (ECSW-) assisted adipose-derived stromal vascular fraction (SVF) therapy could preserve left ventricular ejection fraction (LVEF) and inhibit LV remodeling in a rat after acute myocardial infarction (AMI). Adult male SD rats were categorized into group 1 (sham control), group 2 (AMI induced by left coronary artery ligation), group 3 [AMI + ECSW (280 impulses at 0.1 mJ/mm2, applied to the chest wall at 3 h, days 3 and 7 after AMI), group 4 [AMI + SVF (1.2 × 106) implanted into the infarct area at 3 h after AMI], and group 5 (AMI + ECSW-SVF). In vitro, SVF protected H9C2 cells against menadione-induced mitochondrial damage and increased fluorescent intensity of mitochondria in nuclei (p<0.01). By day 42 after AMI, LVEF was highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, and similar between the latter two groups (all p<0.0001). LV remodeling and infarcted, fibrotic, and collagen deposition areas as well as apoptotic nuclei exhibited an opposite pattern to LVEF among the groups (all p<0.0001). Protein expressions of CD31/vWF/eNOS/PGC-1α/α-MHC/mitochondrial cytochrome C exhibited an identical pattern, whilst protein expressions of MMP-9/TNF-α/IL-1β/NF-κB/caspase-3/PARP/Samd3/TGF-β/NOX-1/NOX-2/oxidized protein/β-MHC/BNP exhibited an opposite pattern to LVEF among five groups (all p<0.0001). Cellular expressions of CXCR4/SDF-1α/Sca-1/c-Kit significantly and progressively increased from groups 1 to 5 (all p<0.0001). Cellular expression of γ-H2AX/CD68 displayed an opposite pattern to LVEF among the five groups (all p<0.0001). In conclusion, ECSW-SVF therapy effectively preserved LVEF and inhibited LV remodeling in rat AMI.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.


2019 ◽  
Vol 71 (1) ◽  
Author(s):  
Mohamed MesbahTahaHassanin ◽  
Ahmad ShafieAmmar ◽  
Radwa M. Abdullah ◽  
Mohammad Hassan Khedr

Abstract Background Right ventricular apical pacing with the resultant left ventricular dyssynchrony often leads to depressed systolic function and heart failure. This study aimed at investigating the relation between various septal locations guided by ECG and fluoroscopy and the intermediate term functional capacity of the patients. Results Fifty patients who received a single lead pacemaker with assumed > 90% pacemaker dependency. Patients were randomized according to RV pacing site RV into group 1 “high septum” (n = 15), group 2 “mid septum” (n = 25), and group 3 “low septum” (n = 10) using QRS vector and duration as well as fluoroscopic parameters. Their clinical status was assessed 6 months after device implementation using 6-min walk test (6MWT). The study showed that paced QRS complex duration itself has no significant difference between the different septal pacing locations (P-value 0.675), although its combination with the paced QRS complex vector can signify the optimal pacing site and 6MWT showed a significant difference among the groups in favor of group 1; group 1 (413.3 ± 148.5), group 2 (359.8 ± 124.6), and group 3 (276.0 ± 98.5) P value 0.04. Conclusion There was a significant difference found between the three septal pacing sites concerning the patient functional capacity with superiority of high septal location. By contrast, different septal sites showed no significant difference of the paced QRS complex duration. To optimize the pacing site in the septum, assessment of the paced QRS vector in leads I and III is of a great benefit especially when combined with paced QRS complex duration assessment.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sergio Barros-Gomes ◽  
Patricia A Pellikka ◽  
Angela Dispenzieri ◽  
Hector R Villarraga

Introduction: Diastolic dysfunction has been characterized in relation to the relaxation and compliance properties of the left ventricle; limited information exists regarding its relationship to systolic function as assessed by deformation imaging. Objectives: To determine if there is left ventricular systolic dysfunction detected by global longitudinal strain (GLS) measured by two dimensional speckle tracking echocardiography in patients with immunoglobulin light chain (AL) amyloidosis with different degrees of diastolic dysfunction and normal ejection fraction (EF). Methods: Consecutive biopsy-proven AL patients with preserved EF (≥ 55%) who had a comprehensive echocardiogram performed and strain analysis were included. Cohort was divided into 5 groups according to the different grades of diastolic dysfunction: Group 0: normal filling pressures; Group 1: abnormal relaxation; Group 2: pseudo-normal pattern; Group 3: reversible restrictive; Group 4: fixed restrictive. Images were acquired and performed on a Vivid 9 from the 3 apical views, and analyzed on vendor-specific software (Echo-PAC, GE). GLS was averaged from the 16 segments, and their means compared by ANOVA and each pair with Student’s t test. Results: A total of 858 patients were included, mean age was 63.7 years ± 10.1, and 61.5% were male. From those, 205 (24%) were in group 0; 299 (35%) in group 1; 255 (30%) in group 2; 65 (7%) in group 3; and 34 in group 4 (4%). GLS means measurements were -18.95 ± 2.4, -16.86 ± 3.4, -15.60 ± 3.9, -12.31 ± 3.0, and -10.48 ± 3.3, respectively (P<0.0001). All individual GLS values were significantly different statistically when compared between each group (P<0.01 for all pairs; figure). Conclusions: Longitudinal systolic mechanical function is progressively impaired in AL amyloid patients as diastolic dysfunction progresses, despite normal EF. This systolic dysfunction provides insights into the intrinsic relationship between the components of the cardiac cycle.


2016 ◽  
Vol 3 (3) ◽  
pp. 138-141
Author(s):  
O. Onikiienko

Data of echocardiographic characteristics of 59 children 10-11 years old, involved in football is presented in article. Depending on the duration of sports activities the children were divided into 3 groups: group 1 - children who play football up to 3 years (24 children), Group 2 - children who play football from 3 to 5 years (23 children), Group 3 - training duration over 5 years (12 children). It was found that the linear sizes of the heart were not significantly different in the groups studied, which may indicate that myocardial remodeling as cardiac adaptation to sporting loads takes more time. It was revealed that more trained children (group 3) have significantly higher left ventricular ejection fraction compared with group 1 (p = 0.05) and Group 2 (p = 0.0051). Keywords: athletes, children, echocardiography РезюмеО. ОникиенкоДвумерные эхокардиографические характеристики препубертатных спортсменов В статье приведены результаты ультразвукового обследования 59 детей 10-11 лет, занимающихся футболом. В зависимости от длительности занятий спортом дети были разделены на 3 группы: группа 1 – дети со стажем до 3 лет (24 ребенка), группа 2  - стаж занятий от 3 до 5 лет (23 ребенка), группа 3 – стаж занятий более 5 лет (12 детей). Установлено, что линейные размеры сердца достоверно не отличались в группах обследованных, что может свидетельствовать о более длительном процессе ремоделирования миокарда как адаптации сердца к спортивным нагрузкам. Выявлено, что у более тренированных детей (группа 3) достоверно выше фракция выброса левого желудочка по сравнению с группой 1 (p = 0.05) и с группой 2 (p = 0.0051). Ключевые слова: спортсмены, дети, эхокардиография   РезюмеО. ОнікієнкоДвовимірні ехокардіографічні характеристики препубертатних спортсменівУ статті наведено результати ультразвукового обстеження 59 дітей 10-11 років, які займаються футболом. Залежно від тривалості занять спортом діти були розділені на 3 групи: група 1 - діти зі стажем до 3 років (24 дитини), група 2 - стаж занять від 3 до 5 років (23 дитини), група 3 - стаж занять більше 5 років (12 дітей). Встановлено, що лінійні розміри серця достовірно не відрізнялися в групах обстежених, що може свідчити про більшу тривалість ремоделювання міокарда як адаптації серця до спортивних навантажень. Виявлено, що у більш тренованих дітей (група 3) достовірно вища фракція викиду лівого шлуночка в порівнянні з групою 1 (p = 0.05) і з групою 2 (p = 0.0051). Ключові слова: спортсмени, діти, ехокардіографія


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.


2021 ◽  
Author(s):  
Baotao Huang ◽  
Lu Yang ◽  
Bosen Yang ◽  
Fangyang Huang ◽  
Qianfeng Xiao ◽  
...  

Abstract Background and aimsLeft ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. However, little is known about the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD).MethodsIn this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using formulas. Higher body fat was defined as the percentage of body fat was greater than 75th percentile. LVH was defined according to guidelines’ definition. Patients were divided into four groups: group 1, lower body fat and no LVH; group 2, lower body fat and LVH; group 3, higher body fat and no LVH; group 4, higher body fat and LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.ResultsOver 2.2 years, there were 120 deaths. Patients with higher body fat and no LVH (group 3) had similar risk of death (adjusted HR 1.83, 95%CI 1.00-3.38, P = 0.054) compared to the reference group (group 1), while patients with lower body fat and LVH (group 2) had the highest risk (adjusted HR 2.15, 95%CI 1.26–3.64, P = 0.005) of death. The results were robust after different degree of adjustment.ConclusionCertain amount of BF was not associated with increased risk of all-cause death in patients with CAD, even seems protective in those concomitant with LVH.


2018 ◽  
Vol 90 (9) ◽  
pp. 60-67 ◽  
Author(s):  
T E Rudenko ◽  
E S Kamyshova ◽  
M P Vasilyeva ◽  
I N Bobkova ◽  
N I Solomakhina ◽  
...  

Purpose of the study. To examine the frequency and risk factors for the development of diastolic dysfunction (DD) of the left ventricle (LV) of the heart in patients with chronic kidney disease (CKD). Materials and methods. The study included 225 patients with stage I-CKD of non-diabetic etiology (median age 47.0 years, 50.2% of women). Depending on the degree of decrease in the glomerular filtration rate (GFR), all patients were divided into 3 groups. Group 1 (n=70) consisted of patients with GFR 89-45 ml / min / 1.73 m2, group 2 (n=120) - patients with GFR 44-15 ml / min / 1.73 m2, group 3 (n=35) - patients with GFR


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