bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOVEL ITACONATE DERIVATIVE ATTENUATES ISOPROTERENOL INDUCED CARDIOTOXICITY IN EXPERIMENTAL ANIMALS: A MOLECULAR PATHWAY INSIGHT
Authors: Sharma Jatin , Arya Ds , Bhatia Jagriti 
Published: May 2024

Objective:
4-octyl itaconate (4-OI) is a potential drug for the treatment of myocardial infarction on account of its potent anti-inflammatory, antioxidant and anti-apoptotic properties. Thus, we hypothesise that 4-OI may attenuate isoproterenol(ISO) induced cardiotoxicity by modulating several molecular pathways in Wistar albino rats.

Design and method:
After getting approval from animal ethics committee(278/IAEC/2021), the experimental work was started. ISO 5mg/kg s.c., was administered daily for 15 days. Adult male rats were randomly divided into 5 groups (n=6): normal control group, ISO control group, treatment control groups. 4-OI was administered i.p. at 3 different doses (2.5,5,10 mg/kg) to rats from day 1 and continued for 15 days along with ISO. On the 16th day, surgery was performed, right carotid artery was cannulated for recording of hemodynamic parameters. Blood was drawn using cardiac puncture and rats were then sacrificed, one portion of the heart was immediately stored in 10% formalin for histopathological evaluation and second portion was kept in -80 degree C for further studies. Serum was stored for biochemical, pro-inflammatory cytokines estimation (TNF, IL-6, IL1 beta) and cardiac injury markers (CKMB, LDH).

Results:
4-OI improved cardiac function and attenuated pathological changes as seen microscopically in the H&E stained heart tissue sections. On ultrastructural evaluation, 4-OI treatment (5, 10mg/kg) groups presented with lesser nuclear condensation and mitochondrial swelling, as compared to the ISO control group. A significant decline in the serum and tissue levels of cardiac injury markers (CK-MB, LDH) and inflammatory markers were observed in 4-OI (5,10mg/kg) treated rats, as compared to ISO control group. Additionally, 4-OI suppressed oxidative stress and apoptosis, along with an increased PPAR-gamma expression. Molecular pathway assessment revealed that at the dose of 10mg/kg, 4-OI reduced the expression of NFkappaB, IKK-beta and enhanced the expression of Nrf-2 and HO-1. On analysis of the inflammatory MAPK pathway, expression of the pro-survival kinase ERK was also increased while JNK and p38 protein expressions were reduced.

Conclusions:
4-OI at a dose of 10mg/kg mitigates myocardial toxicity in ISO treated rats by maintaining morphological structure of heart tissue with oxidative stress profile and reduced inflammation
NEW APPROACH TO DETECT VASCULAR DAMAGE BY MEASURING ARTERIAL STIFFNESS IN A HEMODYNAMIC MANNER
Authors: Khataei Sanam , De Rico Élizabeth , Philibert Émy , Obeid Hasan , Addour Saliha , Fortier Catherine , Agharazii Mohsen 
Published: May 2024

Objective:
Arterial stiffness is a risk factor for cardiovascular disease, largely attributable to vascular aging, but it can be accelerated by certain metabolic conditions, such as diabetes and kidney disease. Pulse wave velocity (PWV) is the conventional measure used to assess arterial stiffness, typically measured in the supine position with mechanical sensors placed on the carotid and on the femoral arteries. Recent advancements allow for the use of photoplethysmographic sensors to obtain finger-to-toe PWV (ftPWV), which can be performed in the sitting position, offering a new way to examine the vascular wall hemodynamically. The aim of this study is to 1) evaluate the impact of postural changes on arterial stiffness and 2) identify the determinants of PWV changes.

Design and method:
Cross-sectional study with a group of patients with kidney disease (eGFR < 60 ml/min) and a control group (eGFR > 60 ml/min). Blood pressure is first measured with an oscillometric device, then the finger-to-toe pulse wave velocity (ftPWV) is obtained using two photoplethysmographic sensors (pOpmetre®). Three measurements are taken in the supine position and then in the sitting position. Subsequently, paired t-test analyses and linear regressions were performed.

Results:
In the control group (n=37, aged 39 ± 18 years, 54% female), ftPWV increased from 6.8 ± 2.2 to 9.6 ± 2.5 m/s (P<0.001) following the postural change. Similarly, in the kidney disease group (n=73, aged 66 ± 14 years, 37% female), ftPWV significantly increased from 11.2 ± 4.7 to 17.8 ± 11.5 m/s (P<0.001). Linear regression analysis indicated that ftPWV in the supine position (ß = 0.336; P<0.001) and the presence of diabetes (ß=0.291; P<0.001) were associated with a greater increase in ftPWV. Age, sex, and cardiovascular diseases did not have a significant impact on the increase in ftPWV.

Conclusions:
These preliminary results show a significant increase in ftPWV following postural change, more so in patients with greater arterial stiffness and those with diabetes. This observation presents an intriguing opportunity to investigate whether a postural change can be used as a vascular stress test to identify arterial stiffness.
PULMONARY HYPERTENSION DOES NOT LIMIT TRANSLATIONAL APPROACHES OF HYPOXIA MEDIATED MYOCARDIAL REGENERATION
Authors: Hoenemann Jan -Niklas , Hoffmann Fabian , Weis Henning , Gerlach Darius , Zaha Vlad G , Sadek Hesham , Reuter Hannes , Baldus Stephan , Splettstoesser Frank , Frede Stilla , Levine Benjamin D , Jordan Jens , Limper Ulrich , Tank Jens 
Published: May 2024

Objective:
In mice, prolonged exposure to severe ambient hypoxia promotes myocardial regeneration suggesting a novel treatment target for patients following myocardial infarction. However, hypoxia-induced pulmonary hypertension and myocardial ischemia are potential risks in human studies. Therefore, we conducted a pilot study in carefully selected patients with left ventricular scars to test the cardiovascular safety of prolonged exposure to severe hypoxia.

Design and method:
At the DLR:envihab facility, we enrolled three male patients with 49-126 months past history of myocardial infarction and one healthy man. Patients had an ejection fraction of 47±7%. We applied incremental ambient hypoxia using nitrogen dilution until alveolar oxygen partial pressure had decreased to 35 mmHg. Then, we maintained atmosphere conditions for 14 days (FiO2=0.095) but added 1% oxygen during the night. We assessed right ventricular function and systolic pulmonary artery pressure at baseline, during hypoxia, and 3 days after recovery in normoxia with transthoracic echocardiography. In venous blood samples, we measured high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and glomerular filtration rate (CystatinC) throughout the study.

Results:
We observed no clinical signs of heart failure throughout the study. Hypoxia increased systolic pulmonary artery pressure, which rapidly normalized during recovery (baseline: 35±3 mmHg hypoxia: 47±9 recovery: 28±1, p=0.029). Tricuspid annular plane systolic excursion was 28±3 mmHg at baseline, 26±1 mmHg in hypoxia, and 29±2 mmHg during recovery (p=0.069). Right ventricular free wall strain -22.4±3.9 mmHg at baseline, -24±5.4 in hypoxia, and -22.7±1.5 during recovery (p=0.84). Glomerular filtration rate was reduced in hypoxia, but recovered at 30 days follow-up. Troponin remained in the reference range throughout the study and NTproBNP was decreased following hypoxia (p=0.047).

Conclusions:
In highly selected patients with left ventricular scars, prolonged severe normobaric hypoxia while eliciting pulmonary hypertension did not lead to right heart failure or myocardial damage. Our study provides important information regarding safety of exposing patients to hypoxia in clinical studies or during activities at high altitude.
LOWER PEAK ATRIAL LONGITUDINAL STRAIN VALUES ARE ASSOCIATED WITH OBESITY AND INSULIN RESISTANCE IN YOUNG PATIENTS WITH HYPERTENSION
Authors: Hawpage Manuli , Ezhova Nadezhda , Shavarova Elena , Bazdyreva Elena , Nazyrova Adilya , Shavarov Andrey , Shkolnikova Ekaterina , Kobalava Zhanna 
Published: May 2024

Objective:
The aim of the study was to compare features of left atrium remodeling in young patients with arterial hypertension (HTN) according to metabolic health status

Design and method:
We enrolled 83 young subjects (23 [21; 25] years, 87% males) with HTN diagnosed with office blood pressure (BP) measurement and 24-hours ambulatory BP monitoring according to ESC guidelines criteria (2018). Patients with diabetes mellitus and cardiovascular diseases were not included. We performed routine clinical examination and lab tests and two-dimensional speckle-tracking echocardiography. Patients were divided in two subgroups according to their relation to median of left atrial reservoir strain (LASr) in general population (Nielsen AB. et al., 2021. doi:10.1093/ehjci/jeab201). We estimated and compared main clinical characteristics of obesity and lipid and carbohydrates metabolism including HOMA-IR and non-insulin-based metabolic scores for insulin resistance in derived subgroups with T-test.

Results:
Groups had similar age, sex and BP structure. Subjects with LASr less than 39,4% (n = 48) had higher body mass index (27,2±5,0 vs 24,1±3,7, p=0,0041), waist circumference (93,4±14,0 vs 83,0±10,7, p=0,001) and waist-to-hips ratio (0,90±0,07 vs 0,84±0,07, p=0,0007). Characteristics of lipid metabolism also varied in 2 groups: in lower LASr subgroup triglycerides concentration was higher (1,53±1,06 vs 0,81±0,28, p=0,0005) and high density lipoproteins (HDL) was lower (1,18±0,28 vs 1,55±0,53, p=0,0003) while there was no significant difference in total cholesterol and low density lipoproteins levels. Fasting glucose and HOMA-IR did not differ between the groups but significant differences were observed for non-insulin-based metabolic scores: in lower LASr group METS-IR, TG/HDL ratio and TyG index were higher (41,6±9,25 vs 33,0±6,4, p<0,0001; 3,38±2,94 vs 1,34±0,68, p=0,0004 and 8,55±0,60 vs 8,02±0,30, p<0,0001, respectively). In reverse stepwise regression model for the general group LASr were independently associated with the level of left ventricular ejection fraction, DBP24h, METS-IR index, while the relationship with the HDL-C, SBP24h, relative wall thickness, E/e’ were lost (METS-IR index and HDL-C were included after checking the collinearity).

Conclusions:
young patients with HTN with lower LASr have worse metabolic status estimated with non-insulin-based metabolic scores and obesity characteristics.
REVIVING HEARTS: A YOUTHFUL PERSPECTIVE ON STEM CELL THERAPY IN HEART FAILURE MANAGEMENT — A RCT META-ANALYSIS
Authors: Greca Elona , Ozair Saleha , Michel George 
Published: May 2024

Objective:
Heart failure is a pervasive global health issue, and novel therapeutic approaches are continually explored to improve patient outcomes. Stem cell therapy has emerged as a promising avenue, offering regenerative potential for damaged cardiac tissue. This meta-analysis aims to comprehensively evaluate the impact of stem cell therapy on heart failure management from a youthful perspective.

Design and method:
A systematic literature search was conducted across major databases, identifying 20 randomized controlled trials (RCTs) published up to September 2021. These RCTs assessed stem cell interventions in heart failure patients. Data extraction and quality assessment were performed, with a specific focus on outcomes such as mortality rates, left ventricular ejection fraction (LVEF), and cardiac biomarkers. Effect sizes were calculated for these outcomes, and heterogeneity was assessed.

Results:
Our meta-analysis, comprising a robust dataset, highlights the substantial and statistically significant positive effect of stem cell therapy on key clinical outcomes. Specifically, stem cell therapy is associated with a significant reduction in all-cause mortality rates, underscoring its potential as a life-saving intervention. Furthermore, improvements in LVEF, a critical indicator of cardiac function, are notable and consistent across studies, reinforcing the therapeutic promise of stem cell treatments. Changes in cardiac biomarkers, such asB-type natriuretic peptide (BNP, also exhibit favourable trends with stem cell therapy, further supporting its efficacy.

Conclusions:
This meta-analysis, driven by a youthful perspective and supported by a substantial dataset, provides compelling and definitive evidence supporting the efficacy of stem cell therapy in improving heart failure outcomes. The findings of this study could have a powerful impact on clinical guidelines, advocating for the inclusion of stem cell therapy as a recommended approach in heart failure management. Future research should continue to explore the nuanced aspects of stem cell interventions to refine treatment strategies and unlock new possibilities in heart failure management.
METABOLIC PATHWAYS OF CARDIAC DYSFUNCTION AFTER PREECLAMPSIA IN TRANSGENIC RAT MODEL
Authors: Frolova Alina , Pixner Lorenz , Haase Nadine , Kedziora Sarah , Müller Dominik N. , Dechend Ralf , Herse Florian , Kräker Kristin 
Published: May 2024

Objective:
Preeclampsia (PE), the most common pregnancy disease, is the main cause for maternal and fetal mortality and morbidity worldwide. It is characterized by a sudden increase in blood pressure in combination with signs of end organ damage, e.g. proteinuria. The mechanisms how pathological pregnancy leads to future cardiovascular morbidity are poorly understood. There are number of risk factors shared between PE and cardiovascular disease such as endothelial dysfunction, obesity, hypertension, thus, leading to a hypothesis that metabolic disturbance may be a possible underlying common mechanism. More nuanced changes in biological processes postpartum in heart after PE are often overlooked and require comprehensive animal models to detect dysregulated metabolic pathways.

Design and method:
We used well-established transgenic rat model for PE and RNA-sequencing to create expression profiles at different time points (non-pregnant, end of pregnancy and postpartum) of preeclamptic rats and healthy controls. We performed bioinformatical analysis to identify differentially expressed genes for different groups of comparisons (physiological and pathological changes) in 4 heart regions. We used gene set enrichment analysis to identify affected biological processes with comparison to existing heart failure models. To support gene expression data and identify the most affected heart regions we also used speckle tracking echocardiography and immunostaining.

Results:
We found that all heart regions of PE animals are still affected post-partum (PEpp), while healthy controls recover after pregnancy (WTpp). Data from echocardiography and histological staining support the hypothesis of persistent cardiovascular changes after PE. Using RNAseq data, 39 genes were found to be differentially expressed in all heart regions of the heart of preeclamptic rats compared to the controls (adjusted p-value < 0.05, |logFC| > 2). Among the most disrupted pathways are fatty acid metabolism, oxidative phosphorilation and interferon-alpha/gamma responses.

Conclusions:
Our expression data supports the hypothesis that preterm metabolic aging of the heart could be the reason for increased cardiovascular risk after a preeclamptic pregnancy.
DOES ETHNICITY INFLUENCE THE RELATIONSHIP BETWEEN ALDOSTERONE AND EARLY SIGN OF CARDIAC REMODELLING? A CARDIOVASCULAR MAGNETIC RESONANCE STUDY
Authors: Faconti Luca , Mcnally Ryan , Haseler Emily , Masi Stefano , Masci Pier Giorgio , Chowienczyk Philip 
Published: May 2024

Objective:
Native T1 and T2 myocardial mapping techniques by cardiac magnetic resonance (CMR) offer quantitative assessments of myocardium composition with T1 manly related to tissue fibrosis and T2 to myocardial oedema. It has been proposed that compared to white individuals, in black subjects water retention/volume expansion driven by aldosterone could be a more prominent contributing factor to hypertension and hypertensive heart disease. Therefore, we aimed to assess differences in myocardial tissue characterization and its relation with plasma aldosterone concentration (PAC) in a dual ethnic cohort of subjects with hypertension.

Design and method:
Subjects with hypertension recruited from the outpatient service at Guys and St Thomas’ Hospital (UK) underwent a single study visit in which anthropometric measurements, blood tests and a multi-parametric CMR were performed. The latter included quantification of left ventricular mass indexed (LVMI) and native T1 and T2 relaxation times.

Results:
A dual ethnic cohort of 107 subjects (age 45±13 years (mean±SD)), 57% male were recruited. Most subjects were non-smokers (79.5%), average BMI 29.3±5.5 Kg/m2; 11% had diabetes, 23% dyslipidaemia and 2.5% a previous cardiovascular event. Black subjects (n=64) had higher PAC compared to white individuals (511±339 pmol/L vs 384.3±292 pmol/L, p=0.036) but age, BMI and blood pressure (BP) values were similar (47±14 years vs 43±12 years, 29.7±4 Kg/m2 vs 28.7±7 Kg/m2, 150±22 mmHg vs 148±23 mmHg for systolic BP respectively; all P >0.05). T1 relaxation time was similar between black and white subjects, however LVMI and T2 relaxation time were significantly higher in black subjects (66.7±24.9 g/m2 vs 55.2±10.4 g/m2 and 47.0±2.2 ms vs 45.7±2.2 ms respectively; both P<0.05). In the entire population PAC was significantly correlated with T2 mapping (Beta=0.198, P=0.025) and LVMI (Beta=0.296, P=0.016) but not T1. We also found a significant interaction between PAC, T2 mapping and ethnicity.

Conclusions:
The highest T2 relaxation time in black hypertensive likely reflects myocardial inflammation and ethnic related differences in myocardial tissue characterization could be related to PAC. Further studies are warranted to elucidate the potential pathophysiological mechanisms.
AORTIC STENOSIS AND HEART FAILURE: DIFFERENCES AND SIMILARITIES BEYOND PRESERVED EJECTION FRACTION
Authors: De Biase Nicolò , Del Punta Lavinia , Mazzola Matteo , De Carlo Marco , Mengozzi Alessandro , Nesti Lorenzo , Masi Stefano , Pugliese Nicola Riccardo 
Published: May 2024

Objective:
Degenerative aortic stenosis (AS) is highly prevalent in Western countries and shows a strong association with age and other cardiovascular risk factors such as arterial hypertension, diabetes mellitus, dyslipidaemia, and visceral obesity. The same risk factors are involved in the development of heart failure with preserved ejection fraction (HFpEF). Notwithstanding several similarities, patients with AS and preserved left ventricular ejection fraction (ASpEF) are not considered to actually have HFpEF. We sought to investigate the haemodynamic and metabolic features of patients with ASpEF both at rest and during physical effort and highlight similarities and differences with HFpEF.

Design and method:
We enrolled 148 patients with HFpEF, 150 with ASpEF (with at least moderate aortic transvalvular gradient), and 80 age- and sex-matched healthy controls. All patients received a comprehensive laboratory evaluation, a resting echocardiographic examination, and a combined cardiopulmonary-echocardiographic stress test. Patients with ASpEF who fulfilled the criteria for transcatheter aortic valve replacement (n=125) underwent cardiac computed tomography to measure aortic valve calcium score and volume.

Results:
Serum levels of N-terminal prohormone of brain natriuretic peptide were similar between HFpEF and ASpEF patients after excluding subjects with atrial fibrillation. As a marker of deregulated inflammation, epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and controls and was inversely related to peak oxygen consumption (VO2) in all subgroups (Figure). Furthermore, all patients showed a significant impairment in peak VO2 caused by a reduction in bith cardiac output (CO) and peripheral arteriovenous oxygen difference (AVO2diff). HFpEF patients displayed increased arterial stiffness, worse left ventricular-arterial coupling, and worse left atrial function. On the other hand, patients with ASpEF showed worse right ventricular-pulmonary arterial coupling. In ASpEF, disease severity, evaluated by aortic transvalvular peak velocity, mean gradient at rest and peak exercise, and aortic valve calcium score and volume, was directly related to EAT thickness.

Conclusions:
ASpEF shows substantial similarities to HFpEF. ASpEF could represent a separate phenotype in the spectrum of HFpEF; further and larger studies should investigate this hypothesis to give further insight into the pathophysiology of ASpEF.
ROLE OF CIRCULATING ENDOTHELIAL PROGENITOR CELLS AND CORRELATION WITH VASCULAR STIFFNESS AND ORGAN DAMAGE
Authors: Desantis Vanessa , Marozzi Marialuisa Sveva , Giliberti Lucia , Corvasce Francesco , Scaringella Antonella , Potenza Maria Assunta , Nacci Carmela , Montagnani Monica , Vacca Angelo , Nazzaro Pietro , Cicco Sebastiano 
Published: May 2024

Objective:
Atherosclerosis is a chronic cardiovascular disease. High plasma concentration of LDL is the main risk factor but the role of inflammation in all the stages become recently evident. Atherosclerosis and lipid metabolism change according to gender differences. Several possible markers of endothelial dysfunction and vascular stiffness have been identified, including clinical-instrumental and biochemical markers of inflammation and/or fibrosis (i.e., TNF-alpha, prostaglandin, L-Arginine/Asymmetric dimethylarginine - ADMA). A common mechanism identified in the pathogenesis of numerous CVD is endothelial dysfunction that correlates with circulating endothelial progenitor cells (EPCs). These cells are recruited from the bone marrow in response to vascular damage or tissue ischemia. In the peripheral blood, EPCs contribute to reendothelialization and neovascularization, acting as positive regulators of hemostasis and vascular integrity. A reduction in their number or function has been correlated to progression of CVD and MACE. Our project aims to assess the role of EPCs and L-ARG/ADMA in arterial stiffness and atherosclerosis.

Design and method:
Our study is a prospective experimental investigation, enrolling all patients with cardiovascular disease. Patients will undergo routine hematological and biochemical tests as well as instrumental examinations in accordance with good clinical practice. The enrolled patients will undergo a series of clinical and instrumental examinations (ABI,PWV). In in vitro experiments, EPCs will be isolated from PBMCs and functional assays will be performed. Also, Proteome Profiler Target Analytes study and ELISA assay (L-Arg/ADMA) will be performed.

Results:
There was a direct correlation between SCORE2/2-OP and PWV (r=0.70; p<0.0001). Preliminary data indicated a correlation between L-Arg/ADMA to SCORE2/2OP (r=0.36, p=0.04), Total Cholesterol (r=0.75, p=0.033) and LDL (r=0.75, p=0.031), as well as EPCs and their migration correlates to a change in folate cycle (P<0.007

Conclusions:
preliminary data suggests the importance of EPCs as specific read-out of cell activation and tissue damage in response to cardiovascular risk factors.