bluuebunny/crossref_metadata_2025 huggingface dataset:
KV4.3 PROTECTS AGAINST OXIDATIVE CAMKII ACTIVATION IN HEART FAILURE
Authors: Wang Yanggan
Published: May 2024

Objective:

Oxidative stress causes excessive CaMKII activation in heart failure which exacerbates cardiac dysfunction. We determined whether restoration of down-regulated membrane Kv4.3 expression in ventricular myocytes can block oxidative CaMKII activation in heart failure.

Design and method:

Heart failure was induced in mice by severe thoracic aortic banding. Transjugular injection of AAV-Kv4.3 was performed in mice 1 week after banding. Fluorescence spectra were measured using F-4600 spectrophotometer (Hitachi). The slit width and excitation wavelength were set to 5 mm and 270 nm, respectively. Emission spectra were increased from 280 nm to 400 nm (step = 1nm). The spectra of purified proteins were examined, including CaMKII, CaMKII and Ca2+/CaM, CaMKII and Kv4.3, CaMKII, Kv4.3, and Ca2+/CaM.

Results:

Dissociation of Kv4.3 from Kv4.3-CaMKII molecular complex or down-regulation of Kv4.3 in mouse ventricular myocytes enhanced H2O2-induced CaMKII oxidation and autophosphorylation. Only non-oxidized and unphosphorylated forms of CaMKII have been detected from the Kv4.3 immunoprecipitates in ventricular myocytes with H2O2 Incubation. Fluorescence spectra assay showed that Kv4.3 prevented the transformational change of inactive CaMKII to its active conformation in the presence of Ca2+/CaM and H2O2. In vivo transfection with AAV9-Kv4.3 had no impact on reactive oxygen species in heart failure myocardium but effectively suppressed CaMKII oxidation and activation.

Conclusions:

Kv4.3 is a potent native suppressor for oxidative CaMKII activation by binding to the regulatory domain and preventing the opening of inhibitory domain in response to Ca2+/CaM and H2O2.
NEURAL INFLAMMATION CONTRIBUTES TO VOLTAGE-GATED POTASSIUM CHANNELS DYSFUNCTION IN LUMBAR DORSAL ROOT GANGLIA IN CHRONIC HEART FAILURE RATS
Authors: Wang Hanjun
Published: May 2024

Objective:

Skeletal muscle afferent sensitization causes excessive sympatho-excitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Our recent study reported that downregulated voltage-gated potassium (Kv) channels in lumbar dorsal root ganglia (DRGs) contribute to muscle afferent sensitization in CHF rats. However, the cellular mechanisms underlying downregulated Kv channels in CHF remain unknown. We hypothesized that chronic macrophage activation contributes to Kv channels dysfunction in the lumbar DRGs in CHF.

Design and method:

Myocardial infarction (MI) was produced by left coronary artery ligation in rats. Molecular experiments were carried out to assess macrophage activation, cytokines and Kv channel expression in L4-L6 DRGs post MI. In vitro co-culture of lipopolysaccharide (LPS)-pretreated RAW264.7 (activated M1 macrophage) with 50B11 DRG neurons were performed. Patch clamp experiments were performed to assess Kv channel activity in acutely isolated muscle afferent DRG neurons. Chronic oral administration of minocycline (Mino, 20 mg/kg/day) was used to suppress macrophage activation in L4-L6 DRGs.

Results:

Compared to sham rats, male MI rats exhibited a robust increase in the number of Iba1-positive macrophages and the protein expression of Interferon regulatory factor 8 (IRF8, a pro-inflammatory macrophage marker) in L4-L6 DRGs at 8 weeks post MI, which was largely prevented by Mino (Figure 1). SEM showed macrophage infiltration into lumbar DRGs 8 weeks post MI. PCR data suggested that the mRNA expressions of pro-inflammatory cytokines including IL1beta and IL6 in lumbar DRGs were significantly elevated in male rats at 8-weeks post MI compared to sham rats. Protein expression of Kv channels including Kv1.4, 3.4, 4.2 and 4.3, was significantly downregulated in male rat L4-L6 DRGs at 8 weeks post MI. This was largely attenuated by Mino. Patch clamp data demonstrated decreased Ito current in isolated male rat muscle afferent DRG neurons 8 weeks post MI, also attenuated by Mino. Moreover, LPS-pretreated BV2 cells or RAW264.7 (LPS was washed out 4 hours after exposure, co-cultured with 50B11 DRG neurons significantly downregulated several Kv isoforms in DRG neurons.

Conclusions:

Macrophage activation contributes to Kv channels dysfunction in lumbar DRGs in CHF male rats.
CD80 AND CD86 MASKING ON ANTIGEN-PRESENTING CELLS EXHIBITED PROTECTION FROM MYOCARDIAL NECROSIS AND ISCHEMIA-REPERFUSION INJURY: A PRECLINICAL VALIDATION
Authors: Verma Vipin Kumar , Mutneja Ekta , Bhatia Jagriti , Arya D S
Published: May 2024

Objective:

Myocardial Ischemia due to coronary obstruction after a critical threshold level, resulting in myocardial damage as a consequence of myocardial cell death. However, reperfusion itself causes the generation of oxygen free radicals, disturbed cation homeostasis, and depletion of cellular energy due to the involvement of molecular signaling. Abatacept, a recombinant fusion protein that inhibits the activation of T-cells through binding with CD80 and CD86 receptors of antigen-presenting cells and prevents major inflammatory responses. This study identifies the anti-inflammatory potential of abatacept by minimizing the immune-cell activation, and infiltration at myocardium during injury.

Design and method:

This study was conducted in two parts on male Wistar rats. Firstly, abatacept was administered at 2.5, 5 & 10 mg/kg; s.c. for 21 days and evaluated in the Isoproterenol (ISO)-induced myocardial necrosis model of rats, in which ISO was injection subcutaneously on 20th and 21st day at 85 mg/kg dose, after an interval of 24 h post last ISO injection, the rat was sacrificed after hemodynamic measurement and the optimal dose of Abatacept was calculated through biochemical (oxidant-antioxidant / cardiac injury marker), histopathological and molecular investigations. Secondly, after abatacept administration at optimal dose for 21 days, the rats were anesthetized and Ischemia-Reperfusion injury was induced through LAD coronary artery ligation for 60 min and re-opening for 60 min. The effect of abatacept was based on hemodynamic, biochemical, and molecular investigation of inflammation, apoptosis, and necroptosis signaling pathway-related proteins.

Results:

Improved hemodynamics at different time intervals during ischemia and reperfusion was observed after abatacept administration. The maintained enzyme levels of anti-oxidants v/s oxidants along with cardiac injury markers correlate with the histopathology findings. The inhibition of CD28 T-cell activation abates the release of inflammatory markers and related signaling pathways proteins showing the efficacy of Abatacept. On Investigation, expression of Nrf-2, Hsp27, and Hsp 70 thereby showing efficacy of Abatacept in cardiovascular models.

Conclusions:

Abatacept was found potent drug because of its co-stimulation inhibitor activity, and hence, it inhibits inflammation, oxidation, and apoptosis in models of myocardial infarction and could be beneficial for humans after designated clinical trials.
THE ASSESSMENT OF THE IMPACT OF PHYSICAL EXERCISE LEVEL ON THE QUANTITY OF ENDOTHELIAL CELL PRECURSOR PROGENITOR CELLS IN PERIPHERAL BLOOD IN PATIENTS AFTER ACUTE CORONARY SYNDROME
Authors: Tereshchenko Nataliia , Kovalchuk Yuliia , Shumakov Valentyn , Malynovska Iryna
Published: May 2024

Objective:

To identify the correlation between the restoration of physical exercise tolerance (PET) level and the quantity of endothelial cell precursors (PCE) in peripheral blood of patients after acute coronary syndrome (ACS).

Design and method:

Ninety male patients were examined, including 79 (87.8±6.8%) with a diagnosis of myocardial infarction, of which 65 (82.3±8.4%) had STEMI and 14 (17.7±8.4%) had NSTEMI, and 11 (12±6.8%) with unstable angina. Among the comorbidities, hypertension was present in all patients (100±4.1%), diabetes mellitus in 23 (25.6±9.0%), obesity in 25 (27.8±9.3%), and overweight in 29 (32.2±9.7%). Grade II heart failure was observed in 65 patients (72.2±9.3%). The average age of the examined patients was (56.5±10.5) years. Coronary angiography revealed atherosclerotic involvement of one vessel in 23 patients (25.6±9.0%), two vessels in 26 (28.9±9.4%), and three vessels in 41 (45.6±10.3%). Hemodynamically significant three-vessel involvement was found in 24 patients (26.7±9.1%), two-vessel involvement in 31 (34.4±9.8%), and one-vessel involvement in 35 (38.9±10.1%). All patients underwent exercise testing using the graded exercise method, assessment of intracardiac hemodynamics using two-dimensional and Doppler echocardiography, coronary angiography, biochemical and general clinical blood tests, and quantification of PCE levels in peripheral blood. The results are presented as the mean value with standard deviation or frequency with a 95% confidence interval.

Results:

The obtained data indicate that there is an associative relationship between better restoration of PET levels after acute coronary syndrome and the restoration of endothelial function in patients with a favorable course of the post-infarction period during repeated examination, compared to patients whose PET levels did not exceed 50 watts (low PET). This is evidenced by a statistically significant higher number of PCE after physical exercise in the group with a favorable course and high PET (Group A) compared to the group with an unfavorable course and low PET (Group B).

Conclusions:

Studying the response in terms of changes in PCE quantity in response to physical exercise can help determine the progression of systemic endothelial dysfunction, which affects the patient's prognosis. Decreased PCE during physical exercise.
LEFT ATRIAL VOLUME, PREDICTIVE FACTOR OF THE REDUCTION OF GLS IN HYPERTENSIVE PATIENT
Authors: Bendiab Nabila Tale B , Ghalmi Abdallah , Khedim Nesrine
Published: May 2024

Objective:

Dilatation of the left atrium (LA) is usually found in high blood pressure without any valve damage. This dilatation is one of the prognostic markers and may be a reflection of left ventricular diastolic dysfunction. It can be used as one of the factors of morbi cardiovascular mortality.

Diastolic dysfunction is acknowledged to be the predominant pathophysiological mechanism in patients with heart failure with preserved ejection fraction.

Design and method:

This work consists in carrying out in a series of 200 hypertensive patients (aged 25 to 75 years) an echocardiographic study, including the LVEF, the calculation of the indexed left ventricular mass as well as the relative parietal thickness, the calculation of the volume of the left atrium and the analysis of the diastolic function and finally the study of the longitudinal deformation of the LV. Excluded from this study were patients with secondary hypertension, leaky or stenotic valve disease, arrhythmia, history of coronary insufficiency

Results:

Of the 200 hypertensive patients, 28 patients had a high LA volume, of which 27 patients had high filling pressures.

Of the 28 patients with high LA volume 18 patients (64.2%) had low GLS.

Patients with high LA volume are twice as likely to have low GLS as other patients. There is a statistically very significant relationship between lower GLS, increased left atrium volume, and increased left ventricular filling pressures in hypertensive patients. These results suggest that the increase in filling pressures is closely associated with atrioventricular interaction in patients with hypertension, with a perfect correlation with achievement of longitudinal systolic and diastolic dysfunction.

Conclusions:

The evaluation of LA size and function provides a powerful and dynamic morphophysiological marker of cardiovascular disease status that can be used longitudinally to quantify the extent of structural and functional remodeling.
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.
FIRST COMPREHENSIVE ECHOCARDIOGRAPHIC ASSESSMENT IN PATIENTS WITH VASCULAR EHLERS-DANLOS SYNDROME WITH OR WITHOUT CELIPROLOL THERAPY AT THE MAXIMUM RECOMMENDED DOSE
Authors: Buso Giacomo , Paini Anna , Agabiti-rosei Claudia , Bertacchini Fabio , Stassaldi Deborah , Capellini Sara , Aggiusti Carlo , Salvetti Massimo , De Ciuceis Carolina , Ritelli Marco , Venturini Marina , Colombi Marina , Muiesan Maria Lorenza
Published: May 2024

Objective:

Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a beta1-adrenoceptor antagonist with partial beta2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Moreover, few data on echocardiographic assessment are available in patients with vEDS.

Design and method:

Twenty patients with genetically confirmed diagnosis of vEDS followed at our Institution were divided into two groups (10 patients each) according to whether or not they were on celiprolol therapy at the maximum recommended dose (400 mg daily) for at least 12 months. Both groups were compared to 10 healthy individuals matched for sex, age, body mass index (BMI), and office blood pressure values. Each participant underwent transthoracic echocardiography with tissue Doppler analysis for a comprehensive evaluation of cardiac structure and function.

Results:

Mean age was 35 years and mean BMI was 21.6 kg/m2. Female sex was prevalent (60%). Left ventricular (LV) internal diameter values tended to be lower in patients with untreated vEDS than in healthy controls, though this difference was not statistically significant (4.33 vs 4.74 cm, respectively; p=0.053). Similar data were observed for LV mass index (56.9 vs 68.6 g/m2; p=0.093), stroke volume (56.6 vs 71.6 mL; p=0.068), and E/A ratio (1.26 vs 1.66; p=0.082), whereas an opposite trend was observed for e’ lateral (13.2 vs 12.2; p=0.096). No statistically significant difference was found between groups in terms of other parameters of LV mass, systolic and diastolic function. A normal LV geometry was found in all the cases. Indices of mechano-energetic efficiency and ventricular-arterial coupling were also similar between groups. No patient presented with aortic root dilation, mitral valve prolapse, valve insufficiency of more than mild degree, or valve stenosis of any degree.

Conclusions:

Our study suggests that patients with vEDS have normal cardiac mass and geometry, as well as normal systolic and diastolic function. Celiprolol therapy does not seem to significantly influence such aspects. Future studies on larger cohort of patients should confirm these aspects.
UNCONTROLLED HYPERTENSION AS A RISK FACTOR FOR POOR OUTCOME AFTER MYOCARDIAL INFARCTION
Authors: Bogicevic Zorana , Tasic Danijela , Ogarevic Sladjana Bozovic , Arsic Milan , Petrovic Masa , Tasic Nebojsa
Published: May 2024

Objective:

The Republic of Serbia exhibits a disproportionately high incidence of cardiovascular diseases (CVDs), particularly among the sub-45 demographic. Early-onset hypertension (HTA) is considered to be one of the most significant factors in myocardial and vascular damage, and a possible contributor for myocardial infarction (MI). This study aims to delineate the contributory role of HTA in MI onset in patients aged below 45.

Design and method:

The retrospective cohort study included 224 patients aged 45 years or younger, who were diagnosed and treated for MI at the Institute for Cardiovascular Diseases “Dedinje” from January 1, 2020, to November 1, 2023. The cohort, predominantly male (83%), had a mean age of 40.27 ± 4.65 years. For comparative analysis, patients were grouped based on the presence of early onset of HTA and subsequently compared based on MI characteristics and severity of clinical presentation. Statistical analysis was done by IBM SPSS Statistics version 23, for confidence interval <0.05.

Results:

HTA was observed in 68.3% of the cohort (mean age 40.7 ± 4.3 years), with 26.8% reporting suboptimal HTA management. Concomitant risk factors included obesity (75.9%) and smoking (67.9%). ST-segment elevation myocardial infarction (STEMI) was present in 79.9% of cases. A subset of 17 patients presented with MI in the absence of obstructive coronary artery disease. Mean ejection fraction (EF) after MI did not differ to the level of statistical significance in the HTA group versus non-HTA group, 42.68±9.7% and 44.93±10.4%, respectively (p=0.116). However, patients with poorly controlled HTA exhibited a markedly reduced EF (mean EF=39.88%, p=0.012). A low statistical correlation was observed between HTA and the number of affected coronary arteries (r = 0.106).

Conclusions:

While HTA did not significantly correlate with the severity of coronary artery disease, and was rarely an isolated CVD risk factor, its presence, particularly in uncontrolled HTA, was associated with poorer MI outcomes and myocardial damage. Further research and longitudinal patient follow-up are planned to comprehensively evaluate prognostic factors im patient with MI and uncontrolled HTA.
DECIPHERING THE NOVEL ROLE OF ERDOSTEINE IN PREVENTION OF MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN RAT
Authors: Bhardwaj Priya , Verma Vipin Kumar , Mutneja Ekta , Prajapati Vaishali , Bhatia Jagriti , Arya D S
Published: May 2024

Objective:

Myocardial ischemia-reperfusion injury (MIRI) is caused by thrombotic obstruction of the coronary artery subsequently leading to heart failure. Despite the availability of improved prognosis, MIRI is a foremost cause of morbidity and mortality worldwide. In this study, we investigated the therapeutic potential of Erdosteine (a mucoactive antioxidant molecule, with multifaceted pharmacological properties), to attenuate myocardial infarction in rat model of MIRI.

Design and method:

This study was conducted in adult male Wistar rats (n=40), randomized into five groups: Sham, IR-C (disease control), Erdosteine (80 mg/kg; s.c.) + IR, Telmisartan (10 mg/kg; orally) +IR and Erdosteine (80 mg/kg) perse groups. Erdosteine and telmisartan were administered for 28 days as a pre-treatment. On the 29th day, animals were subjected to LAD coronary artery occlusion for 1 h followed by reperfusion for 45 minutes. The cardioprotective potential was assessed through measurement of hemodynamic parameters, biochemical markers (MDA, GSH, SOD), cardiac injury markers (CK-MB and LDH), inflammatory markers (IL-6, TNF), histopathological evaluation, TUNEL assay and immunohistochemistry analysis (Bax, caspase 3, Bcl2). Further, the underlying mechanism was evaluated using immune-blotting of MAPK, Nrf-2/HO-1, and Akt/p-Akt. The statistics analysis was performed by one-way ANOVA followed by Turkey-Kramer post hoc tests.

Results:

Erdosteine and telmisartan pretreatment improves hemodynamic parameters by preserving MAP, ±LVdP/dt, and HR as compared to the IR-C group. Pretreatment markedly restored the levels of antioxidants (GSH and SOD) and decreased peroxidation marker (MDA) compared to the IR-C group. Also, the pretreatment significantly prevented the damage following IR injury as compared to the IR-C group when investigated through cardiac injury markers and histopathological evaluation. Erdosteine profoundly reversed the expressions of Bcl2/BAX ratio, in comparison to the IR-C group indicating its anti-apoptotic effect when reconfirmed through TUNEL assay. Erdosteine pretreatment preserved the levels of NF-kB, TNF, and IL-6 following IR challenge. Erdosteine pretreatment restores FABP, Nrf-2, and Hsp27.

Conclusions:

Erdosteine protects the myocardial cell membrane from peroxidation and inhibits oxidative burst and inflammation through NF-kB pathway activation. Erdosteine attenuates MIRI injury in rats preserving the MAPK and Nrf-2 signaling cascade.
NIGHTTIME BLOOD PRESSURE DIPPING PATTERNS AND MORNING SURGE IN RELATION TO DAYTIME ACTISENSITIVITY DETECTED BY AN ALL-IN-ONE MULTISENSOR BLOOD PRESSURE MONITORING DEVICE
Authors: Tomitani Naoko , Hoshide Satoshi , Kario Kazuomi
Published: May 2024

Objective:

Ambulatory blood pressure (BP) fluctuates affected by physical activity and the BP response against physical activity (actisensitivity) differs by individuals. This is the first study to investigate whether the daytime actisensitivity evaluated by a multisensor all-in-one BP monitoring device affects the nighttime BP dipping status and morning BP surge.

Design and method:

Twenty-four-hour ambulatory BP monitoring (ABPM) with simultaneously monitored physical activity was performed in the HI-JAMP study participants. Actisensitivity was calculated as the slope of the regression line between daytime systolic BP (SBP) and log-transformed physical activity over 5-min prior to corresponding each BP reading. Data from 2,692 patients (mean age 69.9 ± 11.9 years; mean body mass index 24.8 ± 4.1 kg/m2, 53.6% male) were analyzed.

Results:

Patients with hyper reactivity (upper 10 percentile of actisensitivity) had high prevalence of extreme dipper and exaggerated morning surge, while patients with negative reactivity (lower 10 percentile of actisensitivity) had higher nighttime BP and nighttime riser pattern. These results remained significant even after adjusting for 24-hr physical activity. The differences of diurnal BP variability by actisensitivity were augmented in the patients>75 years.

Conclusions:

Actisensitivity detected by a multisensor all-in-one BP monitoring device in daily life determined nighttime dipping patterns and morning surge in BP. Especially in the elderly hypertensives with actisensitivity at both extreme ends, the abnormal diurnal BP variability was augmented, suggesting a possible increased risk of cardiovascular events.
INCIDENCE OF HYPERTENSION ASSOCIATED WITH POLY-ADP-RIBOSE POLYMERASE (PARP) INHIBITORS IN COMBINATION WITH ANTIANGIOGENIC DRUGS: A META-ANALYSIS
Authors: Ma Jie , Li Caie , Wang Wenjuan , Fan Xin , Yu Jing
Published: May 2024

Objective:

poly-ADP-ribose polymerase(PARP) inhibitors have demonstrated significant anti-tumor activity in a variety of tumors, such as ovarian cancer, and some studies have found that PARP inhibitors combined with anti-angiogenic drugs have achieved significant results in the treatment of ovarian cancer compared with single drugs. While there are few studies on the vascular safety of the combination of PARP inhibitors and anti-angiogenic drugs. Therefore, We conducted a meta-analysis to assess the incidence of hypertension in patients with ovarian cancer treated with PARP inhibitors in combination with anti-angiogenic agents.

Design and method:

We reviewed PubMed, Embase, Cochrane Library and Web of Science databases to identify relevant randomised controlled trials published from inception to November 10, 2023, without language restrictions. Randomised controlled trials (RCTs) of patients with Ovarian Cancer treated with PARP inhibitors in combination with anti-angiogenic inhibitors in the experimental group, as well as available data on treatment-induced increases in blood pressure.

Results:

Five studies were selected for the final analysis, The incidence of PARP inhibitors plus anti-angiogenic agents related hypertension from 38.8% to 79.5%, compared from 0% to 59.9% in the control groups, PARP inhibitors plus anti-angiogenic agents therapies significantly increased the risk of hypertension (random-effects, OR = 10.38; P =0.04).

Conclusions:

PARP inhibitors combined with antiangiogenic inhibitors increase the risk of hypertension.
HIGH PREVALENCES OF NOCTURNAL HYPERTENSION AND ISOLATED NOCTURNAL HYPERTENSION IN LONG-STANDING VIRALLY SUPPRESSED PEOPLE LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS
Authors: Kositanurit Weerapat , Suksiriworaboot Tanawin , Nakornchai Gahn , Avihingsanon Anchalee , Chattranukulchai Pairoj
Published: May 2024

Objective:

Nocturnal hypertension (NH) and isolated nocturnal hypertension (INH) have emerged as residual risks for adverse cardiovascular events. Little is known about the prevalence among virally suppressed people living with human immunodeficiency virus (PLHIV) without a known history of hypertension (HT).

Design and method:

A cross-sectional study was conducted among virally suppressed PLHIV without a known history of HT who had normotensive office blood pressure (BP). All participants underwent 24-hour ambulatory blood pressure monitoring (ABPM). Blood pressure phenotypes were analyzed according to the 2023 ESH guidelines for the management of arterial HT. Normotension was defined as a 24-hour average BP <130/80 mmHg, NH as a nighttime BP greater than or equal to 120/70 mmHg, INH as NH but with normal both office BP (<140/90 mmHg) and daytime BP (<135/85 mmHg), and non-dipping as a drop of nighttime systolic/diastolic BP <10% compared to daytime systolic/diastolic BP.

Results:

A total of 83 participants were included with a mean age of 52.5±7.8 years (61.4% women). The mean duration of viral load suppression was 14.2±5.9 years. Overall, 67 participants (80.7%) were confirmed normotension by ABPM. The prevalences of NH and INH were 29% and 18.1%, respectively. Around half of the participants had non-dipping systolic BP (56.6%) and non-dipping diastolic BP (49.4%). Moreover, non-dipping diastolic BP was a significant predictor of NH in multivariable logistic regression analysis (OR 9.54, 95%CI 1.05-86.29; p=0.045).

Conclusions:

In this long-standing, well-suppressed PLHIV with normotensive office BP, the prevalences of NH and INH were high. Non-dipping diastolic BP might be a good predictor of NH in this population.