Pubblicazioni recenti - cardiac hypertrophy
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RyR2 Stabilizer Attenuates Cardiac Hypertrophy by Downregulating TNF-?/NF-?B/NLRP3 Signaling Pathway through Inhibiting Calcineurin.
J Cardiovasc Transl Res2024 Apr;():. doi: 10.1007/s12265-023-10376-8.
Gao Yi, Li Shuai, Liu Xueyan, Si Daoyuan, Chen Weiwei, Yang Fenghua, Sun Huan, Yang Ping,
Abstract
The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-?/NF-?B/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-?/NF-?B/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression. The present study shows for the first time that RyR2 stabilizer dantrolene attenuates cardiac hypertrophy by inhibiting the calcineurin, therefore downregulating the TNF-?/NF-?B/NLRP3 pathway.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Inhibition of miR-146b-5p alleviates isoprenaline-induced cardiac hypertrophy via regulating DFCP1.
Mol Cell Endocrinol2024 Apr;():112252. doi: 10.1016/j.mce.2024.112252.
Liu Siling, Su Linjie, Li Jie, Zhang Yuexin, Hu Xiaopei, Wang Pengcheng, Liu Peiqing, Ye Jiantao,
Abstract
Pathological cardiac hypertrophy often precedes heart failure due to various stimuli, yet effective clinical interventions remain limited. Recently, microRNAs (miRNAs) have been identified as critical regulators of cardiovascular development. In this study, we investigated the role of miR-146b-5p and its underlying mechanisms of action in cardiac hypertrophy. Isoprenaline (ISO) treatment induced significant hypertrophy and markedly enhanced the expression of miR-146b-5p in cultured neonatal rat cardiomyocytes and hearts of C57BL/6 mice. Transfection with the miR-146b-5p mimic led to cardiomyocyte hypertrophy accompanied by autophagy inhibition. Conversely, miR-146b-5p inhibition significantly alleviated ISO-induced autophagy depression, thereby mitigating cardiac hypertrophy both in vitro and in vivo. Our results showed that the autophagy-related mediator double FYVE domain-containing protein 1 (DFCP1) is a target of miR-146b-5p. MiR-146b-5p blocked autophagic flux in cardiomyocytes by suppressing DFCP1, thus contributing to hypertrophy. These findings revealed that miR-146b-5p is a potential regulator of autophagy associated with the onset of cardiac hypertrophy, suggesting a possible therapeutic strategy involving the inhibition of miR-146b-5p.
Copyright © 2024. Published by Elsevier B.V.
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Lack of cardiac remodelling in elite endurance athletes: an unexpected and not so rare finding.
Eur J Appl Physiol2024 Apr;():. doi: 10.1007/s00421-024-05489-0.
Di Gioia Giuseppe, Crispino Simone Pasquale, Maestrini Viviana, Monosilio Sara, Ortolina Davide, Segreti Andrea, Squeo Maria Rosaria, Lemme Erika, Nenna Antonio, Pelliccia Antonio,
Abstract
PURPOSE:
Endurance elite athletes are expected to present a cardiac remodelling, characterized by eccentric hypertrophy (EH), may be associated with higher sportive performances. However, not all can present a cardiac remodelling. The study aimed to identify endurance athletes without cardiac remodelling characterizing their physiologic and clinical features.
METHODS:
We studied 309 endurance athletes (cycling, rowing, canoeing, triathlon, athletics, long-distance swimming, cross-country skiing, mid-long distance track, pentathlon, biathlon, long-distance skating and Nordic-combined) examined during period of training, by clinical evaluation, ECG, echocardiogram and exercise-stress test. Sport career achievements (Olympic\World championship medals or national\world records) were recorded.
RESULTS:
EH was found in most of athletes, (n?=?126, 67% of males; n?=?85, 68.5% of females). A significant proportion,, exhibited normal geometry (NG) ( n?=?59, 31.3% in males; n?=?39, 31.4% in females). At stress test, significant differences between EH and NG athletes were found in peak power (317.1?±?71.2W in NG vs. 342.2?±?60.6W in EH, p?=?0.014 in males and 225.1?±?38.7W in NG vs. 247.1?±?37W in EH, p?=?0.003 in females), rest heart rate (66.1?±?13 in NG vs. 58.6?±?11.6 in EH, p?=?0.001 in males and 68?±?13.2 in NG vs. 59.2?±?11.2 in EH, p?=?0.001 in females) with similar ventricular extrasystoles (p?=?0.363 in males and p?=?0.492 in females). However, no significant differences in athletic achievements were registered.
CONCLUSION:
Our study demonstrates a relatively high prevalence of NG in endurance athletes, in addition to the expected EH. Athletes with NG perform worse in exercise-stress test and exhibit some less advantageous functional heart characteristics. However, the type of heart geometry is not associated with negative clinical findings.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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A Ratiometric Catalog of Protein Isoform Shifts in the Cardiac Fetal Gene Program.
bioRxiv2024 Apr;():. doi: 2024.04.09.588716.
Han Yu, Wennersten Sara A, Pandi Boomathi P, Ng Dominic C M, Lau Edward, Lam Maggie P Y,
Abstract
The fetal genetic program orchestrates cardiac development and the re-expression of fetal genes is thought to underlie cardiac disease and adaptation. Here, a proteomics ratio test using mass spectrometry is applied to find protein isoforms with statistically significant usage differences in the fetal vs. postnatal mouse heart. Changes in isoform usage ratios are pervasive at the protein level, with 104 significant events observed, including 88 paralog-derived isoform switching events and 16 splicing-derived isoform switching events between fetal and postnatal hearts. The ratiometric proteomic comparisons rediscovered hallmark fetal gene signatures including a postnatal switch from fetal ? (MYH7) toward ? (MYH6) myosin heavy chains and from slow skeletal muscle (TNNI1) toward cardiac (TNNI3) troponin I. Altered usages in metabolic proteins are prominent, including a platelet to muscle phosphofructokinase (PFKP - PFKM), enolase 1 to 3 (ENO1 - ENO3), and alternative splicing of pyruvate kinase M2 toward M1 (PKM2 - PKM1) isoforms in glycolysis. The data also revealed a parallel change in mitochondrial proteins in cardiac development, suggesting the shift toward aerobic respiration involves also a remodeling of the mitochondrial protein isoform proportion. Finally, a number of glycolytic protein isoforms revert toward their fetal forms in adult hearts under pathological cardiac hypertrophy, suggesting their functional roles in adaptive or maladaptive response, but this reversal is partial. In summary, this work presents a catalog of ratiometric protein markers of the fetal genetic program of the mouse heart, including previously unreported splice isoform markers.
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[Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy].
Zhonghua Xin Xue Guan Bing Za Zhi2024 Apr;52(4):384-390. doi: 10.3760/cma.j.cn112148-20231214-00497.
Zhang S Y, Gao S Q, Wang Z Y, Wu M, Tian Z, Zhang S Y,
Abstract
To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (=1.21, 95%: 1.01-1.44, =0.042), moderate or severe mitral regurgitation (=1.71, 95%: 1.19-2.47, =0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (=1.30, 95%: 1.10-1.54, =0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (=0.45, 95%: 0.26-0.78, =0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all >0.05). An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.
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The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure.
J Transl Med2024 Apr;22(1):375. doi: 375.
De Bartolo Anna, Pasqua Teresa, Romeo Naomi, Rago Vittoria, Perrotta Ida, Giordano Francesca, Granieri Maria Concetta, Marrone Alessandro, Mazza Rosa, Cerra Maria Carmela, Lefranc Benjamin, Leprince Jérôme, Anouar Youssef, Angelone Tommaso, Rocca Carmine,
Abstract
Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood. Here, we investigated the role of SELENOT in the pathophysiology of HF: (i) by designing a small peptide (PSELT), recapitulating SELENOT activity via the redox site, and assessed its beneficial action in a preclinical model of HF [aged spontaneously hypertensive heart failure (SHHF) rats] and against isoproterenol (ISO)-induced hypertrophy in rat ventricular H9c2 and adult human AC16 cardiomyocytes; (ii) by evaluating the SELENOT intra-cardiomyocyte production and secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, and the severe ultrastructural alterations, while counteracting key mediators of cardiac fibrosis, aging, and DNA damage and restoring desmin downregulation and SELENOT upregulation in the failing hearts. In the hemodynamic assessment, PSELT improved the contractile impairment at baseline and following ischemia/reperfusion injury, and reduced infarct size in normal and failing hearts. At cellular level, PSELT counteracted ISO-mediated hypertrophy and ultrastructural alterations through its redox motif, while mitigating ISO-triggered SELENOT intracellular production and secretion, a phenomenon that presumably reflects the extent of cell damage. Altogether, these results indicate that SELENOT could represent a novel sensor of hypertrophied cardiomyocytes and a potential PSELT-based new therapeutic approach in myocardial hypertrophy and HF.
© 2024. The Author(s).
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Incidence and prevalence of hypertension in 18-40-year-old patients referred for palpitations with normal cardiac monitor findings.
J Clin Hypertens (Greenwich)2024 Apr;():. doi: 10.1111/jch.14813.
Wasco Christopher, Khan Zeryab, Willett Aimee, Volio Andrew, Carter Cody, Kesari Aditya, Kothari Shaili, Scheidemantel Andrew, Bennett Katelyn, Schafer Jessalyn, Lockhart Marie, Chopra Nagesh,
Abstract
Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences "heart rate" and "contractility,?" the key components of "palpitation." While the prevalence of hypertension is 22.4% in 18-39-year-olds, the relationship between palpitations and hypertension remains unknown in this age group. In our study, we assessed the incidence and prevalence of hypertension over 5 years in 18-40-year-olds referred for palpitations who had no known arrhythmic cause for palpitations between January 1, 206 and December 31, 2017. We found that over a period of 2.2 (0.7-4.1) years, an additional 56% patients were diagnosed with stage 1 (65/130) and stage 2 (28/130) hypertension, increasing the prevalence from 16% at the start of the study period to 72% at the end of the study period (p
© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.
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piRNAs as emerging biomarkers and physiological regulatory molecules in cardiovascular disease.
Biochem Biophys Res Commun2024 Apr;711():149906. doi: 10.1016/j.bbrc.2024.149906.
Liu Zhihua, Zhao Xi,
Abstract
Cardiovascular diseases (CVD) represent one of the most considerable global health threats, owing to their high incidence and mortality rates. Despite the ongoing advancements in detection, prevention, treatment, and prognosis of CVD, which have resulted in a decline in both incidence and mortality rates, CVD remains a major public health concern. Therefore, novel diagnostic biomarkers and therapeutic interventions are imperative to minimise the risk of CVD. Non-coding RNAs (ncRNAs) have recently gained increasing attention, with PIWI-interacting RNAs (piRNAs) emerging as a class of small ncRNAs traditionally recognised for their role in silencing transposons within cells. Although the functional roles of PIWI proteins and piRNAs in human cells remain unclear, growing evidence suggests that these molecules are gradually becoming valuable biomarkers for the diagnosis and treatment of CVD. This review provides a comprehensive summary of the latest studies on piRNAs in CVD. This review discusses the roles of piRNAs in various cardiovascular subtypes, including myocardial hypertrophy, heart failure, myocardial infarction, and cardiac regeneration. The perceived insights may contribute novel perspectives for the diagnosis and treatment of CVD.
Copyright © 2024 Elsevier Inc. All rights reserved.
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Circular RNA circZFPM2 regulates cardiomyocyte hypertrophy and survival.
Basic Res Cardiol2024 Apr;():. doi: 10.1007/s00395-024-01048-y.
Neufeldt Dimyana, Schmidt Arne, Mohr Elisa, Lu Dongchao, Chatterjee Shambhabi, Fuchs Maximilian, Xiao Ke, Pan Wen, Cushman Sarah, Jahn Christopher, Juchem Malte, Hunkler Hannah Jill, Cipriano Giuseppe, Jürgens Bjarne, Schmidt Kevin, Groß Sonja, Jung Mira, Hoepfner Jeannine, Weber Natalie, Foo Roger, Pich Andreas, Zweigerdt Robert, Kraft Theresia, Thum Thomas, Bär Christian,
Abstract
Hypertrophic cardiomyopathy (HCM) constitutes the most common genetic cardiac disorder. However, current pharmacotherapeutics are mainly symptomatic and only partially address underlying molecular mechanisms. Circular RNAs (circRNAs) are a recently discovered class of non-coding RNAs and emerged as specific and powerful regulators of cellular functions. By performing global circRNA-specific next generation sequencing in cardiac tissue of patients with hypertrophic cardiomyopathy compared to healthy donors, we identified circZFPM2 (hsa_circ_0003380). CircZFPM2, which derives from the ZFPM2 gene locus, is a highly conserved regulatory circRNA that is strongly induced in HCM tissue. In vitro loss-of-function experiments were performed in neonatal rat cardiomyocytes, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and HCM-patient-derived hiPSC-CMs. A knockdown of circZFPM2 was found to induce cardiomyocyte hypertrophy and compromise mitochondrial respiration, leading to an increased production of reactive oxygen species and apoptosis. In contrast, delivery of recombinant circZFPM2, packaged in lipid-nanoparticles or using AAV-based overexpression, rescued cardiomyocyte hypertrophic gene expression and promoted cell survival. Additionally, HCM-derived cardiac organoids exhibited improved contractility upon CM-specific overexpression of circZFPM2. Multi-Omics analysis further promoted our hypothesis, showing beneficial effects of circZFPM2 on cardiac contractility and mitochondrial function. Collectively, our data highlight that circZFPM2 serves as a promising target for the treatment of cardiac hypertrophy including HCM.
© 2024. The Author(s).
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Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits.
Curr Med Sci2024 Apr;44(2):450-461. doi: 10.1007/s11596-024-2851-9.
Ding Xiao-Yun, Zhang Hao, Qiu Yu-Mei, Xie Meng-Die, Wang Hu, Xiong Zheng-Yu, Li Ting-Ting, He Chun-Ni, Dong Wei, Tang Xi-Lan,
Abstract
OBJECTIVE:
Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy.
METHODS:
The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism.
RESULTS:
Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1?, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1?. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression.
CONCLUSION:
CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.
© 2024. Huazhong University of Science and Technology.
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Postdevelopment Performance and Validation of the Artificial Intelligence-Enhanced Electrocardiogram for Detection of Cardiac Amyloidosis.
JACC Adv2023 Oct;2(8):. doi: 100612.
Harmon David M, Mangold Kathryn, Suarez Abraham Baez, Scott Christopher G, Murphree Dennis H, Malik Awais, Attia Zachi I, Lopez-Jimenez Francisco, Friedman Paul A, Dispenzieri Angela, Grogan Martha,
Abstract
BACKGROUND:
We have previously applied artificial intelligence (AI) to an electrocardiogram (ECG) to detect cardiac amyloidosis (CA).
OBJECTIVES:
In this validation study, the authors observe the postdevelopment performance of the AI-enhanced ECG to detect CA with respect to multiple potential confounders.
METHODS:
Amyloid patients diagnosed after algorithm development (June 2019-January 2022) with a 12-lead ECG were identified (n = 440) and were required to have CA. A 15:1 age- and sex-matched control group was identified (n = 6,600). Area under the receiver operating characteristic (AUC) was determined for the cohort and subgroups.
RESULTS:
The average age was 70.4 ± 10.3 years, 25.0% were female, and most patients were White (91.3%). In this validation, the AI-ECG for amyloidosis had an AUC of 0.84 (95% CI: 0.82-0.86) for the overall cohort and between amyloid subtypes, which is a slight decrease from the original study (AUC 0.91). White, Black, and patients of "other" races had similar algorithm performance (AUC >0.81) with a decreased performance for Hispanic patients (AUC 0.66). Algorithm performance shift over time was not observed. Low ECG voltage and infarct pattern exhibited high AUC (>0.90), while left ventricular hypertrophy and left bundle branch block demonstrated lesser performance (AUC 0.75 and 0.76, respectively).
CONCLUSIONS:
The AI-ECG for the detection of CA maintained an overall strong performance with respect to patient age, sex, race, and amyloid subtype. Lower performance was noted in left bundle branch block, left ventricular hypertrophy, and ethnically diverse populations emphasizing the need for subgroup-specific validation efforts.
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Characteristics of heart failure with a preserved ejection fraction in black South African patients.
Int J Cardiol Heart Vasc2024 Jun;52():101408. doi: 101408.
van Hoogland-van Heerden M, Böhmer L H, Heyneke O, Lechaba T, Scott L, Norton G, Woodiwiss A, Mntla P, Majane Ohi,
Abstract
BACKGROUND:
Heart failure with a preserved ejection fraction (HFpEF) is common in the elderly (?75 years) and associated with arterial stiffness. The mean age of HFpEF presentation is lower (40-55 years) in sub-Saharan Africa. No clinical study has been conducted on HFpEF in identifying and characterising this phenotype at a younger age, moreover in a South African black population where the risk of HFpEF is two times higher than in other ethnic groups. This study investigated the characteristics of HFpEF in a black South African population, the biochemical markers that predict HFpEF and cardiac structural changes in this HF phenotype.
METHODS:
Sixty-six participants with HFpEF and 213 controls were enrolled. All participants gave informed consent and completed a standardised questionnaire. Echocardiographic, anthropometric, central haemodynamic measurements, pulse wave velocity (PWV) and biomarker analysis were done.
RESULTS:
The mean age of HFpEF participants was 54.88 ± 13.51 years. Most of the participants (76 %) were between 20 and 64 years, while only 24 % were older. HFpEF participants were hypertensive, and more obese with increased incidence of alcohol consumption. PWV was increased in HFpEF (9.97 ± 2.78 m/s) when compared to participants without HFpEF (6.11 ± 2.18 m/s), p
CONCLUSION:
HFpEF in South Africa is predominant in obese young to middle-age individuals with arterial stiffness and who consume alcohol regularly. NT-proBNP could be used to diagnose HFpEF, however, should be interpreted with caution in populations with a high prevalence of obesity.
© 2024 The Authors. Published by Elsevier B.V.
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Tri-ponderal mass index and left ventricular hypertrophy in a cohort of caucasian children and adolescents with obesity.
Ital J Pediatr2024 Apr;50(1):75. doi: 75.
Vizzuso Sara, Torto Alberico Del, Fiore Giulia, Carugo Stefano, Zuccotti Gianvincenzo, Verduci Elvira,
Abstract
BACKGROUND:
Pediatric obesity is a global emerging burden for society; among its health-related consequences there are hypertension (HTN) and left ventricular hypertrophy (LVH). Several anthropometric indices have been investigated for the early identification of cardiovascular risk in children. The aim of the present study was to assess whether tri-ponderal mass index (TMI) was associated with LVH in a cohort of Caucasian children and adolescents with obesity.
METHODS:
In this observational study, 63 children and adolescents with obesity aged 7-to-16 years were enrolled. During outpatient visits, adiposity, and cardio-metabolic indices (BMI z-score, WHR, TMI, ABSI) were collected. All subjects underwent a 24-hour ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography.
RESULTS:
Children and adolescents with obesity with LVH had significantly higher BMI z-score (p?=?0.009), WHR (p?=?0.006) and TMI (p?=?0.026) compared to children without LVH. WC and WHR were the only indices significantly associated with left ventricular mass index (LVMI).
CONCLUSION:
Left ventricular remodeling is associated with the cardio-metabolic risk markers WC and WHR, but not with the adiposity index TMI among children with obesity.
© 2024. The Author(s).
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Associated factors with the occurrence of in-hospital cardiac arrest in patients admitted to internal medicine wards for non-cardiovascular causes.
Med Clin (Barc)2024 Apr;():. doi: S0025-7753(24)00131-3.
Carmona-Puerta Raimundo, Choque-Laura José Luis, Chávez-González Elibet, Peñaló-Batista Joel, Martínez-Sánchez Marielys Del Carmen, Lorenzo-Martínez Elizabeth,
Abstract
BACKGROUND AND OBJECTIVE:
In-hospital cardiac arrest (IHCA) has a low survival rate, so it is essential to recognize the cases with the highest probability of developing it. The aim of this study is to identify factors associated with the occurrence of IHCA.
MATERIAL AND METHODS:
A single-center case-control study was conducted including 65 patients admitted to internal medicine wards for non-cardiovascular causes who experienced IHCA, matched with 210 admitted controls who did not present with IHCA.
RESULTS:
The main reason for admission was pneumonia. The most prevalent comorbidity was arterial hypertension. Four characteristics were strongly and independently associated with IHCA presentation, these are electrical left ventricular hypertrophy (LVH) (OR: 13.8; 95% IC: 4.7-40.7), atrial fibrillation (OR: 9.4: 95% CI: 4.3-20.6), the use of drugs with known risk of torsades de pointes (OR: 2.7; 95% CI: 1.3-5.5) and the combination of the categories known risk plus conditional risk (OR: 17.1; 95% CI: 6.7-50.1). The first two detected in the electrocardiogram taken at the time of admission.
CONCLUSION:
In admitted patients for non-cardiovascular causes, the use of drugs with a known risk of torsades de pointes, as well as the detection of electrical LVH and atrial fibrillation in the initial electrocardiogram, is independently associated with a higher probability of suffering a IHCA.
Copyright © 2024 Elsevier España, S.L.U. All rights reserved.
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Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation.
Heart Rhythm2024 Apr;():. doi: S1547-5271(24)02389-0.
Fu Hui, Kong Bin, Shuai Wei, Zhu Jun, Wang Xi, Tang Yanhong, Huang He, Huang Congxin,
Abstract
BACKGROUND:
Heart failure (HF) is usually accompanied by the activation of the sympathetic nerve, and the excessive activation of the sympathetic nerve also promotes cardiac remodeling and cardiac dysfunction. In the isoproterenol (ISO) induced animal model, it is often accompanied by myocardial hypertrophy, fibrosis, and inflammation. Leukocyte immunoglobulin-like receptor B4a (Lilrb4a) is an immunosuppressive regulatory receptor and plays a vital role in cardiovascular disease. However, the effect of Lilrb4a on ventricular arrhythmias from ISO-induced mice model remains unclear.
OBJECTIVE:
The purpose of this study was to explore the role and molecular mechanism of Lilrb4a in ISO-induced arrhythmogenic remodeling.
METHODS:
Lilrb4a knockout mice and Lilrb4a overexpression mice were infused with ISO (15?mg/kg/24h, 4 weeks). Echocardiography and Histology were used to evaluate myocardial hypertrophy and cardiac structural remodeling. Surface ECG and Electrophysiological examination were used to evaluate cardiac electrical remodeling and the susceptibility to ventricular arrhythmias (VAs). qRT-PCR and Western Blotting were used to detect the expression levels of ion channel proteins and signal pathway proteins.
RESULTS:
The results discovered that ISO induced cardiac hypertrophy, fibrosis, and inflammation, and led to electrical remodeling and the occurrence of VAs. Lilrb4a alleviated cardiac structural and electrical remodeling and protected against the occurrence of VAs in ISO-induced mice by gain- or loss-of-function approaches. The mechanism is that Lilrb4a inhibited NF-kB signaling and p38 signaling activation medicated by TAK1.
CONCLUSIONS:
Lilrb4a alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation through the regulation of NF-kB signaling and p38 signaling activation.
Copyright © 2024. Published by Elsevier Inc.
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Influence of age and sex on physical, cardiac electrical and functional alterations in progressive hyperoxia treatment: A time course study in a murine model.
Exp Gerontol2024 Apr;191():112435. doi: 10.1016/j.exger.2024.112435.
Ayalasomayajula Yashwant, Hesaraghatta Anagha, Dantuluri Neha, Yassine Jenna, Saleem Faizan, Mansour Hussein, Chayawatto Chayapatou, Rangarajan Nishank, Rangarajan Sashank, Krishnan Smrithi, Panguluri Siva Kumar,
Abstract
Oxygen supplementation is a widely used treatment for ICU patients. However, it can lead to hyperoxia, which in turn can result in oxidative stress, cardiac remodeling, and even mortality. This paper expands upon previous research conducted by our lab to establish time-dependent cardiac changes under hyperoxia. In this study, both young and aged mice (male and female) underwent 72 h of hyperoxia exposure and were monitored at 24-hour intervals for cardiac electrophysiological and functional parameters using ECG and electrocardiogram data. Our analysis showed that young male mice experienced significant weight loss as well as significant lung edema by 48 h. Although young male mice were highly susceptible to physical changes, they were resistant to early cardiac functional and electrophysiological changes compared to the other groups. Both young and aged female and aged males developed functional impairments by 24 h of hyperoxia exposure. Furthermore, sex and age differences were noted in the onset of electrophysiological changes. While some groups could resist early cardiac remodeling, our data suggests that 72 h of hyperoxia exposure is sufficient to induce significant cardiac remodeling across all age and sex groups. Our data establishes that time-dependent cardiac changes due to oxygen supplementation can have devastating consequences even with short exposure periods. These findings can aid in developing clinical practices for individuals admitted to the ICU by elucidating the impact of aging, sex, and length of stay under mechanical ventilation to limit hyperoxia-induced cardiac remodeling.
Published by Elsevier Inc.
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Intramyocardial calcification in apical hypertrophic cardiomyopathy assessed using multimodality imaging: a case series.
ESC Heart Fail2024 Apr;():. doi: 10.1002/ehf2.14775.
Radano Ilaria, Mabritto Barbara, Luceri Stefania, Bongioanni Sergio, Maiellaro Francesco, Zappia Luca, Lario Chiara, Macera Annalisa, Cirillo Stefano, Pizzuti Alfredo, Citro Rodolfo, Galasso Gennaro, Musumeci Giuseppe,
Abstract
Apical hypertrophic cardiomyopathy (ApHCM) is an HCM variant, affecting frequently males in midlife. It is characterized by apical obliteration and persistent diastolic contraction, often resulting in microvascular ischaemia. We report five cases of ApHCM, with evidence of intramyocardial calcification on echocardiogram. On cardiac magnetic imaging (MRI), a hypointense component at early gadolinium enhancement (EGE) sequences, compatible with calcium, and a deep layer, with hyperintensity at late gadolinium enhancement (LGE) sequences, referable to fibrosis, suggest an endomyocardial fibrosis (EMF) diagnosis. EMF pathologic hallmark is endocardium and myocardium scarring, evolving to dystrophic calcification. It is found only in few ApHCM patients. Our series is the largest one described until now. Analysing patients' history, coexistent inflammatory triggers were evident in all of them, so their co-morbidities could represent a further cause of small vessel disease, in the context of ischaemic microvascular stress due to hypertrophy, leading to fibrosis and dystrophic calcification. This series could demonstrate the relation between apical fibrosis/calcification and microvascular ischaemia due to hypertrophy and inflammatory triggers.
© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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PM-induced iron homeostasis imbalance triggers cardiac hypertrophy through ferroptosis in a selective autophagy crosstalk manner.
Redox Biol2024 Apr;72():103158. doi: 103158.
Li Tianyu, Sun Mengqi, Sun Qinglin, Ren Xiaoke, Xu Qing, Sun Zhiwei, Duan Junchao,
Abstract
Exposure to PM is correlated with cardiac remodeling, of which cardiac hypertrophy is one of the main clinical manifestations. Ferroptosis plays an important role in cardiac hypertrophy. However, the potential mechanism of PM-induced cardiac hypertrophy through ferroptosis remains unclear. This study aimed to explore the molecular mechanism of cardiac hypertrophy caused by PM and the intervention role of MitoQ involved in this process. The results showed that PM could induce cardiac hypertrophy and dysfunction in mice. Meanwhile, the characteristics of ferroptosis were observed, such as iron homeostasis imbalance, lipid peroxidation, mitochondrial damage and abnormal expression of key molecules. MitoQ treatment could effectively mitigate these alternations. After treating human cardiomyocyte AC16 with PM, ferroptosis activator (Erastin) and inhibitor (Fer-1), it was found that PM could promote ferritinophagy and lead to lipid peroxidation, mitochondrial dysfunction as well as the accumulation of intracellular and mitochondrial labile iron. Subsequently, mitophagy was activated and provided an additional source of labile iron, enhancing the sensitivity of AC16 cells to ferroptosis. Furthermore, Fer-1 alleviated PM-induced cytotoxicity and iron overload in the cytoplasm and mitochondria of AC16 cells. It was worth noting that during the process of PM caused ferroptosis, abnormal iron metabolism mediated the activation of ferritinophagy and mitophagy in a temporal order. In addition, NCOA4 knockdown reversed the iron homeostasis imbalance and lipid peroxidation caused by PM, thereby alleviating ferroptosis. In summary, our study found that iron homeostasis imbalance-mediated the crosstalk of ferritinophagy and mitophagy played an important role in PM-induced ferroptosis and cardiac hypertrophy.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
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NASH triggers cardiometabolic HFpEF in aging mice.
Geroscience2024 Apr;():. doi: 10.1007/s11357-024-01153-9.
Kucsera Dániel, Ruppert Mihály, Sayour Nabil V, Tóth Viktória E, Kovács Tamás, Heged?s Zsombor I, Onódi Zsófia, Fábián Alexandra, Kovács Attila, Radovits Tamás, Merkely Béla, Pacher Pál, Ferdinandy Péter, Varga Zoltán V,
Abstract
Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68 macrophage count with increased Il1b expression. Conventional echocardiography failed to reveal subtle change in myocardial function; however, 2D speckle tracking echocardiography was able to identify diastolic deterioration. NASH had greater impact on aged animals resulting in cardiac hypertrophy, fibrosis, and inflammation.
© 2024. The Author(s).
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Calorie restriction anti-hypertrophic effects are associated with improved mitochondrial content, blockage of Ca-induced mitochondrial damage, and lower reverse electron transport-mediated oxidative stress.
Free Radic Res2024 Apr;():1-18. doi: 10.1080/10715762.2024.2342962.
Brito Lucas Aline Maria, Bezerra Palacio Plinio, Oliveira Cunha Pedro Lourenzo, Tarso Facundo Heberty,
Abstract
Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy. Our findings suggest that calorie restriction inhibits cardiac pathological growth while also lowering mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Calorie restriction also attenuated the opening of the Ca-induced mitochondrial permeability transition pore. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutatione peroxidase activity) and HW/TL, leading to the maintenance of protein sulphydryls and glutathione levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether calorie restriction could alter cardiac beta-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie restricted hearts have preserved beta-adrenergic signaling. In contrast, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to beta-adrenergic activation using isoproterenol (50?nM). Despite protecting against cardiac hypertrophy, calorie restriction did not alter the lack of responsiveness to isoproterenol in isolated hearts harvested from isoproterenol-treated rats. These results suggest (through a series of mitochondrial, oxidative stress, and cardiac hemodynamic studies) that calorie restriction possesses beneficial effects against hypertrophic cardiomyopathy.
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