SOSTIENICI
Pubblicazioni recenti - cardiac hypertrophy
-
Differential diagnosis of common etiologies of left ventricular hypertrophy using a hybrid CNN-LSTM model.
Sci Rep2022 Dec;12(1):20998. doi: 10.1038/s41598-022-25467-w.
Hwang In-Chang, Choi Dongjun, Choi You-Jung, Ju Lia, Kim Myeongju, Hong Ji-Eun, Lee Hyun-Jung, Yoon Yeonyee E, Park Jun-Bean, Lee Seung-Pyo, Kim Hyung-Kwan, Kim Yong-Jin, Cho Goo-Yeong,
Abstract
Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n?=?620), validation (n?=?155), and test sets (n?=?155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.
© 2022. The Author(s).
Guarda su PubMed
-
GSK126 an Inhibitor of Epigenetic Regulator EZH2 Suppresses Cardiac Fibrosis by Regulating EZH2-PAX6-CXCL10 Pathway.
Biochem Cell Biol2022 Dec;():. doi: 10.1139/bcb-2022-0224.
Aziz Shireen, Yalan Li, Raza Muhammad Ahmer, Lemin Jiao, Akram Hafiz Muhammad Bilal, Zhao Wen,
Abstract
Myocardial fibrosis is a common pathological companion of various cardiovascular diseases. To date, the role of enhancer of zeste homolog 2 (EZH2) in cancer has been well demonstrated including in renal carcinoma and its inhibitors have entered the stage of phase I/II clinical trials. However, the precise mechanism of EZH2 in cardiac diseases is largely unclear. In the current study, we first found that EZH2 expression was increased in Ang-II treated cardiac fibroblasts (CFs) and mouse heart homogenates following isoproterenol (ISO) administration for 21 days, respectively. Ang-II induces CFs activation and increased collagen-I, collagen-III, ?-SMA, EZH2, and trimethylates lysine 27 on histone 3 (H3K27me3) expressions can be reversed by EZH2 inhibitor (GSK126) and EZH2 siRNA. The ISO induced-cardiac hypertrophy, and fibrosis in vivo which were also related to the upregulation of EZH2 and its downstream target, H3K27me3, could be recovered by GSK126. Furthermore, the upregulation of EZH2 induces the decrease of paired box 6 (PAX6) and C-X-C motif ligand 10 (CXCL10) "which" was also reversed by GSK126 treatment. In summary, the present evidence strongly suggests that GSK126 could be a therapeutic intervention blunting the development and progression of myocardial fibrosis in an EZH2-PAX6-CXCL10-dependent manner.
Guarda su PubMed
-
Activation of Phosphodiesterase 3A: New Hope for Cardioprotection.
Circulation2022 Dec;146(23):1779-1782. doi: 10.1161/CIRCULATIONAHA.122.062215.
Chiong Mario, Houslay Miles D, Lavandero Sergio,
Guarda su PubMed
-
Coefficient of R-R interval variations under deep breathing load in patients with wild-type transthyretin amyloid cardiomyopathy: A case-control study.
Health Sci Rep2023 Jan;6(1):e938. doi: e938.
Nagayoshi Yasuhiro, Kawano Hiroaki, Nishihara Taiki, Morikawa Kei, Nagano Haruka, Hanatani Shinsuke, Sakaino Naritsugu, Tsujita Kenichi,
Abstract
BACKGROUND AND AIMS:
An autonomic nervous disorder is an important characteristic of cardiac amyloidosis; however, the prevalence of autonomic dysfunction in wild-type transthyretin amyloidosis (ATTR) has not been established. Analysis of the R-R interval coefficient of variation (CVR-R) is a noninvasive method to measure parasympathetic activity. We aimed to assess autonomic dysfunction of ATTR and determine the utility of CVR-R for the detection of ATTR in other cardiac diseases.
METHODS:
This is a single-center, retrospective, case-control study. Fifty patients with heart failure (HF) were studied. The etiologies of HF were as follows: ATTR, ?=?10; previous myocardial infarction (MI), ?=?20; and left ventricular hypertrophy (LVH) due to other disease processes (e.g., aortic stenosis), ?=?20. We measured the CVR-R at rest (CVR-R), CVR-R with deep breaths (CVR-R), and the change rate (CVR-R. The relative change formula is as follows: CVR-R?=?(CVR-R?-?CVR-R)/CVR-R ?100 (%).
RESULTS:
There was no difference in the CVR-R levels among the three groups. The CVR-R levels in the ATTR group were significantly lower (ATTR: -8.77 [-43.8 to 10.9]; LVH: 67.4 [38.7 to 89.4]; MI: 83.7 [60.4 to 142.9]). Based on the receiver operative characteristic curve analysis to identify ATTR in HF, the best cut-off value for the CVR-R was 19.7 (area under the curve: 0.848).
CONCLUSION:
Our data suggested autonomic dysfunction in patients with ATTR. Measurement of the CVR-R in HF patients may be a convenient support tool for the detection of ATTR.
© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.
Guarda su PubMed
-
Blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding macrophage infiltration.
Front Pharmacol2022 ;13():1058268. doi: 1058268.
Qiu Ze-Yang, Yu Wei-Jia, Bai Jie, Lin Qiu-Yue,
Abstract
Cardiac remodeling is an important mechanism of heart failure, which frequently results from leukocyte infiltration. Vascular cellular adhesion molecule-1 (VCAM-1) plays a critical role in leukocyte adhesion and transmigration. However, the importance of VCAM-1 in the development of angiotensin II (Ang II)-induced cardiac remodeling remains unclear. Wild-type (WT) mice were infused with Ang II (1,000 ng/kg/min) for 14 days and simultaneously treated with VCAM-1 neutralizing antibody (0.1 or 0.2 mg) or IgG control. Systolic blood pressure (SBP) and cardiac function were detected by a tail-cuff and echocardiography. Cardiac remodeling was evaluated by histological staining. Adhesion and migration of bone marrow macrophages (BMMs) were evaluated . Our results indicated that VCAM-1 levels were increased in the serum of patients with heart failure (HF) and the hearts of Ang II-infused mice. Furthermore, Ang II-caused hypertension, cardiac dysfunction, hypertrophy, fibrosis, infiltration of VLA-4+ BMMs and oxidative stress were dose-dependently attenuated in mice administered VCAM-1 neutralizing antibody. In addition, blocking VCAM-1 markedly alleviated Ang II-induced BMMs adhesion and migration, therefore inhibited cardiomyocyte hypertrophy and fibroblast activation. In conclusion, the data reveal that blocking VCAM-1 ameliorates hypertensive cardiac remodeling by impeding VLA-4+ macrophage infiltration. Selective blockage of VCAM-1 may be a novel therapeutic strategy for hypertensive cardiac diseases.
Copyright © 2022 Qiu, Yu, Bai and Lin.
Guarda su PubMed
-
PulDi-COVID: Chronic Obstructive Pulmonary (Lung) Diseases With COVID-19 Classification Using Ensemble Deep Convolutional Neural Network From Chest X-Ray Images To Minimize Severity And Mortality Rates.
Biomed Signal Process Control2022 Nov;():104445. doi: 104445.
Bhosale Yogesh H, Sridhar Patnaik K,
Abstract
BACKGROUND:
and ObjectivIn the current COVID-19 outbreak, efficient testing of COVID-19 individuals has proven vital to limiting and arresting the disease's accelerated spread globally. It has been observed that the severity and mortality ratio of COVID-19 affected patients is at greater risk because of chronic pulmonary diseases. This study looks at radiographic examinations exploiting chest X-ray images (CXI), which have become one of the utmost feasible assessment approaches for pulmonary disorders, including COVID-19. Deep Learning(DL) remains an excellent image classification method and framework; research has been conducted to predict pulmonary diseases with COVID-19 instances by developing DL classifiers with nine class CXI. However, a few claim to have strong prediction results; because of noisy and small data, their recommended DL strategies may suffer from significant deviation and generality failures.
METHODS:
Therefore, a unique CNN model(PulDi-COVID) for detecting nine diseases (atelectasis, bacterial-pneumonia, cardiomegaly, covid19, effusion, infiltration, no-finding, pneumothorax, viral-Pneumonia) using CXI has been proposed using the SSE algorithm. Several tranfer-learning models: VGG16, ResNet50, VGG19, DenseNet201, MobileNetV2, NASNetMobile, ResNet152V2, DenseNet169 are trained on CXI of chronic lung diseases and COVID-19 instances. Given that the proposed thirteen SSE ensemble models solved DL's constraints by making predictions with different classifiers rather than a single, we present PulDi-COVID, an ensemble DL model that combines DL with ensemble learning. The PulDi-COVID framework is created by incorporating various snapshots of DL models, which have spearheaded chronic lung diseases with COVID-19 cases identification process with a deep neural network produced CXI by applying a suggested SSE method. That is familiar with the idea of various DL perceptions on different classes.
RESULTS:
PulDi-COVID findings were compared to thirteen existing studies for nine-class classification using COVID-19. Test results reveal that PulDi-COVID offers impressive outcomes for chronic diseases with COVID-19 identification with a 99.70% accuracy, 98.68% precision, 98.67% recall, 98.67% F1 score, lowest 12 CXIs zero-one loss, 99.24% AUC-ROC score, and lowest 1.33% error rate. Overall test results are superior to the existing Convolutional Neural Network(CNN). To the best of our knowledge, the observed results for nine-class classification are significantly superior to the state-of-the-art approaches employed for COVID-19 detection. Furthermore, the CXI that we used to assess our algorithm is one of the larger datasets for COVID detection with pulmonary diseases.
CONCLUSION:
The empirical findings of our suggested approach PulDi-COVID show that it outperforms previously developed methods. The suggested SSE method with PulDi-COVID can effectively fulfill the COVID-19 speedy detection needs with different lung diseases for physicians to minimize patient severity and mortality.
© 2022 Elsevier Ltd. All rights reserved.
Guarda su PubMed
-
SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases.
Aging Dis2022 Dec;13(6):1787-1822. doi: 10.14336/AD.2022.0413.
Guo Zhenyang, Li Peng, Ge Junbo, Li Hua,
Abstract
As an important NAD-dependent enzyme, SIRT6 has received significant attention since its discovery. In view of observations that SIRT6-deficient animals exhibit genomic instability and metabolic disorders and undergo early death, SIRT6 has long been considered a protein of longevity. Recently, growing evidence has demonstrated that SIRT6 functions as a deacetylase, mono-ADP-ribosyltransferase and long fatty deacylase and participates in a variety of cellular signaling pathways from DNA damage repair in the early stage to disease progression. In this review, we elaborate on the specific substrates and molecular mechanisms of SIRT6 in various physiological and pathological processes in detail, emphasizing its links to aging (genomic damage, telomere integrity, DNA repair), metabolism (glycolysis, gluconeogenesis, insulin secretion and lipid synthesis, lipolysis, thermogenesis), inflammation and cardiovascular diseases (atherosclerosis, cardiac hypertrophy, heart failure, ischemia-reperfusion injury). In addition, the most recent advances regarding SIRT6 modulators (agonists and inhibitors) as potential therapeutic agents for SIRT6-mediated diseases are reviewed.
copyright: © 2022 Guo et al.
Guarda su PubMed
-
Membrane Estrogen Receptor Beta is Sufficient to Mitigate Cardiac Cell Pathology.
Endocrinology2022 Dec;():. doi: bqac200.
Ahluwalia Amrita, Hoa Neil, Moreira Debbie, Aziz Daniel, Singh Karanvir, Patel Khushin N, Levin Ellis R,
Abstract
Estrogen acting through estrogen receptor beta has been shown to oppose the stimulation of cardiac myocytes and cardiac fibroblasts that results in cardiac hypertrophy and fibrosis. Previous work has implicated signal transduction from ER? as being important to the function of estrogen in these regards. Here we address whether membrane ER? is sufficient to oppose key mechanisms by which Angiotensin II stimulates cardiac cell pathology. To do this we first defined essential structural elements within ER? that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ER? that is required and sufficient for cell membrane localization in mice and is the same site in humans. Here we determined in CHO cells, and mouse and rat myocytes and cardiac fibroblasts, the impact on multiple aspects of signal transduction by expressing wild type or a C418A mutant ER?. To test the importance of the nuclear receptor, we determined a four amino acid deletion in the E domain of ER? that strongly blocked nuclear localization. Using these tools, we expressed wild type and mutant ER? constructs into cardiomyocytes and cardiac fibroblasts from ER? deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by Angiotensin II and whether the membrane ER? is necessary and sufficient.
Published by Oxford University Press on behalf of the Endocrine Society 2022.
Guarda su PubMed
-
The loss of cardiac SIRT3 decreases metabolic flexibility and proteostasis in an age-dependent manner.
Geroscience2022 Dec;():. doi: 10.1007/s11357-022-00695-0.
Li Ping, Newhardt Maria F, Matsuzaki Satoshi, Eyster Craig, Pranay Atul, Peelor Frederick F, Batushansky Albert, Kinter Caroline, Subramani Kumar, Subrahmanian Sandeep, Ahamed Jasimuddin, Yu Pengchun, Kinter Michael, Miller Benjamin F, Humphries Kenneth M,
Abstract
SIRT3 is a longevity factor that acts as the primary deacetylase in mitochondria. Although ubiquitously expressed, previous global SIRT3 knockout studies have shown primarily a cardiac-specific phenotype. Here, we sought to determine how specifically knocking out SIRT3 in cardiomyocytes (SIRTcKO mice) temporally affects cardiac function and metabolism. Mice displayed an age-dependent increase in cardiac pathology, with 10-month-old mice exhibiting significant loss of systolic function, hypertrophy, and fibrosis. While mitochondrial function was maintained at 10 months, proteomics and metabolic phenotyping indicated SIRT3 hearts had increased reliance on glucose as an energy substrate. Additionally, there was a significant increase in branched-chain amino acids in SIRT3cKO hearts without concurrent increases in mTOR activity. Heavy water labeling experiments demonstrated that, by 3 months of age, there was an increase in protein synthesis that promoted hypertrophic growth with a potential loss of proteostasis in SIRT3cKO hearts. Cumulatively, these data show that the cardiomyocyte-specific loss of SIRT3 results in severe pathology with an accelerated aging phenotype.
© 2022. The Author(s).
Guarda su PubMed
-
Tissue Inhibitor of Metalloproteinase 4 (Timp4) Deletion in Mice Impacts Maternal Cardiac Function during Pregnancy and Postpartum.
Am J Physiol Heart Circ Physiol2022 Dec;():. doi: 10.1152/ajpheart.00408.2022.
Thurstin Ashley A, Egeli Allison N, Goldsmith Edie C, Spinale Francis G, LaVoie Holly A,
Abstract
Reversible physiological cardiac hypertrophy of the maternal heart occurs during pregnancy and involves extracellular matrix (ECM) remodeling. Previous mouse studies revealed that changes in ECM molecules accompany functional changes in the left ventricle (LV) during late pregnancy and postpartum. In this study, we aimed to determine the effect of global Timp4 deletion in female mice on LV functional parameters and ECM molecules during the cardiac remodeling that occurs during pregnancy and the first postpartum month. Heart weights normalized to tibia lengths were increased in Timp4 knockout (Timp4 KO) females compared to wildtypes. Serial echocardiography was performed on pregnancy days (eds) 10, 12, 18 and postpartum days (ppds) 2, 7, 14, 21, and 28 and revealed that both wildtype and Timp4 KO mice increased end systolic and end diastolic volumes (ESV, EDV) by mid to late pregnancy compared to virgins, with EDV changes persisting through the postpartum period. Compared to wildtypes, Timp4 KO mice exhibited lower ESV in virgins and on most pregnancy and postpartum days, whereas EDV was lower at pregnancy days 12 and 18 and ppd28. Ejection fraction was higher in Timp4 KO mice for almost all days, compared to wildtypes. High molecular weight forms of COL1A1 and COL3A1 proteins in LV were elevated in Timp4 KO virgins, and COL1A1 was higher at ed18 and ppd2 compared to wildtypes. Timp4 KO mice during late pregnancy and on most postpartum days were able to maintain stroke volume similar to wildtype mice through increased ejection fraction.
Guarda su PubMed
-
Assessment of fluid status in neonatal dialysis: the need for new tools.
Pediatr Nephrol2022 Dec;():. doi: 10.1007/s00467-022-05829-2.
Nourbakhsh Noureddin, Benador Nadine,
Abstract
BACKGROUND:
Assessment of fluid status in neonatal dialysis has largely focused on traditional tools including clinical assessment, serial weights, and blood pressure (BP) measurements. However, in infants on kidney replacement therapy, the assessment of fluid overload is problematic due to errors in weight assessment, subtlety of physical exam findings, and inaccuracy of non-invasive BP measurements. In this presentation of a neonate with bilateral renal agenesis requiring kidney replacement therapy, the treating team assessed a number of variables in determining the ultrafiltration prescription for dialysis across 2 modalities (hemodialysis and continuous kidney replacement therapy).
COMPLICATIONS:
Fluid overload, cardiomegaly, and worsened respiratory status occurred when attempting to assess the neonate's fluid status by traditional markers (weights, blood pressures, physical exam findings). B-type natriuretic peptide (BNP) was obtained and was noted to correlate with the degree of fluid overload.
KEY MANAGEMENT POINTS:
Compared to traditional tools for assessment of fluid status in pediatric dialysis, BNP assisted the medical team in optimizing the volume status of the subject and determining optimal daily ultrafiltration goals. Due to the rapid release in response to myocardial stretch and the lack of kidney clearance of the peptide, BNP may represent an objective, timely, and reliable index of volume status in the pediatric dialysis patient.
© 2022. The Author(s).
Guarda su PubMed
-
Melatonin ameliorates myocardial infarction in obese diabetic individuals: the possible involvement of macrophage apoptotic factors.
J Pineal Res2022 Dec;():. doi: 10.1111/jpi.12847.
Maity Juin, Dey Tiyasa, Banerjee Adrita, Chattopadhyay Aindrila, Das Asish R, Bandyopadhyay Debasish,
Abstract
In recent days, the hike in obesity mediated epidemic across the globe and prevalence of obesity induced cardiovascular disease (CVD) has become one of the chief grounds of morbidity and mortality. This epidemic driven detrimental events in the cardiac tissues starts with the altered distribution and metabolism pattern of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on arterial wall and atherosclerotic plaque generation, followed by vascular spasm and infarction. Subsequently, obesity triggered metabolic malfunction induce free radical generation which may further trigger pro-inflammatory signalling and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) transcriptional factor, thus inducing interferon-gamma (IFN-?), tumour necrosis factor-alpha (TNF-?), and inducible nitric oxide synthase (iNOS). This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby turning the obese diabetic patients prone towards the development of myocardial infarction or stroke in comparison to their non diabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals causes progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation (LPO), pro-inflammatory reactions, thereby resolving free radical induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol (TC) concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity induced acute myocardial infarction (AMI). This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity- diabetes correlation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Ultrasonic Texture Features for Assessing Cardiac Remodeling and Dysfunction.
J Am Coll Cardiol2022 Dec;80(23):2187-2201. doi: 10.1016/j.jacc.2022.09.036.
Hathaway Quincy A, Yanamala Naveena, Siva Nanda K, Adjeroh Donald A, Hollander John M, Sengupta Partho P,
Abstract
BACKGROUND:
Changes in cardiac size, myocardial mass, cardiomyocyte appearance, and, ultimately, the function of the entire organ are interrelated features of cardiac remodeling that profoundly affect patient outcomes.
OBJECTIVES:
This study proposes that the application of radiomics for extracting cardiac ultrasonic textural features (ultrasomics) can aid rapid, automated assessment of left ventricular (LV) structure and function without requiring manual measurements.
METHODS:
This study developed machine-learning models using cardiac ultrasound images from 1,915 subjects in 3 clinical cohorts: 1) an expert-annotated cardiac point-of-care-ultrasound (POCUS) registry (n = 943, 80% training/testing and 20% internal validation); 2) a prospective POCUS cohort for external validation (n = 275); and 3) a prospective external validation on high-end ultrasound systems (n = 484). In a type 2 diabetes murine model, echocardiography of wild-type (n = 10) and Leptr (n = 8) mice were assessed longitudinally at 3 and 25 weeks, and ultrasomics features were correlated with histopathological features of hypertrophy.
RESULTS:
The ultrasomics model predicted LV remodeling in the POCUS and high-end ultrasound external validation studies (area under the curve: 0.78 [95% CI: 0.68-0.88] and 0.79 [95% CI: 0.73-0.86], respectively). Similarly, the ultrasomics model predicted LV remodeling was significantly associated with major adverse cardiovascular events in both cohorts (P
CONCLUSIONS:
Cardiac ultrasomics-based biomarkers may aid development of machine-learning models that provide an expert-level assessment of LV structure and function.
Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Guarda su PubMed
-
A Narrative Review of the Pathophysiology and Treatment of Hypertrophic Cardiomyopathy.
South Med J2022 Dec;115(12):926-929. doi: 10.14423/SMJ.0000000000001478.
Gelpi Acevedo Lee M, Salinas Alexandra Lizette, Polanco Juan Sebastian, Nizami Hamasah, Marsh Denise, Patel Meet, Parikh Kinna, Jain Rahul, Jain Rohit,
Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic autosomal dominant disorder of the heart muscle that is characterized by left ventricular hypertrophy and sudden cardiac death. It is the most common inherited cardiac disease. HCM is defined by sarcomeric mutations that result in fibrosis of the heart, affecting contraction. In most cases, clinical presentations can range from asymptomatic to systolic and diastolic ventricular dysfunction, arrhythmias, and sudden cardiac death. Some histopathologic features typical of the disease are changes in myocyte disarray and myocardial fibrosis. Mutations in the ?-myosin heavy chain and myosin-binding protein C have been identified as the cause of the disease. The goals of pharmacological therapy as well as nonpharmacological therapy are to alleviate the symptoms and to prevent sudden cardiac death. Anatomical defects are treated primarily by surgical intervention, whereas other issues such as hypercontractility are treated with pharmacotherapy. In this article, we review the pathophysiology and treatment options for HCM.
Guarda su PubMed
-
Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults.
PLoS One2022 ;17(12):e0278308. doi: 10.1371/journal.pone.0278308.
Snel Gert J H, Slart Riemer H J A, Velthuis Birgitta K, van den Boomen Maaike, Nguyen Christopher T, Sosnovik David E, van Deursen Vincent M, Dierckx Rudi A J O, Borra Ronald J H, Prakken Niek H J,
Abstract
In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.
Copyright: © 2022 Snel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Guarda su PubMed
-
RBM24 controls cardiac QT interval through CaMKII? splicing.
Cell Mol Life Sci2022 Dec;79(12):613. doi: 10.1007/s00018-022-04624-4.
Liu Jing, Wang Ke, Liu Xingyang, Pan Lei, Zhou Wanlu, Huang Jingru, Liu Hongli, Su Zhiying, Xu Xiu Qin,
Abstract
Calcium/calmodulin-dependent kinase II delta (CaMKII?) is the predominant cardiac isoform and it is alternatively spliced to generate multiple variants. Variable variants allow for distinct localization and potentially different functions in the heart. Dysregulation of CaMKII? splicing has been demonstrated to be involved in the pathogenesis of heart diseases, such as cardiac hypertrophy, arrhythmia, and diastolic dysfunction. However, the mechanisms that regulate CaMKII? are incompletely understood. Here, we show that RNA binding motif protein 24 (RBM24) is a key splicing regulator of CaMKII?. RBM24 ablation leads to the aberrant shift of CaMKII? towards the ?-C isoform, which is known to activate the L-type Ca current. In line with this, we found marked alteration in Ca handling followed by prolongation of the ventricular cardiac action potential and QT interval in RBM24 knockout mice, and these changes could be attenuated by treatment with an inhibitor of CaMKII?. Importantly, knockdown of RBM24 in human embryonic stem cell-derived cardiomyocytes showed similar electrophysiological abnormalities, suggesting the important role of RBM24 in the human heart. Thus, our data suggest that RBM24 is a critical regulator of CaMKII? to control the cardiac QT interval, highlighting the key role of splicing regulation in cardiac rhythm.
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Guarda su PubMed
-
Genome Editing and Pathological Cardiac Hypertrophy.
Adv Exp Med Biol2023 ;1396():87-101. doi: 10.1007/978-981-19-5642-3_6.
Kato Takao,
Abstract
Three major genome editing tools, transcription activator-like effector nucleases (TALENs), zinc finger nucleases (ZFNs), and clustered regularly interspaced short palindromic repeat (CRISPR) systems, are increasingly important technologies used in the study and treatment of hereditary myocardial diseases. Germ cell genome editing and modification can permanently eliminate monogenic cardiovascular disease from the offspring of affected families and the next generation, although ethically controversial. Somatic genome editing may be a promising method for the treatment of hereditary cardiomyopathy various diseases for which gene knockout is favorable and can also treat people who are already ill, although there are currently some technical challenges. This chapter describes the application of genome editing in the experimental studies and treatment of hypertrophic cardiomyopathy as well as other cardiomyopathies.
© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
Guarda su PubMed
-
Prohibitin1 maintains mitochondrial quality in Isoproterenol-Induced Cardiac Hypertrophy in H9C2 cells.
Biol Cell2022 Dec;():. doi: 10.1111/boc.202200094.
Chakrabarti Moumita, Raut Ganesh Kumar, Jain Nishant, Bhadra Manika Pal,
Abstract
Various types of stress initially induce a state of 'Cardiac Hypertrophy (CH) in the heart. But, persistent escalation of cardiac stress leads to progression from an adaptive physiological to a maladaptive pathological state. So, elucidating molecular mechanisms that can attenuate CH is imperative in developing cardiac therapies. Previously, we showed that Prohibitin1 (PHB1) has a protective role in CH-induced oxidative stress. Nevertheless, it is unclear how PHB1, a mitochondrial protein, has a protective role in CH. Therefore, we hypothesized that PHB1 maintains mitochondrial quality in CH. To test this hypothesis, we used Isoproterenol (ISO) to induce CH in H9C2 cells overexpressing PHB1 and elucidated mitochondrial quality control pathways. We found that overexpressing PHB1 attenuates ISO-induced CH and restores mitochondrial morphology in H9C2 cells. In addition, PHB1 blocks the pro-hypertrophic IGF1R/AKT pathway and restores the mitochondrial membrane polarization in ISO-treated cells. We observed that overexpressing PHB1 promotes mitochondrial biogenesis, improves mitochondrial respiratory capacity, and triggers mitophagy. We conclude that PHB1 maintains mitochondrial quality in ISO-induced CH in H9C2 cells. Based on our results, we suggest that small molecules that induce PHB1 in cardiac cells may prove beneficial in developing cardiac therapies. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Case Report: Novel LIM domain-binding protein 3 (LDB3) mutations associated with hypertrophic cardiomyopathy family.
Front Pediatr2022 ;10():947963. doi: 947963.
Zheng Junmin, Huang Zhuangzhuang, Hou Shan, Jiang Xunwei, Zhang Yongwei, Liu Wei, Jia Jia, Li Yun, Sun Xiaomin, Xie Lijian, Zhao Xiaopei, Hou Cuilan, Xiao Tingting,
Abstract
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of -0.9211 and -0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.
© 2022 Zheng, Huang, Hou, Jiang, Zhang, Liu, Jia, Li, Sun, Xie, Zhao, Hou and Xiao.
Guarda su PubMed
-
UEDA Heart Awards for 2022.
Int Heart J2022 ;63(6):1217. doi: 10.1536/ihj.63-6_UEDA.
Abstract
We are pleased to announce that the following 3 articles have been selected for the UEDA Heart Awards for the Year 2022.FIRST PLACEChronic HDAC6 Activation Induces Atrial Fibrillation Through Atrial Electrical and Structural Remodeling in Transgenic MiceYohei Sawa, Naoko Matsushita, Sachiko Sato, Nanae Ishida, Maki Saito, Atsushi Sanbe, Yoshihiro Morino, Eiichi Taira, Mami Obara, Masamichi HiroseInt Heart J 2021; 62 (3): 616-626.SECOND PLACEA Novel Titin Truncation Variant Linked to Familial Dilated Cardiomyopathy Found in a Japanese Family and Its Functional Analysis in Genome-Edited Model CellsKayoko Hirayama-Yamada, Natsuko Inagaki, Takeharu Hayashi, Akinori KimuraInt Heart J 2021; 62 (2): 359-366.THIRD PLACECytokine Signaling and Matrix Remodeling Pathways Associated with Cardiac Sarcoidosis Disease Activity Defined Using FDG PET ImagingBryan D. Young, Hannah Moreland, Kelsie E. Oatmen, Lisa A. Freeburg, Zartashia Shahab, Erica Herzog, Edward J. Miller, Francis G. SpinaleInt Heart J 2021; 62 (5): 1096-1105.
Guarda su PubMed
