keyword
https://read.qxmd.com/read/38533084/forward-genetic-screen-using-a-gene-breaking-trap-approach-identifies-a-novel-role-of-grin2bb-associated-rna-transcript-grin2bbart-in-zebrafish-heart-function
#1
JOURNAL ARTICLE
Ramcharan Singh Angom, Adita Joshi, Ashok Patowary, Ambily Sivadas, Soundhar Ramasamy, Shamsudheen K V, Kriti Kaushik, Ankit Sabharwal, Mukesh Kumar Lalwani, Subburaj K, Naresh Singh, Vinod Scaria, Sridhar Sivasubbu
LncRNA-based control affects cardiac pathophysiologies like myocardial infarction, coronary artery disease, hypertrophy, and myotonic muscular dystrophy. This study used a gene-break transposon (GBT) to screen zebrafish ( Danio rerio ) for insertional mutagenesis. We identified three insertional mutants where the GBT captured a cardiac gene. One of the adult viable GBT mutants had bradycardia (heart arrhythmia) and enlarged cardiac chambers or hypertrophy; we named it "bigheart." Bigheart mutant insertion maps to grin2bb or N-methyl D-aspartate receptor (NMDAR2B) gene intron 2 in reverse orientation...
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38453702/a-real-world-pharmacovigilance-study-investigating-the-toxicities-of-histone-deacetylase-inhibitors
#2
JOURNAL ARTICLE
Wenjie Li, Yiming Fu, Wei Wang
Histone deacetylase (HDAC) inhibitors are emerging as promising treatments for hematological malignancies, with potential applications extending to solid tumors in the future. Given their wide-ranging biological effects, there is a pressing need for a thorough understanding of the toxicities linked to HDAC inhibition. In this study, a pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System database. Suspected adverse events linked to HDAC inhibitors were detected through various statistical methodologies, including reporting odds ratio, proportional reporting ratio, information component, and Empirical Bayes Geometric Mean...
March 8, 2024: Annals of Hematology
https://read.qxmd.com/read/37759673/emodin-inhibited-pathological-cardiac-hypertrophy-in-response-to-angiotensin-induced-hypertension-and-altered-the-gut-microbiome
#3
JOURNAL ARTICLE
Levi Evans, Tori Price, Nathaniel Hubert, Julia Moore, Yiqui Shen, Maheshi Athukorala, Steven Frese, Kristina Martinez-Guryn, Bradley S Ferguson
OBJECTIVE: Evidence suggests that food bioactives affect the epigenome to prevent pathological cardiac hypertrophy. Recently, we showed that emodin, an anthraquinone, attenuated pathological cardiac hypertrophy and histone deacetylase (HDAC) activity. However, we only examined the cardioprotective effects of emodin's parent compound and not those of emodin metabolites or of emodin-gut microbiome interactions. The microbiome has emerged as a key player in chronic diseases such as metabolic and cardiac disease...
August 22, 2023: Biomolecules
https://read.qxmd.com/read/37711853/sin3a-associated-protein-130%C3%A2-kda-sap130-plays-an-evolutionary-conserved-role-in-zebrafish-heart-development
#4
JOURNAL ARTICLE
Ricardo A DeMoya, Rachel E Forman-Rubinsky, Deon Fontaine, Joseph Shin, Simon C Watkins, Cecilia W Lo, Michael Tsang
Hypoplastic left heart syndrome (HLHS) is a congenital heart disease where the left ventricle is reduced in size. A forward genetic screen in mice identified SIN3A associated protein 130 kDa ( Sap130 ), part of the chromatin modifying SIN3A/HDAC complex, as a gene contributing to the etiology of HLHS. Here, we report the role of zebrafish sap130 genes in heart development. Loss of sap130a, one of two Sap130 orthologs, resulted in smaller ventricle size, a phenotype reminiscent to the hypoplastic left ventricle in mice...
2023: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/37567457/the-novel-peptide-athycaltide-1-attenuates-ang-ii-induced-pathological-myocardial-hypertrophy-by-reducing-ros-and-inhibiting-the-activation-of-camkii-and-erk1-2
#5
JOURNAL ARTICLE
Xi Zheng, Fuxiang Su, Ming Lei, Jingyuan Li, Chenyang Zhang, Yujia Zhang, Ming Wei, Wei Li, Sichong Chen, Yunzhu Liu, Qinghua Gao, Liying Hao
Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology...
August 9, 2023: European Journal of Pharmacology
https://read.qxmd.com/read/37471486/cardiac-fibrosis-mitigated-by-an-endogenous-negative-regulator-of-hdac
#6
EDITORIAL
Michael P Lazaropoulos, John W Elrod
No abstract text is available yet for this article.
July 21, 2023: Circulation Research
https://read.qxmd.com/read/37461108/unraveling-the-epigenetic-landscape-of-pulmonary-arterial-hypertension-implications-for-personalized-medicine-development
#7
REVIEW
Jaydev Dave, Vineeta Jagana, Radoslav Janostiak, Malik Bisserier
Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes...
July 17, 2023: Journal of Translational Medicine
https://read.qxmd.com/read/37386838/psme4-determines-mesenchymal-stem-cell-fate-towards-cardiac-commitment-through-yap1-degradation
#8
JOURNAL ARTICLE
Mira Kim, Yong Sook Kim, Youngkeun Ahn, Gwang Hyeon Eom, Somy Yoon
The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process...
July 1, 2023: Korean Journal of Physiology & Pharmacology
https://read.qxmd.com/read/37245797/gut-derived-short-chain-fatty-acids-bridge-cardiac-and-systemic-metabolism-and-immunity-in-heart-failure
#9
REVIEW
Anzhu Wang, Zhendong Li, Zhuo Sun, Dawu Zhang, Xiaochang Ma
Heart failure (HF) represents a group of complex clinical syndromes with high morbidity and mortality and has a significant global health burden. Inflammation and metabolic disorders are closely related to the development of HF, which are complex and depend on the severity and type of HF and common metabolic comorbidities such as obesity and diabetes. An increasing body of evidence indicates the importance of short-chain fatty acids (SCFAs) in regulating cardiac function. In addition, SCFAs represent a unique class of metabolites and play a distinct role in shaping systemic immunity and metabolism...
May 26, 2023: Journal of Nutritional Biochemistry
https://read.qxmd.com/read/37224740/targeting-histone-deacetylases-for-heart-diseases
#10
REVIEW
Gang Jin, Kaiyue Wang, Yaohui Zhao, Shuo Yuan, Zhangxu He, Jingyu Zhang
Histone deacetylases (HDACs) are responsible for the deacetylation of lysine residues in histone or non-histone substrates, leading to the regulation of many biological functions, such as gene transcription, translation and remodeling chromatin. Targeting HDACs for drug development is a promising way for human diseases, including cancers and heart diseases. In particular, numerous HDAC inhibitors have revealed potential clinical value for the treatment of cardiac diseases in recent years. In this review, we systematically summarize the therapeutic roles of HDAC inhibitors with different chemotypes on heart diseases...
May 10, 2023: Bioorganic Chemistry
https://read.qxmd.com/read/37086972/the-role-of-p21-activated-kinase-pak1-in-sinus-node-function
#11
JOURNAL ARTICLE
Carlos H Pereira, Dan J Bare, Paola C Rosas, Fernando A L Dias, Kathrin Banach
Sinoatrial node (SAN) dysfunction (SND) and atrial arrhythmia frequently occur simultaneously with a hazard ratio of 4.2 for new onset atrial fibrillation (AF) in SND patients. In the atrial muscle attenuated activity of p21-activated kinase 1 (Pak1) increases the risk for AF by enhancing NADPH oxidase 2 dependent production of reactive oxygen species (ROS). However, the role of Pak1 dependent ROS regulation in SAN function has not yet been determined. We hypothesize that Pak1 activity maintains SAN activity by regulating the expression of the hyperpolarization activated cyclic nucleotide gated cation channel (HCN)...
April 20, 2023: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/36980194/emerging-roles-of-sirt5-in-metabolism-cancer-and-sars-cov-2-infection
#12
REVIEW
Emanuele Fabbrizi, Francesco Fiorentino, Vincenzo Carafa, Lucia Altucci, Antonello Mai, Dante Rotili
Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD+ -dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activity of proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty acid oxidation, electron transport chain, generation of ketone bodies, nitrogenous waste management, and reactive oxygen species (ROS) detoxification...
March 9, 2023: Cells
https://read.qxmd.com/read/36936452/protective-effect-of-hdacis-in-improves-survival-and-organ-injury-after-clp-induced-sepsis
#13
JOURNAL ARTICLE
Kunwei Niu, Shibin Qu, Long Yang, Hong Zhang, Juzheng Yuan, Hanlu Fan, Xiao Li, Kaishan Tao
INTRODUCTION: The effects of isoform-specific histone deacetylase inhibitors (HDACIs) and the non-selective HDACI on sepsis have been profoundly reported. However, the best HDAC classes have not been fully evaluated. Therefore, this study aimed to determine which HDACIs are responsible for survival and beneficial for organ injury. METHODS: Experiment I, SD rats were subjected to cecal ligation and puncture and randomly assigned to the no treatment, dimethyl sulfoxide (DMSO) only, MS-275, LMK-235, tubastatinA (TubA), trichostatin-A (TSA), and sirtinol groups (n = 5)...
March 2023: Surgery open science
https://read.qxmd.com/read/36927982/knockdown-of-hdac9-attenuates-sepsis-induced-myocardial-injury-and-inflammatory-response
#14
JOURNAL ARTICLE
Long Yang, Chunxue Wu, Ying Cui, Shimin Dong
Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased LVEDD and LVESD, and increased FS% and EF%...
March 13, 2023: Experimental Animals
https://read.qxmd.com/read/36889378/the-role-of-histone-deacetylases-in-cardiac-energy-metabolism-in-heart-diseases
#15
REVIEW
Qingwen Yu, Guangyuan Zhao, Jingjing Liu, Yajie Peng, Xueli Xu, Fei Zhao, Yangyang Shi, Chengyun Jin, Ji Zhang, Bo Wei
Heart diseases are associated with substantial morbidity and mortality worldwide. The underlying mechanisms and pathological changes associated with cardiac diseases are exceptionally complex. Highly active cardiomyocytes require sufficient energy metabolism to maintain their function. Under physiological conditions, the choice of fuel is a delicate process that depends on the whole body and organs to support the normal function of heart tissues. However, disordered cardiac metabolism has been discovered to play a key role in many forms of heart diseases, including ischemic heart disease, cardiac hypertrophy, heart failure, and cardiac injury induced by diabetes or sepsis...
March 6, 2023: Metabolism: Clinical and Experimental
https://read.qxmd.com/read/36883446/integrated-proteomics-unveils-nuclear-pde3a2-as-a-regulator-of-cardiac-myocyte-hypertrophy
#16
JOURNAL ARTICLE
Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J R Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
BACKGROUND: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing. METHODS: Here, we combined an integrated phosphoproteomics approach that takes advantage of the unique role that individual PDEs play in the control of local cAMP, with network analysis to identify previously unrecognized cAMP nanodomains associated with β-adrenergic stimulation...
March 8, 2023: Circulation Research
https://read.qxmd.com/read/36763507/calcium-stress-adds-a-third-hit-in-driving-heart-failure-with-preserved-ejection-fraction
#17
JOURNAL ARTICLE
Kyohei Fujita, Matthew Ellis, Farah Sheikh
No abstract text is available yet for this article.
February 10, 2023: American Journal of Physiology. Heart and Circulatory Physiology
https://read.qxmd.com/read/36763506/combining-three-independent-pathological-stressors-induces-a-heart-failure-with-preserved-ejection-fraction-phenotype
#18
JOURNAL ARTICLE
Yijia Li, Hajime Kubo, Daohai Yu, Yijun Yang, Jaslyn P Johnson, Deborah M Eaton, Remus M Berretta, Michael Foster, Timothy A McKinsey, Jun Yu, John W Elrod, Xiongwen Chen, Steven R Houser
INTRODUCTION: Heart failure (HF) with preserved ejection fraction (HFpEF) is defined as HF with an Ejection Fraction (EF) ≥50% and elevated cardiac diastolic filling pressures. The underlying causes of HFpEF are multifactorial and not well-defined. A transgenic mouse with low levels of cardiomyocyte (CM)-specific inducible Cavβ2a expression (β2a-Tg mice) showed increased cytosolic CM Ca2+ , and modest levels of CM hypertrophy, and fibrosis. This study aimed to determine if β2a-Tg mice develop a HFpEF phenotype when challenged with two additional stressors, high-fat diet (HFD) and L-NAME (LN)...
February 10, 2023: American Journal of Physiology. Heart and Circulatory Physiology
https://read.qxmd.com/read/36753565/metabolic-reprogramming-by-immune-responsive-gene-1-up-regulation-improves-donor-heart-preservation-and-function
#19
JOURNAL ARTICLE
Ienglam Lei, Wei Huang, Pierre Emmanuel Noly, Suyash Naik, Miriyam Ghali, Liu Liu, Francis D Pagani, Ashraf Abou El Ela, Jordan S Pober, Bertram Pitt, Jeffrey L Platt, Marilia Cascalho, Zhong Wang, Y Eugene Chen, Richard M Mortensen, Paul C Tang
Preservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization. Here, we showed that metabolic reprogramming through up-regulation of the enzyme immune response gene 1 (IRG1) and its product itaconate improved heart function after prolonged preservation. Irg1 transcript induction was achieved by adding the histone deacetylase (HDAC) inhibitor valproic acid (VPA) to a histidine-tryptophan-ketoglutarate solution used for donor heart preservation...
February 8, 2023: Science Translational Medicine
https://read.qxmd.com/read/36579524/short-chain-fatty-acids-in-gut-heart-axis-their-role-in-the-pathology-of-heart-failure
#20
REVIEW
Midori Yukino-Iwashita, Yuji Nagatomo, Akane Kawai, Akira Taruoka, Yusuke Yumita, Kazuki Kagami, Risako Yasuda, Takumi Toya, Yukinori Ikegami, Nobuyuki Masaki, Yasuo Ido, Takeshi Adachi
Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on the pathology of a variety of diseases. The changes of SCFA concentration were reported to be observed in various cardiovascular diseases including HF in experimental animals and humans. HF causes hypoperfusion and/or congestion in the gut, which may lead to lowered production of SCFAs, possibly through the pathological changes of the gut microenvironment including microbiota composition...
November 1, 2022: Journal of Personalized Medicine
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