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Cardiac hypertrophy

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https://www.readbyqxmd.com/read/28550180/a-novel-de-novo-mutation-in-prkag2-gene-infantile-onset-phenotype-and-signaling-pathway-involved
#1
Yanchun Xu, Alex Gray, David Grahame Hardie, Alper Uzun, Sunil Shaw, James F Padbury, Chanika Phornphutkul, Yi-Tang Tseng
PRKAG2 encodes the γ2-subunit isoform of the 5' AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved and therapeutic options for K475E mutation using cells stably expressing human wild type (WT) or the K475E mutant...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550173/experimental-cardiac-radiation-exposure-induces-ventricular-diastolic-dysfunction-with-preserved-ejection-fraction
#2
Hirofumi Saiki, Gilles Moulay, Adam J Guenzel, Weibin Liu, Teresa Decklever, Kelly Classic, Linh Pham, Horng H Chen, John C Burnett, Stephen J Russell, Margaret M Redfield
BACKGROUND: Breast cancer radiotherapy increases the risk of heart failure (HF) with preserved ejection fraction (HFpEF). Cardiomyocytes are highly radio-resistant but radiation specifically affects coronary microvascular endothelial cells with subsequent microvascular inflammation and rarefaction. The effects of radiation on left ventricular (LV) diastolic function are poorly characterized. We hypothesized that cardiac radiation exposure may result in diastolic dysfunction without reduced EF...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#3
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28549111/diabetic-db-db-mice-do-not-develop-heart-failure-upon-pressure-overload-a-longitudinal-in-vivo-pet-mri-and-mrs-study-on-cardiac-metabolic-structural-and-functional-adaptations
#4
Desiree Abdurrachim, Miranda Nabben, Verena Hoerr, Michael T Kuhlmann, Philipp Bovenkamp, Jolita Ciapaite, Ilvy M E Geraets, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Michael Schäfers, Klaas Nicolay, Cornelius Faber, Sven Hermann, Jeanine J Prompers
Aim: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Methods and results: Transverse aortic constriction (TAC) was performed in non-diabetic ( db /+) and diabetic ( db/db ) mice to induce pressure overload...
May 26, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28549058/histone-deacetylase-adaptation-in-single-ventricle-heart-disease-and-a-young-animal-model-of-right-ventricular-hypertrophy
#5
Weston W Blakeslee, Kimberly M Demos-Davies, Douglas D Lemon, Katharina M Lutter, Maria A Cavasin, Sam Payne, Karin Nunley, Carlin S Long, Timothy A McKinsey, Shelley D Miyamoto
BACKGROUNDHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac disease. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle heart disease of right ventricular morphology (SV), as well as in a rodent model of right ventricular hypertrophy (RVH).METHODSHomogenates of RV explants from non-failing controls and SV children were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day old rat pups were placed in hypoxic conditions and echocardiographic analysis, gene expression, HDAC catalytic activity and isoform expression studies of the RV were performed...
May 26, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28548932/lncrna-tincr-attenuates-cardiac-hypertrophy-by-epigenetic-silencing-of-camkii
#6
Mingjing Shao, Guangdong Chen, Fengli Lv, Yanyan Liu, Hongjun Tian, Ran Tao, Ronghuan Jiang, Wei Zhang, Chuanjun Zhuo
In the previous study, we established a mouse model of cardiac hypertrophy using transverse aortic constriction (TAC) and found that the expression of long non-coding RNAs TINCR was downregulated in myocardial tissue. The present study was designed to determine the potential role of TINCR in the pathogenesis of cardiac hypertrophy. Our results showed that enforced expression of TINCR could attenuate cardiac hypertrophy in TAC mice. Angiotensin II (Ang-II) was found to be associated with reduced TINCR expression and increased hypertrophy in cultured neonatal cardiomyocytes...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548229/endoplasmic-reticulum-stress-in-the-heart-the-insights-into-mechanisms-and-drug-targets
#7
REVIEW
Shunyao Wang, Pablo Binder, Qiru Fang, Zhenzhong Wang, Wei Xiao, Wei Liu, Xin Wang
The endoplasmic reticulum (ER) serves several essential cellular functions including protein synthesis, protein folding, protein translocation, calcium homoeostasis and lipid biosynthesis. Physiological or pathological stimuli which disrupt ER homoeostasis and disturb its functions lead to an accumulation of misfolded and unfolded proteins, a condition referred to as ER stress. ER stress triggers unfolded protein response (UPR) to restore the homoeostasis of ER through activating transcriptional and translational pathways...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28548091/cellular-interplay-via-cytokine-hierarchy-causes-pathological-cardiac-hypertrophy-in-raf1-mutant-noonan-syndrome
#8
Jiani C Yin, Mathew J Platt, Xixi Tian, Xue Wu, Peter H Backx, Jeremy A Simpson, Toshiyuki Araki, Benjamin G Neel
Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1(L613V/+) knock-in mice. Here, using inducible Raf1(L613V) expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1(L613V) enhances Ca(2+) sensitivity and cardiac contractility without causing hypertrophy...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28546535/a-novel-prkag2-mutation-in-a-chinese-family-with-cardiac-hypertrophy-and-ventricular-pre-excitation
#9
Kun-Qi Yang, Chao-Xia Lu, Ying Zhang, Yan-Kun Yang, Jia-Cheng Li, Tian Lan, Xu Meng, Peng Fan, Tao Tian, Lin-Ping Wang, Ya-Xin Liu, Xue Zhang, Xian-Liang Zhou
PRKAG2 syndrome is a rare autosomal dominant inherited disorder that is characterized by cardiac hypertrophy, ventricular pre-excitation and conduction system abnormalities. There is little knowledge in cardiovascular magnetic resonance (CMR) characteristics of PRKAG2 cardiomyopathy. This study investigated the genetic defect in a three-generation Chinese family with cardiac hypertrophy and ventricular pre-excitation using whole-exome sequencing. A novel missense mutation, c.1006 G > T (p.V336L), was identified in PRKAG2...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546047/an-impedance-based-approach-using-human-ipsc-derived-cardiomyocytes-significantly-improves-in-vitro-prediction-of-in-vivo-cardiotox-liabilities
#10
Bryan Koci, Gregory Luerman, Anika Duenbostell, Ralf Kettenhofen, Heribert Bohlen, Luke Coyle, Brian Knight, Warren Ku, Walter Volberg, Joseph R Woska, Martha P Brown
Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time...
May 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28545342/echocardiographic-and-clinical-findings-in-patients-with-fabry-disease-during-long-term-enzyme-replacement-therapy-a-nationwide-danish-cohort-study
#11
Christoffer Valdorff Madsen, Henning Bundgaard, Åse Krogh Rasmussen, Søren Schwartz Sørensen, Jørgen Holm Petersen, Lars Køber, Ulla Feldt-Rasmussen, Helle Petri
OBJECTIVES: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT. METHODS: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort...
May 25, 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/28544034/knock-down-of-farnesyl-pyrophosphate-synthase-protects-heart-derived-h9c2-cells-against-hypoxia-reoxygenation-induced-injury
#12
Dong-Pu Dai, Huan-Dong Wu, Jian Yang, Shi-Zhen Shen, Chen-Ze Zhao, Jie Ding, Shen-Jiang Hu
Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. Our previous studies have indicated that cardiac-specific overexpression of FPPS induces cardiac hypertrophy and dysfunction in mice, and inhibition of FPPS prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. However, the role for FPPS in myocardial ischemia/reperfusion (MIR) injury is still not clear. The objective of this work was to investigate the effect of FPPS on MIR injury in H9c2 cells which were subjected to hypoxia/reoxygenation (HR) to mimic MIR...
May 24, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28542952/compensatory-and-decompensatory-alterations-in-cardiomyocyte-ca-2-dynamics-in-hearts-with-diastolic-dysfunction-following-aortic-banding
#13
Sara Gattoni, Åsmund Treu Røe, Jan Magnus Aronsen, Ivar Sjaastad, William E Louch, Nicolas P Smith, Steven A Niederer
KEY POINTS: At the cellular level cardiac hypertrophy causes remodelling, leading to changes in ionic channel, pump and exchanger densities and kinetics. Previous studies have focused on quantifying changes in channels, pumps and exchangers without quantitatively linking these changes with emergent cellular scale functionality. Two biophysical cardiac cell models were created, parameterized and validated and are able to simulate electrophysiology and calcium dynamics in myocytes from control sham operated rats and aortic-banded rats exhibiting diastolic dysfunction...
May 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28542596/progressive-mitochondrial-protein-lysine-acetylation-and-heart-failure-in-a-model-of-friedreich-s-ataxia-cardiomyopathy
#14
Amanda R Stram, Gregory R Wagner, Brian D Fogler, P Melanie Pride, Matthew D Hirschey, R Mark Payne
INTRODUCTION: The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury...
2017: PloS One
https://www.readbyqxmd.com/read/28541499/hypertension-and-cardiac-arrhythmias-executive-summary-of-a-consensus-document-from-the-european-heart-rhythm-association-ehra-and-esc-council-on-hypertension-endorsed-by-the-heart-rhythm-society-hrs-asia-pacific-heart-rhythm-society-aphrs-and-sociedad-latinoamericana
#15
Gregory Y H Lip, Antonio Coca, Thomas Kahan, Giuseppe Boriani, Antonis S Manolis, Michael Hecht Olsen, Ali Oto, Tatjana S Potpara, Jan Steffel, Francisco Marín, Márcio Jansen de Oliveira Figueiredo, Giovanni de Simone, Wendy S Tzou, Chern En Chiang, Bryan Williams
Hypertension (HTN) is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease (CAD), stroke, peripheral artery disease and chronic renal failure. Hypertensive heart disease can manifest as many types of cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in HTN patients, especially in those with left ventricular hypertrophy (LVH), CAD or HF. In addition, high doses of thiazide diuretics commonly used to treat hypertension, may result in electrolyte abnormalities (eg...
May 25, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/28539827/traditional-chinese-medication-qiliqiangxin-protects-against-cardiac-remodeling-and-dysfunction-in-spontaneously-hypertensive-rats
#16
Hui Wang, Xiaomin Zhang, Pujiao Yu, Qiulian Zhou, Jialiang Zhang, Haifeng Zhang, Hongsheng Zhu, Chenlin Zhang, Wenming Yao, Lin Che, Jiahong Xu, Yihua Bei, Xinli Li
Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28537760/caveolin-1-autophagy-pathway-mediated-cardiomyocyte-hypertrophy-induced-by-apelin-13
#17
Di Wu, Feng Xie, Ling Xiao, Fen Feng, Shifang Huang, Lu He, Meiqing Liu, Qun Zhou, Lanfang Li, Linxi Chen
Apelin, an endogenous ligand for apelin receptor (APJ), is reported to be involved in cardiomyocyte hypertrophy. In this study, we explored the mechanism of cardiomyocyte hypertrophy induced by apelin-13/APJ system. Left ventricular hypertrophy (LVH) rat model was established by constricting the abdominal aorta. Western blots were used for protein expression in LVH rats and cultured H9c2 cardiomyocytes. Transmission electron microscopy (TEM) was used to monitor morphological features of cells. In addition, the diameter and volume of H9c2 cells were detected by Scepter™ Handheld Automated Cell Counter...
May 24, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28537040/accuracy-of-99mtc-hydroxymethylene-diphosphonate-scintigraphy-for-diagnosis-of-transthyretin-cardiac-amyloidosis
#18
Francesco Cappelli, Chiara Gallini, Carlo Di Mario, Egidio Natalino Costanzo, Luca Vaggelli, Francesca Tutino, Alfonso Ciaccio, Simone Bartolini, Paola Angelotti, Sabrina Frusconi, Silvia Farsetti, Giuseppe Vergaro, Assuero Giorgetti, Paolo Marzullo, Dario Genovesi, Michele Emdin, Federico Perfetto
BACKGROUND AND AIM: Either 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA. METHODS AND RESULTS: We retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA...
May 23, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28536896/helical-distribution-of-hypertrophy-in-patients-with-hypertrophic-cardiomyopathy-prevalence-and-clinical-implications
#19
Dafne Viliani, Eduardo Pozo, Norma Aguirre, Alberto Cecconi, María J Olivera, Paloma Caballero, Luis J Jiménez-Borreguero, Fernando Alfonso
Recently a novel pattern of helical distribution of hypertrophy has been described in patients with hypertrophic cardiomyopathy (HCM). Our aim was to determine its prevalence and potential implications in an unselected cohort. One-hundred- and eight consecutive patients diagnosed with HCM by cardiac magnetic resonance (CMR) were included (median clinical follow up of 1718 days). All clinical and complementary test information was prospectively collected. The presence of a helical pattern was assessed by a simple measurement of the maximal left ventricle (LV) wall thickness (LVWT) for each of the 17 classical LV segments and it was classified in one of three types according to its extension...
May 23, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28536660/sorafenib-associated-heart-failure-complicated-by-cardiogenic-shock-after-treatment-of-advanced-stage-hepatocellular-carcinoma-a-clinical-case-discussion
#20
Candace Wu, Kamal Shemisa
Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI), targets multiple tyrosine kinase receptors (TKRs) involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC) presented with symptoms of decompensated heart failure...
2017: Case Reports in Cardiology
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