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Cardiac development, cardiac remodelling, cardiac function

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https://www.readbyqxmd.com/read/28542428/age-dependent-electrical-and-morphological-remodeling-of-the-drosophila-heart-caused-by-herg-seizure-mutations
#1
Karen Ocorr, Alexander Zambon, Yoav Nudell, Santiago Pineda, Soda Diop, Min Tang, Takeshi Akasaka, Erika Taylor
Understanding the cellular-molecular substrates of heart disease is key to the development of cardiac specific therapies and to the prevention of off-target effects by non-cardiac targeted drugs. One of the primary targets for therapeutic intervention has been the human ether a go-go (hERG) K+ channel that, together with the KCNQ channel, controls the rate and efficiency of repolarization in human myocardial cells. Neither of these channels plays a major role in adult mouse heart function; however, we show here that the hERG homolog seizure (sei), along with KCNQ, both contribute significantly to adult heart function as they do in humans...
May 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28533209/rationale-and-design-of-a-clinical-trial-to-evaluate-the-safety-and-efficacy-of-intracoronary-infusion-of-allogeneic-human-cardiac-stem-cells-in-patients-with-acute-myocardial-infarction-and-left-ventricular-dysfunction-the-randomized-multicenter-double-blind
#2
Ricardo Sanz-Ruiz, Ana Casado Plasencia, Luis R Borlado, María Eugenia Fernández-Santos, Reem Al-Daccak, Piet Claus, Itziar Palacios, Rafael Sádaba, Dominique Charron, Jan Bogaert, Miguel Mulet, Raquel Yotti, Inmaculada Gilaberte, Antonio Bernad, Javier Bermejo, Stefan Janssens, Francisco Fernández-Avilés
Rationale: Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure (HF). The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction (AMI) with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and "first-generation" stem cells have yielded inconsistent benefits and mixed results...
May 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28528661/right-sided-cardiac-dysfunction-in-heart-failure-with-preserved-ejection-fraction-and-worsening-renal-function
#3
Monica Mukherjee, Kavita Sharma, Jose A Madrazo, Ryan J Tedford, Stuart D Russell, Allison G Hays
In urban populations, worsening renal function (WRF) is well established in patients hospitalized with acute decompensated heart failure with preserved ejection fraction (HFpEF). However, the mechanisms for development of WRF in the setting of acute HF in HFpEF are unclear. In the present study, we sought to characterize conventional echocardiographic measures of right ventricular (RV) chamber size and function to determine whether RV dysfunction and/or adverse RV remodeling is related to WRF in patients with HFpEF...
April 27, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28522833/parkin-regulation-of-chop-modulates-susceptibility-to-cardiac-endoplasmic-reticulum-stress
#4
Kim Han, Shahin Hassanzadeh, Komudi Singh, Sara Menazza, Tiffany T Nguyen, Mark V Stevens, An Nguyen, Hong San, Stasia A Anderson, Yongshun Lin, Jizhong Zou, Elizabeth Murphy, Michael N Sack
The regulatory control of cardiac endoplasmic reticulum (ER) stress is incompletely characterized. As ER stress signaling upregulates the E3-ubiquitin ligase Parkin, we investigated the role of Parkin in cardiac ER stress. Parkin knockout mice exposed to aortic constriction-induced cardiac pressure-overload or in response to systemic tunicamycin (TM) developed adverse ventricular remodeling with excessive levels of the ER regulatory C/EBP homologous protein CHOP. CHOP was identified as a Parkin substrate and its turnover was Parkin-dose and proteasome-dependent...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512310/fgf23-fgfr4-mediated-left-ventricular-hypertrophy-is-reversible
#5
Alexander Grabner, Karla Schramm, Neerupma Silswal, Matt Hendrix, Christopher Yanucil, Brian Czaya, Saurav Singh, Myles Wolf, Sven Hermann, Jörg Stypmann, Giovana Seno Di Marco, Marcus Brand, Michael J Wacker, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512159/employing-extracellular-volume-cardiovascular-magnetic-resonance-measures-of-myocardial-fibrosis-to-foster-novel-therapeutics
#6
Erik B Schelbert, Hani N Sabbah, Javed Butler, Mihai Gheorghiade
Quantifying myocardial fibrosis (MF) with myocardial extracellular volume measures acquired during cardiovascular magnetic resonance promises to transform clinical care by advancing pathophysiologic understanding and fostering novel therapeutics. Extracellular volume quantifies MF by measuring the extracellular compartment depicted by the myocardial uptake of contrast relative to plasma. MF is a key domain of dysfunctional but viable myocardium among others (eg, microvascular dysfunction and cardiomyocyte/mitochondrial dysfunction)...
June 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28502095/the-impact-of-age-and-frailty-on-ventricular-structure-and-function-in-c57bl-6j-mice
#7
H A Feridooni, A E Kane, O Ayaz, A Boroumandi, N Polidovitch, R G Tsushima, R A Rose, S E Howlett
KEY POINTS: Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals. That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a 'frailty index'. We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction...
May 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28498548/engineered-3d-cardiac-fibrotic-tissue-to-study-fibrotic-remodeling
#8
Amir Hossein Sadeghi, Su Ryon Shin, Janine C Deddens, Giuseppe Fratta, Serena Mandla, Iman K Yazdi, Gyan Prakash, Silvia Antona, Danilo Demarchi, Marc P Buijsrogge, Joost P G Sluijter, Jesper Hjortnaes, Ali Khademhosseini
Activation of cardiac fibroblasts into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of cardiac fibroblasts when cultured on two-dimensional (2D) culture plates. In this study, a simplified three-dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor-β1 (TGF-β1), is presented to recapitulate a fibrogenic microenvironment. It is hypothesized that the quiescent state of cardiac fibroblasts can be maintained by mimicking the mechanical stiffness of native heart tissue...
May 12, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28472473/fgf21-is-required-for-cardiac-remodeling-in-pregnancy
#9
I Redondo-Angulo, A Mas-Stachurska, M Sitges, F J Tinahones, M Giralt, F Villarroya, A Planavila
Aims—: Fibroblast growth factor-21 (Fgf21) is an endocrine factor that contributes to many physiological and pathological processes, mainly via its action as a metabolic regulator. Recent studies have shown that Fgf21 plays an important role in cardiac tissue. Pregnancy offers a physiological model of adaptive and reversible heart enlargement, but the molecular mechanisms underlying this cardiac hypertrophy are poorly understood. Therefore, the aim was to analyze the role of Fgf21 during late pregnancy, and assess the physiological relevance of Fgf21 for cardiac tissue during this process...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28471759/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#10
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 29, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28455288/cardiac-myofibrillar-contractile-properties-during-the-progression-from-hypertension-to-decompensated-heart-failure
#11
Laurin M Hanft, Craig A Emter, Kerry S McDonald
Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, calcium handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of this study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure we predicted marked depression in these contractile properties...
April 28, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28455218/age-dependent-functional-crosstalk-between-cardiac-fibroblasts-and-cardiomyocytes-in-a-3d-engineered-cardiac-tissue
#12
Yanzhen Li, Huda Asfour, Nenad Bursac
Complex heterocellular interactions between cardiomyocytes and fibroblasts in the heart involve their bidirectional signaling via cell-cell contacts, paracrine factors, and extracellular matrix (ECM). These interactions vary with heart development and pathology leading to changes in cardiac structure and function. Whether cardiac fibroblasts of different ages interact differentially with cardiomyocytes to distinctly impact their function remains unknown. Here, we explored the direct structural and functional effects of fetal and adult cardiac fibroblasts on cardiomyocytes using a tissue-engineered 3D co-culture system...
April 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28439652/myocardial-extracellular-volume-fraction-quantified-by-cardiovascular-magnetic-resonance-is-increased-in-hypertension-and-associated-with-left-ventricular-remodeling
#13
Shuli Wang, Hongjie Hu, Minjie Lu, Arlene Sirajuddin, Jinghui Li, Jing An, Xiuyu Chen, Gang Yin, Tian Lan, Linlin Dai, Yan Zhang, Xiaorong Yin, Lei Song, Aimin Dang, Peter Kellman, Andrew E Arai, Shihua Zhao
OBJECTIVES: To determine whether extracellular volume fraction (ECV) quantification by cardiac magnetic resonance (CMR) can demonstrate left ventricle (LV) abnormalities and relationship between ECV and LV remodeling in hypertension (HTN) patients METHODS: ECV quantification was prospectively performed in 134 consecutive HTN patients and 97 healthy subjects. Individual and regional ECV were compared to the regions on late gadolinium enhancement (LGE) images. Statistical analysis of the relationship between LV global functional parameters and ECV was carried out using Pearson's correlation, Student's t test and multiple regressions...
April 24, 2017: European Radiology
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#14
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28436080/genotype-specific-pathogenic-effects-in-human-dilated-cardiomyopathy
#15
Ilse Ae Bollen, Maike Schuldt, Magdalena Harakalova, Aryan Vink, Folkert W Asselbergs, Jose R Pinto, Martina Krüger, Diederik Wd Kuster, Jolanda van der Velden
BACKGROUND: Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation ) and cardiac troponin T (TNNT2p.K217deletion ; also known as the K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q ). METHODS: We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue...
April 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#16
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016, in Bethesda, Maryland, to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
May 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28432058/mk5-haplodefficiency-attenuates-hypertrophy-and-preserves-diastolic-function-during-remodeling-induced-by-chronic-pressure-overload-in-the-mouse-heart
#17
Sherin Nawaito, Dharmendra Dingar, Pramod Sahadevan, Bahira Hussein, Fatiha Sahmi, Yanfen Shi, Marc-Antoine Gillis, Matthias Gaestel, Jean-Claude Tardif, Bruce G Allen
MK5 is a protein serine and threonine kinase that is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological function(s) of MK5 remain unknown. Herein we examine the effect of MK5 haplodeficiency on cardiac function and myocardial remodeling. At 12-weeks of age, MK5 haplodeficient mice (MK5(+/-)) were smaller than age-matched wild-type litter mates (MK5(+/+)), with similar diastolic function but reduced systolic function. Transverse aortic constriction (TAC) was employed to induce a chronic pressure overload in twelve-week-old male MK5(+/-) and MK5(+/+) mice...
April 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28430919/non-coding-rnas-in-cardiovascular-diseases-diagnostic-and-therapeutic-perspectives
#18
Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28423119/importance-of-serca2a-on-early-isolated-diastolic-dysfunction-induced-by-supravalvular-aortic-stenosis-in-rats
#19
C F S M P Silveira, D H S Campos, P P Freire, A F Deus, K Okoshi, C R Padovani, A C Cicogna
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively...
April 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28421204/diabetic-cardiomyopathy-current-approach-and-potential-diagnostic-and-therapeutic-targets
#20
REVIEW
Georgiana-Emmanuela Gilca, Gabriela Stefanescu, Oana Badulescu, Daniela-Maria Tanase, Iris Bararu, Manuela Ciocoiu
Although ischemic heart disease is the major cause of death in diabetic patients, diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant entity. Considering that it comprises a variety of mechanisms and effects on cardiac function, increasing the risk of heart failure and worsening the prognosis of this patient category, DCM represents an important complication of diabetes mellitus, with a silent development in its earlier stages, involving intricate pathophysiological mechanisms, including oxidative stress, defective calcium handling, altered mitochondrial function, remodeling of the extracellular matrix, and consequent deficient cardiomyocyte contractility...
2017: Journal of Diabetes Research
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