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https://www.readbyqxmd.com/read/27914945/effects-of-zacopride-a-moderate-ik1-channel-agonist-on-triggered-arrhythmia-and-contractility-in-human-ventricular-myocardium
#1
Mohammad T Elnakish, Benjamin D Canan, Ahmet Kilic, Peter J Mohler, Paul M L Janssen
Ventricular tachycardia is the leading cause of sudden arrhythmic death in the U.S. Recently, the moderate IK1 channel activator, zacopride, was shown to suppress triggered ventricular tachycardia in rats. Nonetheless, concerns were raised about the possibility of pro-arrhythmic activity after IK1 channel stimulation based on the promising anti-arrhythmic strategy of IK1 blockade in other animal models. Therefore, the goal of the current study was to investigate the ex-vivo effects of zacopride on triggered arrhythmia and contractility in ventricular human myocardium in order to validate data that was solely obtained from animal models...
November 30, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27907103/tbx20-is-an-essential-regulator-of-embryonic-heart-growth-in-zebrafish
#2
Steffen Just, Linda Raphel, Ina M Berger, Anja Bühler, Mirjam Keßler, Wolfgang Rottbauer
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein...
2016: PloS One
https://www.readbyqxmd.com/read/27906129/the-evolutionary-origin-of-bilaterian-smooth-and-striated-myocytes
#3
Thibaut Brunet, Antje Hl Fischer, Patrick Rh Steinmetz, Antonella Lauri, Paola Bertucci, Detlev Arendt
The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed, and nervous control...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#4
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27886226/functional-improvement-and-regression-of-medial-hypertrophy-in-the-remodeled-pulmonary-artery-after-correction-of-systemic-left-to-right-shunt
#5
Chih-Hsin Hsu, Jun-Neng Roan, Jyh-Hong Chen, Chen-Fuh Lam
The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884701/cardiac-inositol-1-4-5-trisphosphate-receptors
#6
REVIEW
M Iveth Garcia, Darren Boehning
Calcium is a second messenger that regulates almost all cellular functions. In cardiomyocytes, calcium plays an integral role in many functions including muscle contraction, gene expression, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) are a family of calcium channels that are ubiquitously expressed in all tissues. In the heart, IP3Rs have been associated with regulation of cardiomyocyte function in response to a variety of neurohormonal agonists, including those implicated in cardiac disease...
November 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27881552/cardiac-t-tubule-microanatomy-and-function
#7
REVIEW
TingTing Hong, Robin M Shaw
Unique to striated muscle cells, transverse tubules (t-tubules) are membrane organelles that consist of sarcolemma penetrating into the myocyte interior, forming a highly branched and interconnected network. Mature t-tubule networks are found in mammalian ventricular cardiomyocytes, with the transverse components of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain membrane microdomains enriched with ion channels and signaling molecules. The microdomains serve as key signaling hubs in regulation of cardiomyocyte function...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27867361/calcium-sensing-receptor-regulates-cytosolic-ca-2-and-plays-a-major-role-in-the-development-of-pulmonary-hypertension
#8
REVIEW
Kimberly A Smith, Ramon J Ayon, Haiyang Tang, Ayako Makino, Jason X-J Yuan
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary vascular resistance (PVR) leading to right heart failure and premature death. The increased PVR results in part from pulmonary vascular remodeling and sustained pulmonary vasoconstriction. Excessive pulmonary vascular remodeling stems from increased pulmonary arterial smooth muscle cell (PASMC) proliferation and decreased PASMC apoptosis. A rise in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) in PASMC is a major trigger for pulmonary vasoconstriction and a key stimulus for PASMC proliferation and migration, both contributing to the development of pulmonary vascular remodeling...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27860516/assessment-of-the-brainstem-mediated-stapedius-muscle-reflex-in-andean-children-living-at-high-altitudes
#9
S Allen Counter, Leo H Buchanan, Fernando Ortega, Anthony B Jacobs, Göran Laurell
Counter, S. Allen, Leo H. Buchanan, Fernando Ortega, Anthony B. Jacobs, and Göran Laurell. Assessment of the brainstem-mediated stapedius muscle reflex in Andean children living at high altitudes. High Alt Med Biol. 16:000-000, 2016.-This study examined the physiological thresholds, amplitude growth, and contraction duration of the acoustic stapedius reflex (ASR) in Andean children aged 2-17 years living at altitudes of 2850 m (Altitude I Group) and 3973 m (Altitude II Group) as part of a general medical assessment of the health status of the children...
November 18, 2016: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/27856252/the-interchain-disulfide-cross-linking-of-tropomyosin-alters-its-regulatory-properties-and-interaction-with-actin-filament
#10
Alexander M Matyushenko, Natalia V Artemova, Daniil V Shchepkin, Galina V Kopylova, Salavat R Nabiev, Larisa V Nikitina, Dmitrii I Levitsky, Sergey Y Bershitsky
Tropomyosin (Tpm) is an α-helical coiled-coil actin-binding protein that plays a key role in the Ca(2+)-regulated contraction of striated muscles. Two chains of Tpm can be cross-linked by formation of a disulfide bond between Cys-190 residues. Normally, the SH-groups of these residues in cardiac muscle are in reduced state but in heart pathologies the interchain cross-linking of Tpm was shown to occur. Previous studies have shown that this cross-linking increases the thermal stability of the C-terminal part of the Tpm molecule...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27853436/the-importance-of-intrinsically-disordered-segments-of-cardiac-troponin-in-modulating-function-by-phosphorylation-and-disease-causing-mutations
#11
REVIEW
Maria Papadaki, Steven B Marston
Troponin plays a central role in regulation of muscle contraction. It is the Ca(2+) switch of striated muscles including the heart and in the cardiac muscle it is physiologically modulated by PKA-dependent phosphorylation at Ser22 and 23. Many cardiomyopathy-related mutations affect Ca(2+) regulation and/or disrupt the relationship between Ca(2+) binding and phosphorylation. Unlike the mechanism of heart activation, the modulation of Ca(2+)-sensitivity by phosphorylation of the cardiac specific N-terminal segment of TnI (1-30) is structurally subtle and has proven hard to investigate...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27851958/alternative-splicing-of-four-trafficking-genes-regulates-myofiber-structure-and-skeletal-muscle-physiology
#12
Jimena Giudice, James A Loehr, George G Rodney, Thomas A Cooper
During development, transcriptional and post-transcriptional networks are coordinately regulated to drive organ maturation. Alternative splicing contributes by producing temporal-specific protein isoforms. We previously found that genes undergoing splicing transitions during mouse postnatal heart development are enriched for vesicular trafficking and membrane dynamics functions. Here, we show that adult trafficking isoforms are also expressed in adult skeletal muscle and hypothesize that striated muscle utilizes alternative splicing to generate specific isoforms required for function of adult tissue...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27833558/serelaxin-elicits-bronchodilation-and-enhances-%C3%AE-adrenoceptor-mediated-airway-relaxation
#13
Maggie Lam, Simon G Royce, Chantal Donovan, Maria Jelinic, Laura J Parry, Chrishan S Samuel, Jane E Bourke
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27825981/structures-reveal-details-of-small-molecule-binding-to-cardiac-troponin
#14
Fangze Cai, Monica X Li, Sandra E Pineda-Sanabria, Shorena Gelozia, Steffen Lindert, Frederick West, Brian D Sykes, Peter M Hwang
In cardiac and skeletal muscle, the troponin complex turns muscle contraction on and off in a calcium-dependent manner. Many small molecules are known to bind to the troponin complex to modulate its calcium binding affinity, and this may be useful in a broad range of conditions in which striated muscle function is compromised, such as congestive heart failure. As a tool for developing drugs specific for the cardiac isoform of troponin, we have designed a chimeric construct (cChimera) consisting of the regulatory N-terminal domain of cardiac troponin C (cNTnC) fused to the switch region of cardiac troponin I (cTnI), mimicking the key binding event that turns on muscle contraction...
November 5, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27819072/apoptosis-based-therapy-to-treat-pulmonary-arterial-hypertension
#15
Yuichiro J Suzuki, Yasmine F Ibrahim, Nataliia V Shults
Pulmonary arterial hypertension (PAH) is rare, but patients who are diagnosed with this disease still suffer from a lack of satisfactory treatment strategies to prolong survival. While currently approved drugs for PAH have some benefits, these vasodilators only have limited efficacy for eliminating pulmonary vascular remodeling and reducing mortality. Thus, our laboratory has been exploring the use of aggressive drugs, which are capable of causing apoptotic cell death, to treat PAH. We have so far found that three classes of anti-tumor agents, including anthracyclines, taxanes, and proteasome inhibitors, are capable of reducing pulmonary vascular thickness in rats with PAH...
2016: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/27818306/i-wire-heart-on-a-chip-ii-biomechanical-analysis-of-contractile-three-dimensional-cardiomyocyte-tissue-constructs
#16
Alison K Schroer, Matthew S Shotwell, Veniamin Y Sidorov, John P Wikswo, W David Merryman
This companion study presents the biomechanical analysis of the "I-Wire" platform using a modified Hill model of muscle mechanics that allows for further characterization of construct function and response to perturbation. The I-Wire engineered cardiac tissue construct (ECTC) is a novel experimental platform to investigate cardiac cell mechanics during auxotonic contraction. Whereas passive biomaterials often exhibit nonlinear and dissipative behavior, active tissue equivalents, such as ECTCs, also expend metabolic energy to perform mechanical work that presents additional challenges in quantifying their properties...
November 3, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27807201/molecular-pathophysiology-of-congenital-long-qt-syndrome
#17
REVIEW
M S Bohnen, G Peng, S H Robey, C Terrenoire, V Iyer, K J Sampson, R S Kass
Ion channels represent the molecular entities that give rise to the cardiac action potential, the fundamental cellular electrical event in the heart. The concerted function of these channels leads to normal cyclical excitation and resultant contraction of cardiac muscle. Research into cardiac ion channel regulation and mutations that underlie disease pathogenesis has greatly enhanced our knowledge of the causes and clinical management of cardiac arrhythmia. Here we review the molecular determinants, pathogenesis, and pharmacology of congenital Long QT Syndrome...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27789769/effect-of-sodium-nitrite-on-local-control-of-contracting-skeletal-muscle-microvascular-oxygen-pressure-in-healthy-rats
#18
Trenton D Colburn, Scott K Ferguson, Clark T Holdsworth, Jesse C Craig, Timothy I Musch, David C Poole
Exercise intolerance characteristic of diseases such as chronic heart failure (CHF) and diabetes is associated with reduced nitric oxide (NO) bioavailability from nitric oxide synthase (NOS), resulting in an impaired microvascular O2 driving pressure (PO2mv; O2 delivery / O2 utilization) and metabolic control. Infusions of the potent NO donor sodium nitroprusside augment NO bioavailability, yet decrease mean arterial pressure (MAP) thereby reducing its potential efficacy for patient populations. To eliminate or reduce hypotensive sequelae, NO2(-) was superfused onto the spinotrapezius muscle...
October 27, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27754186/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#19
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27743468/a-monolithic-3d-0d-coupled-closed-loop-model-of-the-heart-and-the-vascular-system-experiment-based-parameter-estimation-for-patient-specific-cardiac-mechanics
#20
M Hirschvogel, M Bassilious, L Jagschies, S M Wildhirt, M W Gee
A model for patient-specific cardiac mechanics simulation is introduced, incorporating a 3-dimensional finite element model of the ventricular part of the heart which is coupled to a reduced-order 0-dimensional closed-loop vascular system, heart valve and atrial chamber model.The ventricles are modeled by a nonlinear orthotropic passive material law. The electrical activation is mimicked by a prescribed parametrized active stress acting along a generic muscle fiber orientation. Our activation function is constructed such that the start of ventricular contraction and relaxation as well as the active stress curve's slope are parameterized...
October 15, 2016: International Journal for Numerical Methods in Biomedical Engineering
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