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Cardiac Contractility Modulation

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https://www.readbyqxmd.com/read/28510118/tampering-with-springs-phosphorylation-of-titin-affecting-the-mechanical-function-of-cardiomyocytes
#1
REVIEW
Nazha Hamdani, Melissa Herwig, Wolfgang A Linke
Reversible post-translational modifications of various cardiac proteins regulate the mechanical properties of the cardiomyocytes and thus modulate the contractile performance of the heart. The giant protein titin forms a continuous filament network in the sarcomeres of striated muscle cells, where it determines passive tension development and modulates active contraction. These mechanical properties of titin are altered through post-translational modifications, particularly phosphorylation. Titin contains hundreds of potential phosphorylation sites, the functional relevance of which is only beginning to emerge...
April 10, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28509888/cardiac-contractility-modulation-a-technical-guide-for-device-implantation
#2
Jürgen Kuschyk, Axel Kloppe, Stephan Schmidt-Schweda, Hendrik Bonnemeier, Benny Rousso, Susanne Röger
This article provides a technical description of common implant practice for delivery of cardiac contractility modulation (CCM) therapy to heart failure patients. As of September 2016, the authors of this article collectively have been involved with more than 400 system implantations in five medical centers, beginning with the advent of CCM therapy approximately 12 years ago. CCM therapy has been evaluated in a variety of studies, and was shown to be safe and effective and of benefit to patient quality of life and exercise capacity...
2017: Reviews in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28498888/cardiomyocyte-specific-loss-of-mitochondrial-p32-c1qbp-causes-cardiomyopathy-and-activates-stress-responses
#3
Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima, Dongchon Kang
Aims: Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. The goal of this study was to examine the physiological function of mitochondrial p32/C1qbp in the heart...
May 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28491808/cardiac-contractility-modulation-therapy-are-there-superresponders
#4
Bandar Al-Ghamdi, Azam Shafquat, Yaseen Mallawi
No abstract text is available yet for this article.
April 2017: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28485381/regulation-of-cardiomyocyte-behavior-in-zebrafish-trabeculation-by-neuregulin-2a-signaling
#5
S Javad Rasouli, Didier Y R Stainier
Trabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28450452/nanonet-force-microscopy-for-measuring-forces-in-single-smooth-muscle-cells-of-human-aorta
#6
Alexander Hall, Patrick Chan, Kevin Sheets, Matthew Apperson, Christopher Delaughter, Thomas G Gleason, Julie A Phillippi, Amrinder Nain
A number of innovative methods exist to measure cell-matrix adhesive forces, which have yet to accurately describe and quantify the intricate interplay of a cell and its fibrous extracellular matrix (ECM). In cardiovascular pathologies, such as aortic aneurysm, new knowledge on the involvement of cell-matrix forces could lead to elucidation of disease mechanisms. To better understand this dynamics we measured primary human aortic single smooth muscle cell (SMC) forces using nanonet force microscopy (NFM) in both inside-out (I-O intrinsic contractility) and outside-in (O-I external perturbation) modes...
April 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428008/force-development-and-intracellular-ca-2-in-intact-cardiac-muscles-from-gravin-mutant-mice
#7
Zhitao Li, Sonal Singh, Santosh V Suryavanshi, Wengang Ding, Xiaoxu Shen, Cori S Wijaya, Wei Dong Gao, Bradley K McConnell
Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2-adrenergic receptor (β2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca(2+) transient ([Ca(2+)]i) were measured...
April 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#8
Ahmed F El-Yazbi, Karim S Ibrahim, Hanan M El-Gowelli, Nevine M El-Deeb, Mahmoud M El-Mas
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction...
April 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28381504/insulin-receptor-substrate-signaling-controls-cardiac-energy-metabolism-and-heart-failure
#9
Cathy A Guo, Shaodong Guo
The heart is an insulin-dependent and energy consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth, and survival. Heart failure is highly associated with insulin resistance and heart failure patients suffer from the cardiac energy deficiency, structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics, and impairing cardiac contractility...
April 5, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28372809/the-role-of-stim1-and-soce-in-smooth-muscle-contractility
#10
REVIEW
C H Feldman, C A Grotegut, P B Rosenberg
Contraction is a central feature for skeletal, cardiac and smooth muscle; this unique feature is largely dependent on calcium (Ca(2+)) signaling and therefore maintenance of internal Ca(2+) stores. Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane protein that functions as a Ca(2+) sensor for the activation store-operated calcium channels (SOCCs) on the plasma membrane in response to depleted internal sarco(endo)plasmic (S/ER) reticulum Ca(2+) stores. STIM1 was initially characterized in non-excitable cells; however, evidence from both animal models and human mutations suggests a role for STIM1 in modulating Ca(2+) homeostasis in excitable tissues as well...
March 10, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28356163/a-novel-system-for-continuous-real-time-monitoring-of-heart-motion-signals
#11
Guy Dori, Jorge E Schliamser, Oscar Lichtenstein, Ilia Anshelevich, Moshe Y Flugelman
BACKGROUND: Understanding cardiac mechanics is important for developing cardiac therapies. Current modalities for assessing cardiac mechanics sample patient's heart at specific heart rate, contractility, preload, and afterload. The objective of this study was to test the feasibility of a novel system composed of intra-cardiac leads equipped with an inertial module chip (3D accelerometers and 3D gyroscopes) in monitoring continuous heart motion. METHODS: In this descriptive study, four healthy pigs were anesthetized and instrumented with motion-sensitive intra-cardiac leads; the temporal correlation between signals from motion sensors and tissue Doppler from the chest wall were studied; changes in real-time heart accelerations (ACC) and angular velocity (ANGV) were reported as percentages of change from baseline...
March 29, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28345052/cardiac-myosin-binding-protein-c-ser-302-phosphorylation-regulates-cardiac-%C3%AE-adrenergic-reserve
#12
Ranganath Mamidi, Kenneth S Gresham, Jiayang Li, Julian E Stelzer
Phosphorylation of cardiac myosin binding protein-C (MyBP-C) modulates cardiac contractile function; however, the specific roles of individual serines (Ser) within the M-domain that are targets for β-adrenergic signaling are not known. Recently, we demonstrated that significant accelerations in in vivo pressure development following β-agonist infusion can occur in transgenic (TG) mouse hearts expressing phospho-ablated Ser(282) (that is, TG(S282A)) but not in hearts expressing phospho-ablation of all three serines [that is, Ser(273), Ser(282), and Ser(302) (TG(3SA))], suggesting an important modulatory role for other Ser residues...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28343276/an-updated-review-of-cardiac-devices-in-heart-failure
#13
REVIEW
C Murphy, H Zafar, F Sharif
BACKGROUND: Heart failure has the highest rates of adult hospitalisations, the highest mortality rates and significant costs associated with its care. The cost of heart failure is expected continue to grow on a global scale, with $108 billion spent on heart failure in 2012. Mortality rates are high, with incident cases of heart failure resulting in 30% 1-year mortality, and in hospital mortality of acute heart failure, 28%. METHODS AND RESULTS: This article reviews the devices currently in use for the treatment of heart failure, as well as those that are under investigation...
March 25, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28333387/pathophysiological-fundamentals-of-diabetic-cardiomyopathy
#14
Xinyue Hu, Tao Bai, Zheng Xu, Qiuju Liu, Yang Zheng, Lu Cai
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28328746/cross-talk-between-insulin-signaling-and-gpcrs
#15
Qin Fu, Qian Shi, Toni M West, Yang K Xiang
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between two receptor signaling systems, and forming an integrated and dynamic network...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28322254/stk38-modulates-rbm24-protein-stability-to-regulate-sarcomere-assembly-in-cardiomyocytes
#16
Jing Liu, Xu Kong, Lee Yew Mun, Zhang Meng Kai, Guo Li Yan, Yu Lin, Teck Kwang Lim, Qingsong Lin, Xiu Qin Xu
RNA-binding protein Rbm24 is a key regulator of heart development and required for sarcomere assembly and heart contractility. Yet, its underlying mechanism remains unclear. Here, we link serine/threonine kinase 38 (Stk38) signaling to the regulation of Rbm24 by showing that Rbm24 phosphorylation and its function could be modulated by Stk38. Using co-immunoprecipitation coupled with mass spectrometry technique, we identified Stk38 as an endogenous binding partner of Rbm24. Stk38 knockdown resulted in decreased Rbm24 protein level in cardiomyocytes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275246/sarcoplasmic-reticulum-mitochondria-communication-in-cardiovascular-pathophysiology
#17
REVIEW
Camila Lopez-Crisosto, Christian Pennanen, Cesar Vasquez-Trincado, Pablo E Morales, Roberto Bravo-Sagua, Andrew F G Quest, Mario Chiong, Sergio Lavandero
Repetitive, calcium-mediated contractile activity renders cardiomyocytes critically dependent on a sustained energy supply and adequate calcium buffering, both of which are provided by mitochondria. Moreover, in vascular smooth muscle cells, mitochondrial metabolism modulates cell growth and proliferation, whereas cytosolic calcium levels regulate the arterial vascular tone. Physical and functional communication between mitochondria and sarco/endoplasmic reticulum and balanced mitochondrial dynamics seem to have a critical role for optimal calcium transfer to mitochondria, which is crucial in calcium homeostasis and mitochondrial metabolism in both types of muscle cells...
June 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28256297/insulin-and-%C3%AE-adrenergic-receptor-signaling-crosstalk-in-heart
#18
REVIEW
Qin Fu, Qingtong Wang, Yang K Xiang
Recent advances show that insulin may affect β adrenergic receptor (βAR) signaling in the heart to modulate cardiac function in clinically relevant states, such as diabetes mellitus (DM) and heart failure (HF). Conversely, activation of βAR regulates cardiac glucose uptake and promotes insulin resistance (IR) in HF. Here, we discuss the recent characterization of the interaction between the cardiac insulin receptor (InsR) and βAR in the myocardium, in which insulin stimulation crosstalks with cardiac βAR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of β2AR...
February 27, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28229200/-current-impact-of-cardiac-implantable-electronic-devices
#19
J Kuschyk, B Rudic, M Borggrefe, I Akin
Sudden cardiac death and chronic heart failure are among the main contributors to persisting high mortality rates in Germany. In addition to removal of causal factors and guideline-conform pharmacological therapy, therapy with cardiac implantable electronic devices (CIED) is of undisputed importance. Subcutaneous defibrillators have the advantage that they do not have intracardiac electrodes but still have the same efficacy and safety. For patients with a wide QRS complex and reduced ejection fraction, cardiac resynchronization has led to a reduction of morbidity and mortality...
February 22, 2017: Herz
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#20
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
February 20, 2017: Journal of Molecular and Cellular Cardiology
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