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Cardiac Contractility Modulation

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https://www.readbyqxmd.com/read/29131758/titin-gene-and-protein-functions-in-passive-and-active-muscle
#1
Wolfgang A Linke
The thin and thick filaments of muscle sarcomeres are interconnected by the giant protein titin, which is a scaffolding filament, signaling platform, and provider of passive tension and elasticity in myocytes. This review summarizes recent insight into the mechanisms behind how titin gene mutations cause hereditary cardiomyopathy and how titin protein is mechanically active in skeletal and cardiac myocytes. A main theme is the evolving role of titin as a modulator of contraction. Topics include strain-sensing via titin in the sarcomeric A-band as the basis for length-dependent activation, titin elastic recoil and refolding of titin domains as an energy source, and Ca(2+)-dependent stiffening of titin stretched during eccentric muscle contractions...
November 13, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29120956/protein-kinase-c%C3%AE-deletion-causes-hypotension-and-decreased-vascular-contractility
#2
Brandi M Wynne, Cameron G McCarthy, Theodora Szasz, Patrick A Molina, Arlene B Chapman, R Clinton Webb, Janet D Klein, Robert S Hoover
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated...
November 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29117223/sensitivity-analysis-revealing-the-effect-of-modulating-ionic-mechanisms-on-calcium-dynamics-in-simulated-human-heart-failure
#3
Maria T Mora, Jose M Ferrero, Lucia Romero, Beatriz Trenor
Abnormal intracellular Ca2+ handling is the major contributor to the depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both the action potential and the Ca2+ dynamics, leading to a defective excitation-contraction coupling that ends in mechanical dysfunction. The importance of maintaining a correct intracellular Ca2+ concentration requires a better understanding of its regulation by ionic mechanisms. To study the electrical activity and ionic homeostasis of failing myocytes, a modified version of the O'Hara et al...
2017: PloS One
https://www.readbyqxmd.com/read/29052230/omecamtiv-mercabil-and-blebbistatin-modulate-cardiac-contractility-by-perturbing-the-regulatory-state-of-the-myosin-filament
#4
Thomas Kampourakis, Xuemeng Zhang, Yin-Biao Sun, Malcolm Irving
Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood...
October 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29018938/heart-failure-with-preserved-ejection-fraction-current-management-and-future-strategies-expert-opinion-on-the-behalf-of-the-nucleus-of-the-heart-failure-working-group-of-the-german-society-of-cardiology-dkg
#5
REVIEW
Carsten Tschöpe, Christoph Birner, Michael Böhm, Oliver Bruder, Stefan Frantz, Andreas Luchner, Lars Maier, Stefan Störk, Behrouz Kherad, Ulrich Laufs
About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities...
October 10, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29018025/peptidyl-prolyl-isomerase-1-regulates-ca-2-handling-by-modulating-sarco-endo-plasmic-reticulum-calcium-atpase-and-na-2-ca-2-exchanger-1-protein-levels-and-function
#6
Veronica Sacchi, Bingyan J Wang, Dieter Kubli, Alexander S Martinez, Jung-Kang Jin, Roberto Alvarez, Nirmala Hariharan, Christopher Glembotski, Takafumi Uchida, James S Malter, Yijun Yang, Polina Gross, Chen Zhang, Steven Houser, Marcello Rota, Mark A Sussman
BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored...
October 10, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28976521/cardiac-microphysiological-devices-with-flexible-thin-film-sensors-for-higher-throughput-drug-screening
#7
Johan U Lind, Moran Yadid, Ian Perkins, Blakely B O'Connor, Feyisayo Eweje, Christophe O Chantre, Matthew A Hemphill, Hongyan Yuan, Patrick H Campbell, Joost J Vlassak, Kevin K Parker
Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition strategies must be introduced. To this end, we here present an instrumented 24-well plate platform for higher-throughput studies of engineered human stem cell-derived cardiac muscle tissues that recapitulate the laminar structure of the native ventricle...
October 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28966144/effects-of-exercise-training-on-excitation-contraction-coupling-calcium-dynamics-and-protein-expression-in-the-heart-of-the-neotropical-fish-brycon-amazonicus
#8
Rafael Zanelli Rissoli, Eliton da Silva Vasconcelos, Francisco Tadeu Rantin, Ana Lúcia Kalinin
Matrinxã (Brycon amazonicus) is a great swimming performance teleost fish from the Amazon basin. However, the possible cardiac adaptations of this ability are still unknown. Therefore, the aim of the present work was to investigate the effects of prolonged exercise (EX group - 60days under 0.4BL·s(-1)) on ventricular contractility by (i) in-vitro analysis of contractility comparing the relative roles of sodium/calcium exchanger (NCX) and sarcoplasmic reticulum (SR) in the excitation-contraction (E-C) coupling and (ii) molecular analysis of NCX, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) and phospholamban (PLB) expression and quantification...
September 29, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28965207/phoenixin-14-detection-and-novel-physiological-implications-in-cardiac-modulation-and-cardioprotection
#9
C Rocca, F Scavello, M C Granieri, T Pasqua, N Amodio, S Imbrogno, A Gattuso, R Mazza, Maria Carmela Cerra, Tommaso Angelone
Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood-brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R)...
September 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#10
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28888956/oxysterol-5%C3%AE-cholestan-3-one-modulates-a-contractile-response-to-%C3%AE-2-adrenoceptor-stimulation-in-the-mouse-atria-involvement-of-no-signaling
#11
Vaycheslav I Sytchev, Yulia G Odnoshivkina, Roman V Ursan, Alexey M Petrov
AIM: Atrial β2-adrenoceptors provide an important mechanism for regulation of cardiac function and changes in their downstream signaling are involved in processes underlying heart disorders. We have investigated the mechanism by which the cholesterol metabolite 5α-cholestan-3-one (5ɑCh3) modulates inotropic effect of β2-adrenoceptor agonist fenoterol. MAIN METHODS: Atria from mice were electrically stimulated and changes in contraction amplitude in response to fenoterol were studied in 5ɑCh3-pretreated samples...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28886529/peroxisome-proliferator-activated-receptors-as-therapeutic-targets-for-heart-failure
#12
REVIEW
Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Eshak I Bahbah, Ahmed Elmaraezy, Aya Ashraf Ali, Asmaa Ashraf, Mohamed M Abdel-Daim
Heart failure (HF) is a common clinical syndrome that affects more than 23 million individuals worldwide. Despite the marked advances in its management, the mortality rates in HF patients have remained unacceptably high. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription regulators, involved in the regulation of fatty acid and glucose metabolism. PPAR agonists are currently used for the treatment of type II diabetes mellitus and hyperlipidemia; however, their role as therapeutic agents for HF remains under investigation...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28860469/prolonged-at1r-activation-induces-cav1-2-channel-internalization-in-rat-cardiomyocytes
#13
Tamara Hermosilla, Matías Encina, Danna Morales, Cristian Moreno, Carolina Conejeros, Hilda M Alfaro-Valdés, Felipe Lagos-Meza, Felipe Simon, Christophe Altier, Diego Varela
The cardiac L-type calcium channel is a multi-subunit complex that requires co-assembling of the pore-forming subunit CaV1.2 with auxiliary subunits CaVα2δ and CaVβ. Its traffic has been shown to be controlled by these subunits and by the activation of various G-protein coupled receptors (GPCR). Here, we explore the consequences of the prolonged activation of angiotensin receptor type 1 (AT1R) over CaV1.2 channel trafficking. Bioluminescence Resonance Energy Transfer (BRET) assay between β-arrestin and L-type channels in angiotensin II-stimulated cells was used to assess the functional consequence of AT1R activation, while immunofluorescence of adult rat cardiomyocytes revealed the effects of GPCR activation on CaV1...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859848/chronic-in-vivo-nitric-oxide-deficiency-impairs-cardiac-functional-recovery-after-ischemia-in-female-but-not-male-mice
#14
Laura A Bienvenu, James Morgan, Melissa E Reichelt, Lea M D Delbridge, Morag J Young
Nitric oxide (NO) is an important regulator of cardiac function and plays a key role in ischemic cardioprotection. The role of chronic NO deficiency in coordinating ischemic vulnerability in female myocardium has not been established. The aim of this study was to determine the influence of chronic in vivo NO synthase inhibition in modulating ex vivo ischemia-reperfusion responses in female hearts (relative to males). Mice were subjected to l-NAME (l-N(G)-Nitroarginine-methyl-ester) treatment in vivo for 8weeks...
August 30, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28842439/hypertrophic-cardiomyopathy-mutation-in-cardiac-troponin-t-r95h-attenuates-length-dependent-activation-in-guinea-pig-cardiac-muscle-fibers
#15
Alexis V Mickelson, Murali Chandra
The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated crossbridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect crossbridge recruitment dynamics to alter myofilament Ca(2+) sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if the hypertrophic cardiomyopathy-linked mutaton (TnTR94H)-induced effects on contractile function would be differently modulated by sarcomere length (SL)...
August 25, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28826719/advanced-glycation-end-products-receptor-rage-controls-myocardial-dysfunction-and-oxidative-stress-in-high-fat-fed-mice-by-sustaining-mitochondrial-dynamics-and-autophagy-lysosome-pathway
#16
Yichi Yu, Lei Wang, Florian Delguste, Arthur Durand, Axel Guilbaud, Clementine Rousselin, Ann Marie Schmidt, Frédéric Tessier, Eric Boulanger, Remi Neviere
Oxidative stress and mitochondrial dysfunction are recognized as major contributors of cardiovascular damage in diabetes and high fat diet (HFD) fed mice. Blockade of receptor for advanced glycation end products (RAGE) attenuates vascular oxidative stress and development of atherosclerosis. We tested whether HFD-induced myocardial dysfunction would be reversed in RAGE deficiency mice, in association with changes in oxidative stress damage, mitochondrial respiration, mitochondrial fission and autophagy-lysosomal pathway...
August 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28807827/the-endotoxemia-cardiac-dysfunction-is-attenuated-by-ampk-mtor-signaling-pathway-regulating-autophagy
#17
Jie Zhang, Peng Zhao, Nanhu Quan, Lin Wang, Xu Chen, Courtney Cates, Thomas Rousselle, Ji Li
AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK in lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway regulating autophagy in young and aged mice...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807153/c1q-tumor-necrosis-factor-related-protein-3-enhances-the-contractility-of-cardiomyocyte-by-increasing-calcium-sensitivity
#18
Cheng-Lin Zhang, Zheng-Ju Chen, Han Feng, Qian Zhao, Yang-Po Cao, Li Li, Jin-Yu Wang, Yan Zhang, Li-Ling Wu
C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that protects against myocardial infarction-induced cardiac dysfunction through its pro-angiogenic, anti-apoptotic, and anti-fibrotic effects. However, whether CTRP3 can directly affect the systolic and diastolic function of cardiomyocytes remains unknown. Adult rat cardiomyocytes were isolated and loaded with Fura-2AM. The contraction and Ca(2+) transient data was collected and analyzed by IonOptix system. 1 and 2μg/ml CTRP3 significantly increased the contraction of cardiomyocytes...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28792844/trpa1-ion-channel-stimulation-enhances-cardiomyocyte-contractile-function-via-a-camkii-dependent-pathway
#19
Spencer R Andrei, Monica Ghosh, Pritam Sinharoy, Souvik Dey, Ian N Bratz, Derek S Damron
RATIONALE: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored. OBJECTIVE: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action...
August 9, 2017: Channels
https://www.readbyqxmd.com/read/28747938/computed-tomography-angiography-for-imaging-results-of-neochordal-mitral-valve-repair
#20
Radosław Zwoliński, Anna Marcinkiewicz, Konrad Szymczyk, Jarosław Drożdż, Ryszard Jaszewski, Bogdan Jegier
INTRODUCTION: Degenerative mitral regurgitation is currently the most frequent indication for mitral valve repair. AIM: To visualize and assess the mid-term results of mitral valve repair with neochordae implantation, using computed tomography angiography (CTA) imaging. MATERIAL AND METHODS: The CTA with ECG gating and without modulation was applied in 10 patients to assess the results of a mitral valve sparing procedure. The results of 3 patients are presented...
June 2017: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
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