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Cardiac Contractility Modulation

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https://www.readbyqxmd.com/read/29301861/molecular-determinants-of-ph-regulation-in-the-cardiac-na-ca2-exchanger
#1
Scott John, Brian Kim, Riccardo Olcese, Joshua I Goldhaber, Michela Ottolia
The cardiac Na+-Ca2+ exchanger (NCX) plays a critical role in the heart by extruding Ca2+ after each contraction and thus regulates cardiac contractility. The activity of NCX is strongly inhibited by cytosolic protons, which suggests that intracellular acidification will have important effects on heart contractility. However, the mechanisms underlying this inhibition remain elusive. It has been suggested that pH regulation originates from the competitive binding of protons to two Ca2+-binding domains within the large cytoplasmic loop of NCX and requires inactivation by intracellular Na+ to fully develop...
January 4, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29301848/physiologic-pathologic-and-therapeutic-paracrine-modulation-of-cardiac-excitation-contraction-coupling
#2
REVIEW
Joshua Mayourian, Delaine K Ceholski, David M Gonzalez, Timothy J Cashman, Susmita Sahoo, Roger J Hajjar, Kevin D Costa
Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular trafficking, and subsequent sarcomere shortening and myofibrillar contraction. Neurohumoral β-adrenergic signaling is a well-established mediator of ECC; other signaling mechanisms, such as paracrine signaling, have also demonstrated significant impact on ECC but are less well understood. For example, resident heart endothelial cells are well-known physiological paracrine modulators of cardiac myocyte ECC mainly via NO and endothelin-1...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29279317/ak098656-a-novel-vascular-smooth-muscle-cell-dominant-long-noncoding-rna-promotes-hypertension
#3
Ling Jin, Xianjuan Lin, Lei Yang, Xiaofang Fan, Wenjie Wang, Shuangyue Li, Jing Li, Xiaoyan Liu, Minghui Bao, Xiao Cui, Jichun Yang, Qinghua Cui, Bin Geng, Jun Cai
Recent studies reported some long noncoding RNAs (lncRNAs)-mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs...
December 26, 2017: Hypertension
https://www.readbyqxmd.com/read/29273902/ampk-dependent-nitric-oxide-release-provides-contractile-support-during-hyperosmotic-stress
#4
Malena Morell, Juan Ignacio Burgos, Luis Alberto Gonano, Martin Vila Petroff
In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm)...
December 22, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29249433/does-presence-of-left-ventricular-contractile-reserve-improve-response-to-cardiac-resynchronization-therapy-an-updated-meta-analysis
#5
Nikolaos Papageorgiou, Rui Providência, Pier D Lambiase, Dimitris Tousoulis, Guy Lloyd, Sanjeev Bhattacharyya
BACKGROUND: Up to a third of patients undergoing cardiac resynchronization therapy (CRT) do not have a clinical or echocardiographic response. It is also unclear, whether contractile reserve (CR) could predict CRT response. This meta-analysis examines whether the presence of CR improves response to CRT and whether this is modulated by other clinical factors. METHODS: Search of PubMed/EMBASE/Cochrane databases for articles examining response to CRT stratified by the presence or not of CR...
February 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29239839/the-formin-diaph1-is-a-key-modulator-of-myocardial-ischemia-reperfusion-injury
#6
Karen M O'Shea, Radha Ananthakrishnan, Qing Li, Nosirudeen Quadri, Devi Thiagarajan, Gopalkrishna Sreejit, Lingjie Wang, Hylde Zirpoli, Juan Francisco Aranda, Arthur S Alberts, Ann Marie Schmidt, Ravichandran Ramasamy
The biochemical, ionic, and signaling changes that occur within cardiomyocytes subjected to ischemia are exacerbated by reperfusion; however, the precise mechanisms mediating myocardial ischemia/reperfusion (I/R) injury have not been fully elucidated. The receptor for advanced glycation end-products (RAGE) regulates the cellular response to cardiac tissue damage in I/R, an effect potentially mediated by the binding of the RAGE cytoplasmic domain to the diaphanous-related formin, DIAPH1. The aim of this study was to investigate the role of DIAPH1 in the physiological response to experimental myocardial I/R in mice...
November 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29198129/hemodynamic-effects-of-epinephrine-in-rats-evaluation-by-impedance-cardiography
#7
C H Turkseven, E Pekoglu, B Buyukakilli
BACKGROUND AND OBJECTIVES: This study was aimed to examine how inotropic effects of intravenously injected epinephrine change thoracic impedance measurements and to reveal the possible effects of this change on other hemodynamic parameters by using the technique of impedance cardiography. METHODS: 10 male Wistar Albino rats were divided into two equal groups: control and epinephrine. 0.2 mg/kg of epinephrine was administered to the rats in the epinephrine group via the tail vein...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29183906/cardiac-enriched-baf-chromatin-remodeling-complex-subunit-baf60c-regulates-gene-expression-programs-essential-for-heart-development-and-function
#8
Xin Sun, Swetansu K Hota, Yu-Qing Zhou, Stefanie Novak, Dario Miguel-Perez, Danos Christodoulou, Christine E Seidman, J G Seidman, Carol C Gregorio, R Mark Henkelman, Janet Rossant, Benoit G Bruneau
How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function...
November 28, 2017: Biology Open
https://www.readbyqxmd.com/read/29179177/permanently-hypoxic-cell-culture-yields-rat-bone-marrow-mesenchymal-cells-with-higher-therapeutic-potential-in-the-treatment-of-chronic-myocardial-infarction
#9
Yihua Liu, Xiaoxi Yang, Pablo Maureira, Aude Falanga, Vanessa Marie, Guillaume Gauchotte, Sylvain Poussier, Frederique Groubatch, Pierre-Yves Marie, Nguyen Tran
BACKGROUND: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29158260/the-actin-organizing-formin-protein-fhod3-is-required-for-postnatal-development-and-functional-maintenance-of-the-adult-heart-in-mice
#10
Tomoki Ushijima, Noriko Fujimoto, Sho Matsuyama, Meikun Kan-O, Hiroshi Kiyonari, Go Shioi, Yohko Kage, Sho Yamasaki, Ryu Takeya, Hideki Sumimoto
Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that directs formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here, we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29131758/titin-gene-and-protein-functions-in-passive-and-active-muscle
#11
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 Ca2+-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
#12
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
#13
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
#14
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
#15
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...
January 2018: 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
#16
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
#17
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
#18
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
#19
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
#20
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...
December 2017: Free Radical Biology & Medicine
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