Article
Cardiac & Cardiovascular Systems
Mingke Ni, Yanhui Li, Jinhong Wei, Zhenpeng Song, Hui Wang, Jinjing Yao, Yong-Xiang Chen, Darrell Belke, John Paul Estillore, Ruiwu Wang, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, Wei Feng, Ju Chen, Thomas M. M. Roston, Shubhayan Sanatani, Anna Lehman, S. R. Wayne Chen
Summary: A loss-of-function RyR2-I4855M(+/-) mutation is associated with left ventricular noncompaction (LVNC), which is characterized by increased Ca2+ release and elevated end-diastolic Ca2+ levels. This mutation may contribute to the development of RyR2-associated LVNC.
CIRCULATION RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Matthew J. Wleklinski, Dmytro O. Kryshtal, Kyungsoo Kim, Shan S. Parikh, Daniel J. Blackwell, Isabelle Marty, V. Ramesh Iyer, Bjorn C. Knollmann
Summary: CASQ2-K180R causes CPVT2 through impairing dynamic buffering of Ca within the SR, which is different from other CASQ2-related forms of CPVT2.
CIRCULATION RESEARCH
(2022)
Article
Physiology
Molly E. Streiff, Frank B. Sachse
Summary: The regulation of Ca2+ concentrations in cardiomyocytes is crucial for various physiological processes. Two types of Ca2+ currents, background Ca2+ entry and Ca2+ leak from the sarcoplasmic reticulum, play important roles in the modulation of Ca2+ transients and Ca2+ load. Our study provides quantitative insights into the individual contributions of these Ca2+ currents and supports the hypothesis that TRP channels are involved in cardiac contractility modulation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michael Arzt, Marzena A. Drzymalski, Sarah Ripfel, Sebastian Meindl, Alexander Biedermann, Melanie Durczok, Karoline Keller, Julian Mustroph, Sylvia Katz, Maria Tafelmeier, Simon Lebek, Bernhard Floerchinger, Daniele Camboni, Sigrid Wittmann, Johannes Backs, Christof Schmid, Lars S. Maier, Stefan Wagner
Summary: Patients with sleep-disordered breathing (SDB) have increased oxidized and activated CaMKII levels and CaMKII-dependent Ca spark frequency in the atrial myocardium, independent of major clinical confounders.
Article
Physiology
Adan Dagnino-Acosta, Agustin Guerrero-Hernandez
Summary: PKC inhibitors stimulate Ca2+ release from internal stores by increasing SR Ca2+ leak mediated by translocon activation. This increased leak does not deplete the Ca2+ store, but rather compensates by increasing SERCA pump activity, leading to a new steady-state level. This change also results in increased activity of high conductance, Ca2+-sensitive potassium channels.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Osha Roopnarine, Samantha L. Yuen, Andrew R. Thompson, Lauren N. Roelike, Robyn T. Rebbeck, Philip A. Bidwell, Courtney C. Aldrich, Razvan L. Cornea, David D. Thomas
Summary: In this study, FRET-based biosensors were used in live cells to screen small-molecules that can alter the structure and activity of SERCA2a, with the aim of discovering drug-like small-molecule activators for heart failure treatment. 50,000 compounds were screened, and 18 hit compounds were identified as SERCA modulators, with half being activators and half being inhibitors. Five promising SERCA activators were identified, one of which showed improved Ca2+-transport activity compared to Ca2+-ATPase activity. These findings provide a foundation for future testing and lead development for heart failure therapy.
SCIENTIFIC REPORTS
(2023)
Review
Cardiac & Cardiovascular Systems
Changwon Kho
Summary: Impaired myocardial Ca2+ cycling is a crucial factor in the development of heart failure, leading to changes in contractile function and structural remodeling of the heart. The regulation of sarcoplasmic reticulum Ca2+ storage and release in cardiomyocytes relies heavily on Ca2+ handling proteins like SERCA2a pump. However, reduced expression and activity of SERCA2a are key features of heart failure, resulting in a growing interest in therapeutic approaches targeting SERCA2a. This review provides an overview of the regulatory mechanisms of the SERCA2a pump and explores potential strategies for SERCA2a-targeted therapy in both preclinical and clinical studies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Amy D. Hanna, Chang Seok Lee, Lyle Babcock, Hui Wang, Joseph Recio, Susan L. Hamilton
Summary: The study indicates that the myopathy associated with the D244G mutation in CASQ1 is driven by CASQ1 mislocalization and aggregation, reduced SR calcium release, leading to ER stress, increased protein aggregation, and other pathological changes in muscle cells.
Article
Multidisciplinary Sciences
Roman Nikolaienko, Elisa Bovo, Daniel Kahn, Ryan Gracia, Thomas Jamrozik, Aleksey V. Zima
Summary: Common cardiac pathologies are associated with oxidative stress, leading to contractile dysfunction and arrhythmias. In this study, researchers identify two specific cysteines (1078 and 2991) in the RyR2 subunit that are responsible for the functional response to oxidative stress. These cysteines form a disulfide bond between neighboring subunits, causing pathological leaky RyR2 Ca2+ channels.
NATURE COMMUNICATIONS
(2023)
Article
Astronomy & Astrophysics
A. A. Aguilar-Arevalo, B. C. Brown, J. M. Conrad, R. Dharmapalan, A. Diaz, Z. Djurcic, D. A. Finley, R. Ford, G. T. Garvey, S. Gollapinni, A. Hourlier, E-C Huang, N. W. Kamp, G. Karagiorgi, T. Katori, T. Kobilarcik, K. Lin, W. C. Louis, C. Mariani, W. Marsh, G. B. Mills, J. Mirabal-Martinez, C. D. Moore, R. H. Nelson, J. Nowak, I Parmaksiz, Z. Pavlovic, H. Ray, B. P. Roe, A. D. Russell, A. Schneider, M. H. Shaevitz, H. Siegel, J. Spitz, I Stancu, R. Tayloe, R. T. Thornton, M. Tzanov, R. G. Van de Water, D. H. White, E. D. Zimmerman
Summary: The MiniBooNE experiment at Fermilab reported an excess of electronlike events from neutrino mode and antineutrino mode data samples, and conducted multiple studies on the source of the excess.
Article
Cardiac & Cardiovascular Systems
Ruben Lopez, Radoslav Janicek, Miguel Fernandez-Tenorio, Marianne Courtehoux, Lluis Matas, Pascale Gerbaud, Ana M. Gomez, Marcel Egger, Ernst Niggli
Summary: This study found that beta-adrenergic receptor (β-AR) activation and stimulation of SR Ca2+ pump (SERCA) can lead to higher frequencies of Ca2+ waves in cardiomyocytes with the RyR2R420Q+/- mutation. The phosphorylation of RyR2s and the resulting SR Ca2+ leak may play a role in this phenomenon.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yann Huey Ng, Regis R. Lamberts, Peter P. Jones, Ivan A. Sammut, Gary M. Diffee, Gerard T. Wilkins, James C. Baldi
Summary: This study found that impaired contractility in the diabetic heart is not caused by mishandling of calcium ion, suggesting that other factors, such as myofilament proteins, play a significant role in diabetic heart dysfunction.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Gustavo Montes Novaes, Enrique Alvarez-Lacalle, Sergio Alonso Munoz, Rodrigo Weber dos Santos
Summary: In this study, Markov Chain models were developed for L-type Calcium current in two established human cardiac models, maintaining the original whole-cell dynamics while enabling small spatial scale simulations of subcellular processes. The use of parameter collections was crucial for addressing model discrepancy, identifiability issues, and avoiding overfitting.
Article
Biophysics
Roman Nikolaienko, Elisa Bovo, Samantha L. Yuen, Levy M. Treinen, Kaja Berg, Courtney C. Aldrich, David D. Thomas, Razvan L. Cornea, Aleksey V. Zima
Summary: Compound 1 enhances SERCA2a Ca2+-ATPase and Ca2+ transport, improves intracellular Ca2+ dynamics, and has potential therapeutic effects for heart failure.
BIOPHYSICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Riley E. G. Cleverdon, Jessica L. Braun, Mia S. Geromella, Kennedy C. Whitley, Daniel M. Marko, Sophie I. Hamstra, Brian D. Roy, Rebecca E. K. MacPherson, Val A. Fajardo
Summary: Compared with C57 mdx mice, young D2 mdx mice show more severe impairment in SERCA function and higher levels of oxidative stress.
Review
Neurosciences
David A. Eisner
JOURNAL OF PHYSIOLOGY-LONDON
(2018)
Editorial Material
Physiology
D. A. Eisner
Editorial Material
Physiology
P. Bie, R. P. Brandes, S. A. Deuchars, D. A. Eisner, J. Fandrey, M. Hecker, W. E. Louch, T. Taira, B. Yilmaz
Review
Cardiac & Cardiovascular Systems
D. A. Eisner
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2018)
Review
Medicine, General & Internal
Cheuk Lee, Timea Beleznai, Salimah Hassan, Anju Rawat, Homeyra Douglas, Prathap Kanagala, Rajiv Sankaranarayanan
BRITISH JOURNAL OF HOSPITAL MEDICINE
(2019)
Article
Cardiac & Cardiovascular Systems
Charles M. Pearman, George W. P. Madders, Emma J. Radcliffe, Graeme J. Kirkwood, Michael Lawless, Amy Watkins, Charlotte E. R. Smith, Andrew W. Trafford, David A. Eisner, Katharine M. Dibb
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2018)
Review
Physiology
Nathan C. Denham, Charles M. Pearman, Jessica L. Caldwell, George W. P. Madders, David A. Eisner, Andrew W. Trafford, Katharine M. Dibb
FRONTIERS IN PHYSIOLOGY
(2018)
Editorial Material
Neurosciences
Laura Bennet, David A. Eisner, Alistair Jan Gunn
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Cardiac & Cardiovascular Systems
Rolf Wachter, Michele Senni, Jan Belohlavek, Ewa Straburzynska-Migaj, Klaus K. Witte, Zhanna Kobalava, Candida Fonseca, Eva Goncalvesova, Yuksel Cavusoglu, Alberto Fernandez, Said Chaabann, Ellen Bohmer, Anne-Catherine Pouleur, Christian Mueller, Christophe Tribouilloy, Eva Lonn, Jehad A. L. Buraiki, Jacek Gniot, Maria Mozheiko, Malgorzata Lelonek, Adele Noe, Heike Schwende, Weibin Bao, Dmytro Butylin, Domingo Pascual-Figal
EUROPEAN JOURNAL OF HEART FAILURE
(2019)
Article
Cardiac & Cardiovascular Systems
Rajiv Sankaranarayanan, Nick Hartshorne-Evans, Sam Redmond-Lyon, Jill Wilson, Hani Essa, Alastair Gray, Louise Clayton, Carys Barton, Fozia Z. Ahmed, Colin Cunnington, Duwarakan K. Satchithananda, Clare L. Murphy
Summary: The COVID-19 pandemic has caused significant anxiety among HF patients regarding COVID-19 and HF. Disruption to HF appointments, medication prescription services, and inability to access HF teams promptly were reported as sources of anxiety during the lockdown period.
Review
Cardiac & Cardiovascular Systems
Konstantinos Prokopidis, Masoud Isanejad, Asangaedem Akpan, Maria Stefil, Behnam Tajik, Panagiotis Giannos, Massimo Venturelli, Rajiv Sankaranarayanan
Summary: This article explores the potential contributions of exercise and nutritional interventions in the treatment of sarcopenia, frailty, and cardiorenal metabolic comorbidity in patients with heart failure. The majority of studies focus on resistance and aerobic exercises, as well as vitamin D and iron supplementation. However, there is a lack of experimental studies on the combined effect of exercise and nutrition in this population, calling for further research.
Article
Cardiac & Cardiovascular Systems
Jane Demmen, Nick Hartshorne-Evans, Elena Semino, Rajiv Sankaranarayanan
Summary: Heart failure is underdiscussed in contemporary English compared with cancer and dementia, as well as in UK parliamentary debates, even when compared with less-obviously life-threatening topics such as potholes in roads and pavements. The discussions of heart failure are more technical and formulaic, lacking survivor narratives that are prevalent in discussions of cancer.
Review
Cardiac & Cardiovascular Systems
Asma Gulab, Hani Essa, Kevin Bryan Lo, Rajiv Sankaranarayanan, Janani Rangaswami
Article
Medicine, General & Internal
Mrinalini Dey, Jagdish Nair, Rajiv Sankaranarayanan, Prathap Kanagala
Review
Cardiac & Cardiovascular Systems
David A. Eisner, Jessica L. Caldwell, Kornel Kistamas, Andrew W. Trafford
CIRCULATION RESEARCH
(2017)