Article
Cardiac & Cardiovascular Systems
Javier Barallobre-Barreiro, Tamas Radovits, Marika Fava, Ursula Mayr, Wen-Yu Lin, Elizaveta Ermolaeva, Diego Martinez-Lopez, Eric L. Lindberg, Elisa Duregotti, Laszlo Daroczi, Maria Hasman, Lukas E. Schmidt, Bhawana Singh, Ruifang Lu, Ferheen Baig, Aleksandra Malgorzata Siedlar, Friederike Cuello, Norman Catibog, Konstantinos Theofilatos, Ajay M. Shah, Maria G. Crespo-Leiro, Nieves Domenech, Norbert Hubner, Bela Merkely, Manuel Mayr
Summary: The study identified ADAMTS5 protease as critical for versican degradation in the heart and found that versican accumulation is associated with impaired cardiac function in heart failure patients and animal models. Versikine, an ADAMTS-specific cleavage product, accumulated in ischemic heart failure patients and following cardiac ischemia/reperfusion injury in animal models. The use of beta-blockers in heart failure patients was associated with a reduction in ECM deposition, particularly in the levels of versican, indicating a potential beneficial effect on cardiac chondroitin sulfate proteoglycan content.
Article
Cardiac & Cardiovascular Systems
Dunja Aksentijevic, Michael J. Shattock
Summary: Elevated intracellular sodium and metabolic impairment are common features of heart failure. Studies have shown that sodium elevation affects mitochondrial function, providing important insights into the pathophysiology of heart failure and potential treatment strategies.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Anne Garnier, Nadja Bork, Eric Jacquet, Svante Zipfel, Christian Munoz-Guijosa, Istvan Baczko, Hermann Reichenspurner, Patrick Donzeau-Gouge, Lars S. Maier, Dobromir Dobrev, Evaldas Girdauskas, Viacheslav O. Nikolaev, Rodolphe Fischmeister, Cristina E. Molina
Summary: This study compares the expression profiles of key genes involved in the cAMP signaling cascade in human right and left atrial appendages across different cardiac pathologies. The results show specific patterns of gene expression changes in different diseases, providing insights into the molecular mechanisms underlying atrial diseases.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Mordecai P. Blaustein, Stephen S. Gottlieb, John M. Hamlyn, Frans H. H. Leenen
Summary: The cloning of Na-K ATPase and the identification of endogenous ouabain (EO) have led to significant discoveries in the cardiovascular function, heart failure, and hypertension. Digoxin, although not very effective in a clinical trial, has been found to lower blood pressure in hypertension models. Digoxin and ouabain affect different protein kinase signaling pathways, and ouabain plays a slow neuromodulatory role in the brain. The roles of ouabain and α2 NKA are closely related to the development of hypertension and heart failure.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Miles A. Tanner, Charles A. Maitz, Laurel A. Grisanti
Summary: This study demonstrates the important role of immune cell beta(2)AR in regulating inflammation and cardiac function in response to chronic catecholamine elevations. Mice lacking immune cell beta(2)AR showed decreased immune cell infiltration and improved cardiac outcomes when exposed to beta AR agonist isoproterenol. The findings suggest that beta(2)AR regulation of immune responses is crucial for the heart's response to prolonged beta adrenergic stimulation.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Mathieu Cinato, Laurie Guitou, Amira Saidi, Andrei Timotin, Erwan Sperazza, Thibaut Duparc, Sergey N. Zolov, Sai Srinivas Panapakkam Giridharan, Lois S. Weisman, Laurent O. Martinez, Jerome Roncalli, Oksana Kunduzova, Helene Tronchere, Frederic Boal
Summary: The study highlights the inhibitory effects of Apilimod on cardiac fibrotic remodeling, controlling the TGF beta signaling pathway to prevent adverse remodeling. It also suggests a novel function for PIKfyve in regulating myocardial fibrosis and TGF beta pathway.
Article
Cardiac & Cardiovascular Systems
Kimberly J. McCabe, Padmini Rangamani
Summary: The cAMP/PKA pathway plays a crucial role in regulating excitation-contraction coupling in cardiomyocytes, with downstream effects on cardiac function. Experimental advances have revealed compartmentation of cAMP and PKA, while computational modeling helps to understand the spatial and temporal complexities of this system. Various compartmental and spatial signaling models have been used to study adrenergic signaling pathways in different simulation conditions, with newer subcellular models of cardiovascular function being explored for future study.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Medicine, Research & Experimental
Xuemei Wei, Andi Zhang, Wenbo Yang, Yuehua Fang
Summary: Depletion of ADRB3 alleviates pressure overload-induced cardiac hypertrophy and heart failure by enhancing the innate immune response in the heart, as demonstrated in a study using ADRB3-knockout mice undergoing TAC surgery.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Maradumane L. Mohan, Yuji Nagatomo, Prasenjit Prasad Saha, Sromona D. Mukherjee, Timothy Engelman, Rommel Morales, Stanley L. Hazen, W. H. Wilson Tang, Sathyamangla V. Naga Prasad
Summary: Dysregulation of immune responses can lead to the generation of IgG autoantibodies targeting human beta 1ARs, which contribute to negative cardiac outcomes. However, beta-blockers have shown benefits in patients with IgG3 autoantibodies, suggesting a potential role of these autoantibodies in altering beta 1AR function. Further investigation revealed that IgG3 autoantibodies bias beta-blockers towards G-protein coupling and alter signaling, leading to beneficial outcomes in patients.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Cardiac & Cardiovascular Systems
Andres Pun-Garcia, Agustin Clemente-Moragon, Rocio Villena-Gutierrez, Monica Gomez, David Sanz-Rosa, Anabel Diaz-Guerra, Belen Prados, Juan Pablo Medina, Fermi Monto, Maria Dolores Ivorra, Cristina Marquez-Lopez, Alessandro Cannavo, Juan A. Bernal, Walter J. Koch, Valentin Fuster, Jose Luis de la Pompa, Eduardo Oliver, Borja Ibanez
Summary: This study suggests that beta 3AR overexpression may be beneficial in treating HF induced by AS, indicating a potential therapeutic strategy.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Article
Biology
Xin Shen, Jonas van den Brink, Anna Bergan-Dahl, Terje R. Kolstad, Einar S. Norden, Yufeng Hou, Martin Laasmaa, Yuriana Aguilar-Sanchez, Ann P. Quick, Emil K. S. Espe, Ivar Sjaastad, Xander H. T. Wehrens, Andrew G. Edwards, Christian Soeller, William E. Louch
Summary: This study investigates the promotion of RyR cluster dispersion by prolonged beta-adrenergic stimulation in heart failure, and examines the underlying mechanisms. The findings demonstrate the intimate connection between RyR localization and function through channel phosphorylation by CaMKII and PKA, which plays a protective role in healthy cardiomyocytes but contributes to impaired cardiac function during heart failure.
Review
Pharmacology & Pharmacy
Ahmed Rakib, Taslima Akter Eva, Saad Ahmed Sami, Saikat Mitra, Iqbal Hossain Nafiz, Ayan Das, Abu Montakim Tareq, Firzan Nainu, Kuldeep Dhama, Talha Bin Emran, Jesus Simal-Gandara
Summary: Heart failure is a complex clinical syndrome that is often the result of long-standing hypertension. Recent advances in hypertension treatment include novel pathways such as the potential role of beta-arrestin in regulating hypertension. However, there are still controversies surrounding the roles of the two beta-arrestin isoforms in the treatment of HF.
Article
Cardiac & Cardiovascular Systems
Abrahim Mahmood, Kinza Ahmed, Youhua Zhang
Summary: Cardiac sympathetic activation and abnormal Ca2+ handling are important factors in the progression of heart failure. The interaction between beta-adrenergic receptor desensitization/down-regulation and abnormal Ca2+ handling in heart failure leads to cardiac dysfunction and arrhythmias.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Jean-Luc Balligand, Lauriane Y. M. Michel
Summary: This article discusses the benefits and safety of beta 3-adrenoreceptor agonists on cardiovascular outcomes. Based on limited evidence from small clinical trials, mirabegron, a beta 3-agonist, appears to be safe in patients at high cardiovascular risk but only produces benefits on selected cardiovascular outcomes at higher doses. Testing more potent beta 3-adrenoreceptor agonists, such as vibegron, is necessary.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2023)
Article
Plant Sciences
Rubin Tan, Qiang You, Jie Cui, Mingming Wang, Nina Song, Ke An, Lili Lin, Joseph Adu-Amankwaah, Jinxiang Yuan, Hong Sun
Summary: This study found that Sodium houttuyfonate (SH) can directly inhibit the activation and proliferation of cardiac fibroblasts by binding to MMP2 and p38, thereby delaying the progression of cardiac fibrosis and heart failure (HF).
Editorial Material
Cardiac & Cardiovascular Systems
Alice Main, Olivia Robertson-Gray, William Fuller
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Andrii Boguslavskyi, Sergiy Tokar, Oleksandra Prysyazhna, Olena Rudyk, David Sanchez-Tatay, Hamish A. L. Lemmey, Kim A. Dora, Christopher J. Garland, Helen R. Warren, Alexander Doney, Colin N. A. Palmer, Mark J. Caulfield, Julia Vlachaki Walker, Jacqueline Howie, William Fuller, Michael J. Shattock
Summary: Studies have shown the significance of phospholemman phosphorylation in regulating vascular tone and blood pressure, suggesting it as a potential novel mechanism and therapeutic target for aging-induced essential hypertension in humans.
Review
Biochemistry & Molecular Biology
Alice Main, William Fuller
Summary: This review discusses the role of lipid post-translational modification S-palmitoylation in diseases and the advancements in experimental tools in the field. Understanding how palmitoylation controls protein localization and function may lead to its modulation as a therapeutic strategy in the future.
Article
Cell Biology
Caglar Gok, Alan D. Robertson, William Fuller
Summary: In this study, we found that insulin regulates the activity of NCX1 by inducing its palmitoylation, thereby modulating Ca2+ handling in cardiac cells. By activating fatty acid and fatty acyl CoA synthesis, insulin promotes palmitoylation of the zDHHC5 active site, leading to enhanced NCX1 palmitoylation.
Article
Physiology
Huiying Ren, Zhaoli Pu, Tianyi Sun, Tangting Chen, Leiying Liu, Zhu Liu, Christopher O'Shea, Davor Pavlovic, Xiaoqiu Tan, Ming Lei
Summary: The article presents a 3D heart imaging reconstruction approach by combining an improved heart tissue-clearing technique with high-resolution light-sheet fluorescence microscopy. The approach allows for the study of specific cell types in organs and their spatial distributions and characteristics.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Christopher O'Shea, James Winter, S. Nashitha Kabir, Molly O'Reilly, Simon P. Wells, Olivia Baines, Laura C. Sommerfeld, Joao Correia, Ming Lei, Paulus Kirchhof, Andrew P. Holmes, Larissa Fabritz, Kashif Rajpoot, Davor Pavlovic
Summary: Optical mapping is a widely used technique in pre-clinical cardiac research, allowing for efficient study of cardiac electrophysiology and the effects of interventions on arrhythmia.
Article
Urology & Nephrology
Sudha Priya Soundara Pandi, Michael J. Shattock, Bruce M. Hendry, Claire C. Sharpe
Summary: The role of different isoforms of TTCC in mouse mesangial cells was investigated in this study to determine the best therapeutic target for treating mesangioproliferative kidney diseases. Single and double knockout clones of the TTCC isoforms Ca(V)3.1 and Ca(V)3.2 were generated using CRISPR-cas9 gene editing. It was found that the Ca(V)3.1 isoform is required for stimulated phosphorylation of ERK1/2, while the Ca(V)3.2 isoform is not. Neither isoform was necessary for cell proliferation, and the anti-proliferative effects of mibefradil and TH1177 were not isoform-specific.
Review
Peripheral Vascular Disease
Jonathan P. Law, Luke Pickup, Davor Pavlovic, Jonathan N. Townend, Charles J. Ferro
Summary: Chronic kidney disease (CKD) is a complex condition that affects 10-15% of the global population. There is an inverse relationship between kidney function and cardiovascular events and mortality, independent of age, sex, and other risk factors. The development of CKD-associated cardiomyopathy, characterized by left ventricular changes and fibrosis, is significantly influenced by hypertension. Even in mild to moderate renal impairment, structural and functional changes consistent with CKD-associated cardiomyopathy can be observed.
JOURNAL OF HUMAN HYPERTENSION
(2023)
Letter
Cardiac & Cardiovascular Systems
Daniel M. Johnson, Davor Pavlovic
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Matthew Ackers-Johnson, Roger S. Foo, Davor Pavlovic
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Juan F. Cervilla-Martinez, Juan J. Rodriguez-Gotor, Krzysztof J. Wypijewski, Angela Fontan-Lozano, Tao Wang, Enrique Santamaria, William Fuller, Rebeca Mejias
Summary: Through data-mining of palmitome in the cerebral cortex of PD patients and controls, the study identified 150 proteins with altered palmitoylation, which are predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. The research suggests that protein palmitoylation may play a role in the pathophysiology of PD, and comprehensive palmitoyl-proteomics is a powerful approach for exploring novel cellular pathways involved in this neurodegenerative disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
William Fuller
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Dylan Chase, Thomas R. Eykyn, Michael J. Shattock, Yu Jin Chung
Summary: This study aims to test whether EMPA directly alters cardiac ketone metabolism independent of supply.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Jie Su, Pierre Coleman, Angeliki Ntorla, Rhys Anderson, Michael J. Shattock, Joseph R. Burgoyne
Summary: This study demonstrates that the cytosolic DNA sensor cGAS can activate PKGI directly through the generation of cGAMP, showing a link between inflammation and blood pressure regulation.
Article
Physiology
Simon P. Wells, Antonia J. A. Raaijmakers, Claire L. Curl, Christopher O'Shea, Sarah Hayes, Kimberley M. Mellor, Jonathan M. Kalman, Paulus Kirchhof, Davor Pavlovic, Lea M. D. Delbridge, James R. Bell
Summary: This study demonstrates that the transmural conduction gradient in rat ventricular slices is abolished when there is increased pericardial adiposity, with slowed epicardial conduction correlating with an increase in cardiomyocyte lipid content. This gradient is important in reducing vulnerability to arrhythmias, and its absence due to conduction slowing and cardiomyocyte lipid accumulation suggests a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)