Article
Cell Biology
Marcin Moch, Jana Schieren, Rudolf E. Leube
Summary: Mechanical stress affects the plasticity of desmosomes and regulates the turnover of desmosomal proteins, suggesting the existence of a yet unknown mechanosensing pathway in desmosomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sunil Yeruva, Konstanze Stangner, Anna Jungwirth, Matthias Hiermaier, Maria Shoykhet, Daniela Kugelmann, Michael Hertl, Shohei Egami, Norito Ishii, Hiroshi Koga, Takashi Hashimoto, Michael Weis, Britt-Maria Beckmann, Ruth Biller, Dominik Schuettler, Stefan Kaeaeb, Jens Waschke
Summary: This study found that autoantibodies targeting intercalated disc (ICD) proteins are common in patients with arrhythmogenic cardiomyopathy (AC) and have catalytic properties, cleaving the ICD adhesion molecules and reducing cardiomyocyte cohesion. Additionally, these autoantibodies activate the p38MAPK pathway, exacerbating the detachment of cardiomyocytes. Therefore, cleavage of ICD proteins by autoantibodies could serve as a diagnostic tool for AC.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Medicine, Research & Experimental
Baowei Zhang, Yizhang Wu, Xingbo Yang, Yaozu Xiang, Bing Yang
Summary: Mutant DSG2 is the second most common pathogenic gene in ACM, causing specific characteristics such as left ventricle involvement and high risk of heart failure. Desmosome dysfunction and dysregulated inflammation, growth factor signaling, and cardiac metabolism contribute to the pathogenesis of this disease.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cardiac & Cardiovascular Systems
Greta Marie Pohl, Manuel Goez, Anna Gaertner, Andreas Brodehl, Tolga Cimen, Ardan M. Saguner, Eric Schulze-Bahr, Volker Walhorn, Dario Anselmetti, Hendrik Milting
Summary: In this study, we found that several variants at specific positions in the prodomain of cardiac desmosomal cadherins can influence intracellular transport. However, some commonly listed variants in genetic databases do not affect intracellular transport. These prodomain variants may be relevant in the context of arrhythmogenic cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyu Liu, Mingru Bai, Yimin Sun, Xuchen Hu, Chenglin Wang, Jing Xie, Ling Ye
Summary: In osteoblasts, FGF7 promotes the expression of E11, leading to dendrites elongation and the formation of functional gap junctions through connexin43 (Cx43) interaction. This process is mediated by the MAPK pathway and PI3K-AKT pathway, suggesting a significant role of FGF7 in later stages of bone development and homeostasis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jin Kono, Masakatsu Ueda, Atsushi Sengiku, Sylvia O. Suadicani, Osamu Ogawa, Hiromitsu Negoro
Summary: The study suggests that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals' awake, active phase. This research highlights the significant role of Cx43 in bladder function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Carlos Bueno-Beti, Angeliki Asimaki
Summary: Arrhythmogenic cardiomyopathy (ACM) is associated with ventricular arrhythmias and sudden cardiac death. Recent studies have shown that buccal cells behave similarly to the heart in terms of protein re-localization, which provides a potential alternative for diagnosis, risk stratification, and monitoring of pharmaceutical interventions for ACM.
Article
Cell Biology
Zuping Wu, Chenchen Zhou, Quan Yuan, Demao Zhang, Jing Xie, Shujuan Zou
Summary: CTGF promotes intercellular communication in chondrocytes through upregulating Cx43 expression and activating the PI3K/Akt signaling pathway.
CELL PROLIFERATION
(2021)
Article
Cell Biology
K. E. Ng, P. J. Delaney, D. Thenet, S. Murtough, C. M. Webb, N. Zaman, E. Tsisanova, G. Mastroianni, S. L. M. Walker, J. D. Westaby, D. J. Pennington, R. Pink, D. P. Kelsell, A. Tinker
Summary: The study revealed that cardiac inflammation is a key early event leading to fibrosis in arrhythmogenic cardiomyopathy. Loss of desmoglein 2 in the young murine heart resulted in apoptosis and upregulation of inflammatory-associated pathways, suggesting an early immune response triggers tissue remodelling in the fibrotic heart. This analysis indicates that cardiac inflammation plays an important role in AC disease progression.
CELL AND TISSUE RESEARCH
(2021)
Article
Biology
Mingyang Huang, Anying Song, Xi Chen, Sarah Ishtiaq, Chunmei Wang, Darryl L. Hadsell, Qiong A. Wang, Yi Zhu
Summary: Breastfeeding offers health benefits for both mothers and infants, but the increase in obesity in the U.S. has made it difficult for many mothers to produce and express breastmilk. The quality of breastmilk from obese mothers is also compromised. This study investigates the role of Connexin43 in adipocyte remodeling and breastmilk production, suggesting that enhancing adipocyte Connexin43 may help obese mothers produce better breastmilk to support their neonates' growth.
Article
Oncology
Francesca Reimer, Sarah Bryan, Karen Legler, Thomas Karn, Serenella Eppenberger-Castori, Jakob Matschke, Thais Pereira-Veiga, Harriet Wikman, Isabell Witzel, Volkmar Mueller, Barbara Schmalfeldt, Karin Milde-Langosch, Udo Schumacher, Christine Stuerken, Leticia Oliveira-Ferrer
Summary: This study demonstrates the pro-metastatic role of desmocollin 2 (DSC2) in breast cancer. Increased DSC2 expression was found in HER2-positive and triple negative breast cancers, and was significantly associated with shorter disease-free and overall survival. In vitro and in vivo experiments showed that DSC2 overexpression promoted tumor cell aggregation and chemoresistance, while DSC2 knock down reduced circulating tumor cells/clusters and brain metastatic lesions.
CANCER CELL INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Micah W. W. Yoder, Nathan T. T. Wright, Maegen A. A. Borzok
Summary: The intercalated disk in the heart is a structure composed of adherens junctions, desmosomes, and gap junctions, which provide mechanical stability and electrical synchronization. Calpain proteases, regulated by calcium homeostasis, play an important role in regulating the components of the intercalated disk. This review examines the role of calcium in calpain function, how calpains regulate the activity of specific proteins in the intercalated disk, and the molecular mechanisms behind calpain dysregulation and its impact on heart diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Reproductive Biology
Lin Yin, Wusu Wang, Weijun Pang, Gongshe Yang, Lei Gao, Guiyan Chu
Summary: Gap junction intercellular communication plays an important role in follicular development. In porcine follicles, Cx43 is the most widely expressed connexin. Insulin can enhance Cx43 protein expression, which is dependent on the phosphorylated activities of AKT and Erk.
Article
Dermatology
Hiroshi Koga, Kwesi Teye, Yoshihiko Otsuji, Norito Ishii, Takashi Hashimoto, Takekuni Nakama
Summary: This study analyzed the characteristics of anti-DSC3 antibodies in Pemphigus patients, revealing a predominant recognition of a calcium-dependent epitope in the EC2 domain of DSC3 by these antibodies, and their pathogenicity on keratinocyte adhesion through DSC3 depletion.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Review
Endocrinology & Metabolism
Ceren Canse, Ecem Yildirim, Aylin Yaba
Summary: Cell-cell junctions play crucial roles in maintaining cell integrity, polarity, cell fate specification, and morphogenesis during embryonic development. By orchestrating mechanotransduction, morphokinetics, and signaling networks, these junctions, along with cell adhesion molecules and cytoskeletal elements, regulate the development of early embryos. This review focuses on the structure, organization, function, and expression pattern of cell-cell junction complexes during early embryonic development. Understanding the importance of dynamic junction formation and maturation processes will provide insights into the molecular mechanisms underlying developmental abnormalities in early embryos.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Sheng-Chia Chung, Alvina Lai, Gregory Y. H. Lip, Pier D. Lambiase, Rui Providencia
Summary: Using real-world data from the UK, this study aimed to investigate the effectiveness of anti-arrhythmic drugs and catheter ablation in improving the survival of atrial fibrillation patients. The study found that patients receiving rhythm control treatment had lower mortality rates, with pulmonary vein isolation showing the most pronounced survival benefit.
Article
Cardiac & Cardiovascular Systems
Peter H. Waddingham, Jan O. Mangual, Michele Orini, Nima Badie, Amal Muthumala, Simon Sporton, Luke C. McSpadden, Pier D. Lambiase, Anthony W. C. Chow
Summary: This study assessed the impact of dynamic AV delay programming using SyncAV on electrical dyssynchrony across various pacing modalities. The results showed that dynamic AV delay programming significantly reduced dyssynchrony for all evaluated pacing modes, with MPP + SyncAV achieving the greatest synchrony overall.
Editorial Material
Cardiac & Cardiovascular Systems
Pier D. Lambiase, Prashantan Sanders, Harry J. G. M. Crijns
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Robert D. Anderson, Sachin Nayyar, Stephane Masse, Pier D. Lambiase, Kumaraswamy Nanthakumar
Summary: The re-emerging interest in ventricular electrophysiology and repolarization has led to the development of wave tail mapping, which can identify critical sites beyond the traditional depolarization mapping techniques. While various techniques can study diseased substrate in detail, clinical outcomes remain unchanged. Wave tail mapping has the potential to fill this gap, particularly in cases where conventional scar ablation endpoints are limited. However, there are barriers to its clinical use, and further improvements in repolarization mapping are needed.
Article
Cardiac & Cardiovascular Systems
Christopher Monkhouse, Amy Wharmby, Zoe Carter, Ross Hunter, Mehul Dhinoja, Anthony Chow, Antonio Creta, Shohreh Honarbakhsh, Syed Ahsan, Michele Orini, Pier D. Lambiase
Summary: The aim of this study was to evaluate the impact of the SMART Pass (TM) algorithm on inappropriate therapy (IT) in subcutaneous internal cardiac defibrillator (S-ICD) and to explore the association between SP deactivation and IT. The results showed that SP deactivation was significantly associated with an increased risk of IT, and changing the sensing vector was successful in preventing IT.
Letter
Cardiac & Cardiovascular Systems
Jaffar Al-Sheikhli, James Winter, Ivo Roca Luque, Pier D. Lambiase, Michele Orini, Andreu Porta-Sanchez, Tarvinder Dhanjal
Article
Cardiac & Cardiovascular Systems
Shohreh Honarbakhsh, Claire A. Martin, Gurpreet Dhillon, Mark Gallagher, Manav Sohal, Anthony Chow, Syed Ahsan, Hakam Abbass, Sarah Whittaker-Axon, Pier D. Lambiase, Mark J. Davies, Matthew Ginks, Ross J. Hunter
Summary: This study evaluated the effectiveness and safety of high power short duration (HPSD) ablation for atrial fibrillation ablation. The results showed that HPSD ablation can effectively achieve pulmonary vein isolation and has advantages in procedural time, ablation time, and reconnection rate.
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
William J. Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R. Harper, Julia Ramirez, Sophie Garnier, Stefan van Duijvenboden, Antoine R. Baldassari, Maria Pina Concas, ThuyVy Duong, Luisa Foco, Jonas L. Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L. Santolalla, Colleen M. Sitlani, Negin Soroush, Sebastien Theriault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A. Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-Francois Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R. Heckbert, Rebecca D. Jackson, Jan A. Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W. Macfarlane, Alanna C. Morrison, Pau Navarro, David J. Porteous, Peter P. Pramstaller, Alexander P. Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z. Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R. Warren, Eric A. Whitsel, Kerri L. Wiggins, Dan E. Arking, Christy L. Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J. Wouter Jukema, Dennis O. Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M. Psaty, Cristian Pattaro, Antonio Luiz P. Ribeiro, Jerome I. Rotter, Bruno H. Stricker, Pim van der Harst, Cornelia M. van Duijn, Niek Verweij, James G. Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J. Lin, James F. Wilson, Jrgen K. Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D. Lambiase, Larisa G. Tereshchenko, Patricia B. Munroe
Summary: Using multi-ancestry genome-wide association studies, this research identified 61 loci related to spatial QRS-T angle and 11 loci related to frontal QRS-T angle. These loci also showed shared genetic influences with classical ECG traits and were associated with cardiovascular diseases. The findings provide insights into the biology of QRS-T angles and their relationships with cardiovascular traits and diseases, which can inform future research and risk prediction.
NATURE COMMUNICATIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Stefan van Duijvenboden, Julia Ramirez, Michele Orini, Nay Aung, Steffen E. Petersen, Aiden Doherty, Andrew Tinker, Patricia B. Munroe, Pier D. Lambiase
Summary: This study found that exercise-induced premature ventricular contractions (PVCs) are closely associated with major adverse cardiovascular events, all-cause mortality, and heart failure in asymptomatic individuals. The risk increases as the PVC burden increases, and complex PVC rhythms pose a higher risk compared to PVC count alone. The study also suggests the presence of subclinical cardiomyopathy.
Article
Cardiac & Cardiovascular Systems
George Joy, Christopher I. Kelly, Matthew Webber, Iain Pierce, Irvin Teh, Louise Mcgrath, Paula Velazquez, Rebecca K. Hughes, Huafrin Kotwal, Arka Das, Fiona Chan, Athanasios Bakalakos, Massimiliano Lorenzini, Konstantinos Savvatis, Saidi A. Mohiddin, Peter W. Macfarlane, Michele Orini, Charlotte Manisty, Peter Kellman, Rhodri H. Davies, Pier D. Lambiase, Christopher Nguyen, Jurgen E. Schneider, Maite Tome, Gabriella Captur, Erica Dall'Armellina, James C. Moon, Luis R. Lopes
Summary: In patients with hypertrophic cardiomyopathy, alterations in myocardial microstructure and microvascular disease have been found to occur early in the disease process. These changes serve as potential early phenotype biomarkers for disease detection and management.
Article
Cardiac & Cardiovascular Systems
Mark J. Specterman, Qadeer Aziz, Yiwen Li, Naomi A. Anderson, Leona Ojake, Keat-Eng Ng, Alison M. Thomas, Malcolm C. Finlay, Richard J. Schilling, Pier D. Lambiase, Andrew Tinker
Summary: This study investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of the K-ATP pore-forming subunits. The results showed that K-ATP blockade or absence resulted in atrial electrophysiological modifications at the cellular and tissue level. Furthermore, the global knockout of Kir6.2 prevented hypoxia-induced atrial path length shortening and arrhythmogenicity, suggesting a potential translational approach for treating ischemically driven atrial arrhythmia.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Pier D. Lambiase
Article
Cardiac & Cardiovascular Systems
Gurpreet Dhillon, Shohreh Honarbakhsh, Hakam Abbas, Peter Waddingham, Adam S. Dennis, Nikhil Ahluwalia, Malcolm Finlay, Afzal Sohaib, Sophie Welch, Holly Daw, Simon Sporton, Anthony Chow, Mark J. Earley, Pier D. Lambiase, Ross J. Hunter
Summary: This study evaluated the clinical outcomes and response to ablation of potential drivers in patients with recurrent persistent AF following pulmonary vein isolation (PVI). The study found that ECGI-guided ablation caused an acute response in a majority of patients and had reasonable long-term outcomes.
Article
Cardiac & Cardiovascular Systems
Rebecca K. Hughes, Joao B. Augusto, Kristopher Knott, Rhodri Davies, Hunain Shiwani, Andreas Seraphim, James W. Malcolmson, Shafik Khoury, George Joy, Saidi Mohiddin, Luis R. Lopes, William J. McKenna, Peter Kellman, Hui Xue, Maite Tome, Sanjay Sharma, Gabriella Captur, James C. Moon
Summary: This study found that apical perfusion defects are universally present in ApHCM patients, suggesting that ischemia may play a disease-defining role in ApHCM, which is supported by characteristic ECG results.
CIRCULATION-CARDIOVASCULAR IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Charles Butcher, Caroline Roney, Amy Wharmby, Nikhil Ahluwalia, Anthony Chow, Pier D. Lambiase, Ross J. Hunter, Shohreh Honarbakhsh
Summary: This study evaluated different methods for assessing atrial voltage and their accuracy in identifying pulmonary vein reconnection sites (PVRSs) in atrial fibrillation (AF). The results showed that omnipoar voltage atrial fibrillation (OV AF) maps improve voltage assessment by overcoming the impact of wavefront collision and fractionation, leading to improved accuracy.
JACC-CLINICAL ELECTROPHYSIOLOGY
(2023)