Article
Cardiac & Cardiovascular Systems
Luzi Yang, Jinhuan Sun, Zhan Chen, Lei Liu, Yueshen Sun, Junsen Lin, Xiaomin Hu, Mingming Zhao, Yuanwu Ma, Dan Lu, Yifei Li, Yuxuan Guo, Erdan Dong
Summary: The LMNA c.1621C > T/ p.R541C variant contributes to dilated cardiomyopathy (DCM) by enhancing heterochromatic gene suppression and disrupting mitochondrial functions.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuval Shemer, Lucy N. Mekies, Ronen Ben Jehuda, Polina Baskin, Rita Shulman, Binyamin Eisen, Danielle Regev, Eloisa Arbustini, Brenda Gerull, Mihaela Gherghiceanu, Eyal Gottlieb, Michael Arad, Ofer Binah
Summary: LMNA-related dilated cardiomyopathy is an inherited heart disease characterized by left ventricular enlargement and impaired systolic function caused by mutations in the LMNA gene, leading to abnormalities in cardiac physiology and gene expression. Studying induced pluripotent stem cell-derived cardiomyocytes from patients can provide insights into potential therapeutic strategies for the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Kiran Sidhu, Anna Isotta Castrini, Victoria Parikh, Nosheen Reza, Anjali Owens, Maxime Tremblay-Gravel, Matthew T. Wheeler, Luisa Mestroni, Matthew Taylor, Sharon Graw, Marta Gigli, Marco Merlo, Alessia Paldino, Gianfranco Sinagra, Daniel P. Judge, Hannia Ramos, Olurotimi Mesubi, Emily Brown, Samual Turnbull, Saurabh Kumar, Darius Roy, Usha B. Tedrow, Long Ngo, Kristina Haugaa, Neal K. Lakdawala
Summary: Cardiac resynchronization therapy (CRT) plays an important role in improving heart failure in LMNA cardiomyopathy patients, especially in those with strong guideline indications. The study found that patients who responded to CRT had improved systolic function and experienced survival benefits.
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Article
Cardiac & Cardiovascular Systems
Kenji Onoue, Hiroko Wakimoto, Jiangming Jiang, Michael Parfenov, Steven DePalma, David Conner, Joshua Gorham, David McKean, Jonathan G. Seidman, Christine E. Seidman, Yoshihiko Saito
Summary: The mutation of LMNA gene contributes to the development of DCM by impairing cell proliferation capacity and cell cycle defects, which is distinct from the mechanisms of other causative genes of DCM.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Antonia Gonzalez-Garrido, Sandra Rosas-Madrigal, Arturo Rojo-Dominguez, Jaime Arellanes-Robledo, Enrique Lopez-Mora, Alessandra Carnevale, Leticia Arregui, Rigoberto Rosendo-Gutierrez, Sandra Romero-Hidalgo, Maria Teresa Villarreal-Molina
Summary: The clinical phenotype of LMNA-associated dilated cardiomyopathy (DCM) varies even among individuals who share the same mutation. LAP2 alpha/Arg690Cys polymorphism may be one of the many factors contributing to phenotype variation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yongping Lin, Hailei Liu, Chang Cui, Zhiqiao Lin, Yike Zhang, Yue Zhu, Weizhu Ju, Minglong Chen
Summary: A novel frameshift mutation (p.P485Tfs*67) in the LMNA gene was identified in a patient with early-onset atrial disease. A transgenic zebrafish model confirmed the pathogenicity of this mutation, showing abnormal ECG and impaired myocardial structure in adult zebrafish, suggesting the atrial pathogenicity of the LMNA-P485Tfs mutation and providing insights into the function of the Ig-like domain of lamin A/C.
HUMAN MOLECULAR GENETICS
(2021)
Article
Cell & Tissue Engineering
Yuzuno Shimoda, Nobuyuki Murakoshi, Haruka Mori, DongZhu Xu, Kazuko Tajiri, Yasuko Hemmi, Iori Sato, Michiya Noguchi, Yukio Nakamura, Yohei Hayashi, Masaki Ieda
Summary: A human induced pluripotent stem cell line derived from a patient with DCM carrying a LMNA mutation has been established, providing a valuable resource for studying disease mechanisms and developing treatments for LMNA-related DCM.
STEM CELL RESEARCH
(2022)
Article
Medicine, General & Internal
Valentina Ferradini, Joseph Cosma, Fabiana Romeo, Claudia De Masi, Michela Murdocca, Paola Spitalieri, Sara Mannucci, Giovanni Parlapiano, Francesca Di Lorenzo, Annamaria Martino, Francesco Fedele, Leonardo Calo, Giuseppe Novelli, Federica Sangiuolo, Ruggiero Mango
Summary: LMNA gene mutations account for familial dilated cardiomyopathy, which presents with a variety of symptoms and can lead to sudden cardiac death. Genetic testing and phenotype correlation studies help further understand the disease. Research findings suggest that LMNA variants significantly affect nuclear morphology and lamin expression.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cell Biology
Yinuo Wang, Gergana Dobreva
Summary: Mutations in the LMNA gene cause laminopathies, a group of diverse diseases. LMNA-related cardiomyopathy is a common inherited heart disease with a poor prognosis. Research using mouse models, stem cells, and patient samples has characterized the phenotypic diversity caused by LMNA variants and contributed to understanding the molecular mechanisms underlying heart disease. This review focuses on the different cardiomyopathies caused by LMNA mutations, the role of LMNA in chromatin organization and gene regulation, and how these processes are disrupted in heart disease.
Article
Cardiac & Cardiovascular Systems
Anna Castrini, Eystein Skjolsvik, Mette E. Estensen, Vibeke M. Almaas, Helge Skulstad, Erik Lyseggen, Thor Edvardsen, Oyvind H. Lie, Kermshlise C. Picard, Neal K. Lakdawala, Kristina H. Haugaa
Summary: In women with LMNA+ gene variants, the number of pregnancies does not appear to be associated with increased long-term risk of cardiac dysfunction, arrhythmias, or decreased event-free survival. Pregnancy is generally well-tolerated by women with LMNA+, with a low proportion experiencing arrhythmias during pregnancy.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Calum A. MacRae, Matthew R. G. Taylor, Luisa Mestroni, John Moses, Euan A. Ashley, Matthew T. Wheeler, Neal K. Lakdawala, Ray E. Hershberger, Victor Sandor, Michael E. Saunders, Colleen Oliver, Patrice A. Lee, Daniel P. Judge
Summary: This study assessed the effects of ARRY-371797, an oral selective p38 mitogen-activated protein kinase inhibitor, on functional capacity and cardiac function in patients with LMNA-related dilated cardiomyopathy. The results showed that ARRY-371797 was well tolerated and potentially increased functional capacity while lowering the concentration of the cardiac biomarker NT-proBNP.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Article
Genetics & Heredity
Marina C. Costa, Maria Calderon-Dominguez, Alipio Mangas, Oscar Campuzano, Georgia Sarquella-Brugada, Monica Ramos, Maribel Quezada-Feijoo, Jose Manuel Garcia Pinilla, Ainhoa Robles-Mezcua, Galan del Aguila Pacheco-Cruz, Thalia Belmonte, Francisco J. Enguita, Rocio Toro
Summary: Peripheral circRNAs show potential as non-invasive biomarkers for etiology-based diagnosis of dilated cardiomyopathy, with the ability to differentiate between different causes of DCM and correlate with echocardiographic parameters.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Cardiac & Cardiovascular Systems
Kseniya Perepelina, Anastasia Zaytseva, Aleksandr Khudiakov, Irina Neganova, Elena Vasichkina, Anna Malashicheva, Anna Kostareva
Summary: In this study, we successfully created an in vitro cardiac model of laminopathy using induced pluripotent stem cells from a patient carrying the LMNA p.R249Q genetic variant. Our findings demonstrate that this genetic variant leads to abnormal sodium currents in cardiomyocytes and alters the transcription levels of cardiac-specific genes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cell Biology
Yiming Wang, Hao Wu, Xiangxiang Jiang, Lei Jia, Meijiao Wang, Yin Rong, Shuo Chen, Yue Wang, Zhenyu Xiao, Xiaoyan Liang, Hongmei Wang
Summary: This study established human trophoblast stem cells (hTSCs) and revealed the molecular mechanisms underlying nuclear enlargement during trophoblast syncytialization. The findings highlight the significance of hTSCs as a model for understanding human trophoblast differentiation during implantation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Giada Cattelan, Laura Sophie Frommelt, Chiara Volani, Andrea Colliva, Giulio Ciucci, Alessia Paldino, Matteo Dal Ferro, Marina Di Segni, Rosamaria Silipigni, Peter P. Pramstaller, Marzia De Bortoli, Serena Zacchigna, Alessandra Rossini
Summary: In this study, a human induced pluripotent stem cell line was successfully created from peripheral blood mononuclear cells of a patient carrying a heterozygous LMNA variant. The cell line exhibited typical pluripotent cell morphology, normal karyotype, pluripotency markers, and the ability to differentiate into cardiomyocytes and endothelial cells. This cell line serves as an in vitro model to study the genetic basis of DCM.
STEM CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Kiran Hasygar, Onur Deniz, Ying Liu, Josef Gullmets, Riikka Hynynen, Hanna Ruhanen, Krista Kokki, Reijo Kakela, Ville Hietakangas
Summary: Energy storage and growth in animals are coordinated in response to nutrient status, with nutrient-regulated signaling pathways controlling these processes. ERK7 has been identified as an atypical MAP kinase inhibitor of adiposity and growth in Drosophila, with its mutant larvae showing increased lipid stores and accelerated growth. Moreover, ERK7 expression is elevated during fasting conditions, and ERK7 mutant larvae display impaired survival during nutrient deprivation.
Article
Chemistry, Multidisciplinary
Anne Skogberg, Sanna Siljander, Antti-Juhana Maki, Mari Honkanen, Alexander Efimov, Markus Hannula, Panu Lahtinen, Sampo Tuukkanen, Tomas Bjorkqvist, Pasi Kallio
Summary: A nanocellulose-based material with anisotropic conductivity is introduced, with a novel production method based on the alignment of cationic cellulose nanofibers at the dry-line boundary of an evaporating droplet.
Article
Biology
Martti Juhola, Henry Joutsijoki, Kirsi Penttinen, Disheet Shah, Risto-Pekka Polonen, Katriina Aalto-Setala
Summary: This research used machine learning algorithms to classify seven genetic cardiac diseases, achieving a best classification accuracy of approximately 69%. By measuring calcium transient signals from induced pluripotent stem cell-derived cardiomyocytes, 55 different machine learning methods were utilized.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Engineering, Electrical & Electronic
Martti Juhola, Henry Joutsijoki, Kirsi Penttinen, Disheet Shah, Katriina Aalto-Setala
Summary: This article discusses the data complexity of calcium transient signal data obtained from induced pluripotent stem cell-derived cardiomyocytes. It proposes a novel method to measure data complexity based on nearest neighbour searching. The study demonstrates that data complexity, which includes overlapping and mixed data classes and a large number of data cases, affects classification results. The data set used in the study consisted of genetic cardiovasular disease classes and healthy controls. Machine learning techniques, such as nearest neighbour searching, feedforward artificial neural networks, and random forests, were used to classify the data. Random forests produced the highest classification accuracy of 68% for all eight classes.
INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
(2022)
Article
Cell Biology
Gun West, Minttu Turunen, Anna Aalto, Laura Virtanen, Song-Ping Li, Tiina Helio, Annika Meinander, Pekka Taimen
Summary: This study reveals the intricate interplay between mutant lamins A and C and the protein degradation machinery. Mutant lamins A and C reduce the activity of the ubiquitin-proteasome system (UPS), leading to accumulation of K48-ubiquitin chains. However, compensatory enhanced autophagy can degrade the mutant lamins A and C. Furthermore, pharmacological interventions that enhance protein degradation can be beneficial for maintaining cellular homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Laura Virtanen, Emilia Holm, Mona Halme, Gun West, Fanny Lindholm, Josef Gullmets, Juho Irjala, Tiina Helio, Artur Padzik, Annika Meinander, John E. Eriksson, Pekka Taimen
Summary: The heat shock response is crucial for cell survival in harmful environments. This study found that lamin A/C, encoded by the LMNA gene, is reversibly phosphorylated at serine 22 upon heat shock, facilitating nucleoplasmic localization and nuclear shape changes. This phosphorylation stoichiometry of lamin A/C plays a conserved role in regulating lamina structure and promoting cell survival during heat shock.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Kirsi Penttinen, Chandra Prajapati, Disheet Shah, Dhanesh Kattipparambil Rajan, Reeja Maria Cherian, Heikki Swan, Katriina Aalto-Setala
Summary: Brugada syndrome is a genetic cardiac arrhythmia disorder associated with mutations in the SCN5A gene. This study aimed to observe phenotype-specific differences in hiPSC-derived CMs from symptomatic and asymptomatic mutation carriers.
BMC CARDIOVASCULAR DISORDERS
(2023)
Article
Cell & Tissue Engineering
Davi M. Lyra-Leite, Raymond R. Copley, Phillip P. Freeman, Praeploy Pongpamorn, Disheet Shah, Donald E. McKenna, Brian Lenny, Emily A. Pinheiro, Carly J. Weddle, Mennat Gharib, Hoor Javed, Hananeh Fonoudi, Yadav Sapkota, Paul W. Burridge
Summary: By simplifying the components of the basal medium, we have successfully improved the growth rate of hiPSCs and maintained their pluripotent state, which is crucial for hiPSC derivation and differentiation.
Review
Biochemistry & Molecular Biology
Abhimanyu Thakur, Disheet Shah, Deepika Rai, Diana Carolina Parra, Spoorthy Pathikonda, Svetlana Kurilova, Alma Cili
Summary: Exosomes, small extracellular nanovesicles released by cells, have shown potential for use in cosmetics, skin care, tissue regeneration, and dermatological diseases. Their therapeutic value lies in their ability to modulate the cell microenvironment, regulate gene expression, and induce cell differentiation for positive impacts on the skin. Exosomes have been used to reduce wrinkles, improve skin texture and hydration, enhance elasticity, reduce inflammation and UV damage, promote tissue regeneration, and treat various skin conditions.
Article
Multidisciplinary Sciences
Purnima Singh, Liting Zhou, Disheet A. Shah, Romina B. Cejas, David K. Crossman, Mariam Jouni, Tarek Magdy, Xuexia Wang, Noha Sharafeldin, Lindsey Hageman, Donald E. McKenna, Steve Horvath, Saro H. Armenian, Frank M. Balis, Douglas S. Hawkins, Frank G. Keller, Melissa M. Hudson, Joseph P. Neglia, A. Kim Ritchey, Jill P. Ginsberg, Wendy Landier, Paul W. Burridge, Smita Bhatia
Summary: Investigation found an association between genome-wide differential methylation at CpG sites in peripheral blood DNA and anthracycline-induced cardiomyopathy. Several genes associated with cardiac dysfunction were also identified. This suggests that differential DNA methylation of certain genes could play a role in the pathogenesis of anthracycline-induced cardiomyopathy.
SCIENTIFIC REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Purnima Singh, Disheet A. Shah, Mariam Jouni, Romina B. Cejas, David K. Crossman, Tarek Magdy, Shaowei Qiu, Xuexia Wang, Liting Zhou, Noha Sharafeldin, Lindsey Hageman, Donald E. McKenna, Saro H. Armenian, Frank M. Balis, Douglas S. Hawkins, Frank G. Keller, Melissa M. Hudson, Joseph P. Neglia, A. Kim Ritchey, Jill P. Ginsberg, Wendy Landier, Ravi Bhatia, Paul W. Burridge, Smita Bhatia
Summary: This study examined the differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. The results revealed dysregulation of several genes, including LDHA, CD36, IL1R1, IL1R2, MMP8, and MMP9, that are associated with metabolic perturbations, structural remodeling, and symptomatic cardiotoxicity in these survivors.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cell Biology
Gun West, Sogol Sedighi, Giulio Agnetti, Pekka Taimen
Summary: The intermediate filament cytoskeleton, composed of desmin and lamins, plays a crucial role in maintaining the structural integrity of the nucleus in cardiomyocytes. Mutations in these proteins can lead to cardiomyopathies, highlighting the importance of their synergistic roles in nuclear stability and mechanical signal transduction.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Disheet A. Shah, Yadav Sapkota, Paul W. Burridge
CIRCULATION RESEARCH
(2022)
