Article
Multidisciplinary Sciences
Yasuhide Kuwabara, Allen J. York, Suh-Chin Lin, Michelle A. Sargent, Kelly M. Grimes, James P. Pirruccello, Jeffery D. Molkentin
Summary: We identified a variant in the FLII gene that is associated with cardiac remodeling in heart disease. Further studies showed that Flii protein binds to sarcomeric actin thin filament and affects its length. Deletion of Flii or introduction of the R1245H amino acid substitution in mice resulted in cardiomyopathy due to shortening of actin thin filaments. The FLII variant increases the risk of cardiomyopathy by altering sarcomere structure and contractile dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Giuseppina Mastrototaro, Pierluigi Carullo, Jianlin Zhang, Beatrice Scellini, Nicoletta Piroddi, Simona Nemska, Maria Carmela Filomena, Simone Serio, Carol A. Otey, Chiara Tesi, Fabian Emrich, Wolfgang A. Linke, Corrado Poggesi, Simona Boncompagni, Marie-Louise Bang, Nuno Guimaraes-Camboa
Summary: Palladin (PALLD) is a protein associated with actin and immunoglobulin in the heart. Its role in the heart has been unclear due to embryonic lethality in knockout mice. However, a study found that PALLD is necessary for normal cardiac function, as its deletion in adult mice led to cardiac abnormalities and dysfunction. Additionally, PALLD interacts with other proteins such as CARP/Ankrd1 and FHOD1. This research sheds light on the importance of PALLD in the heart.
Review
Cardiac & Cardiovascular Systems
Christine M. Loescher, Anastasia J. Hobbach, Wolfgang A. Linke
Summary: This review provides an overview of the changes in cardiac titin properties at a molecular level, including the role isoform diversity and post-translational modifications play in regulating myocardial function, and discusses the importance of this regulation imbalance in heart disease.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Yuanyuan Dai, Nadezda Ignatyeva, Hang Xu, Ruheen Wali, Karl Toischer, Soeren Brandenburg, Christof Lenz, Julius Pronto, Funsho E. Fakuade, Samuel Sossalla, Elisabeth M. Zeisberg, Andreas Janshoff, Ingo Kutschka, Niels Voigt, Henning Urlaub, Torsten Bloch Rasmussen, Jens Mogensen, Stephan E. Lehnart, Gerd Hasenfuss, Antje Ebert
Summary: This study identified impaired subcellular iron uptake mechanisms in cardiomyocytes of heart failure patients, which are independent of systemic iron metabolism. The defects in clathrin-mediated endocytosis and cargo transfer were found to be responsible for subcellular iron deficiency in dilated cardiomyopathy. Restoring the molecular pathway through genetic correction, peptide treatment, or iron supplementation rescued the dysfunction and improved contractility, indicating a potential treatment strategy for heart failure.
CIRCULATION RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Paul H. Goldspink, Chad M. Warren, Jan Kitajewski, Beata M. Wolska, R. John Solaro
Summary: The dominant mechanism of sudden cardiac death in the young is the maladaptive responses to genes encoding proteins linked to hypertrophic cardiomyopathy, mostly mutant sarcomere proteins. These mutations impose a biophysical defect on myofilament tension generation, leading to disease progression. Personalized treatments are being explored based on advanced understanding of this progression.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Cell Biology
Sophie Broadway-Stringer, He Jiang, Kirsty Wadmore, Charlotte Hooper, Gillian Douglas, Violetta Steeples, Amar J. Azad, Evie Singer, Jasmeet S. Reyat, Frantisek Galatik, Elisabeth Ehler, Pauline Bennett, Jacinta I. Kalisch-Smith, Duncan B. Sparrow, Benjamin Davies, Kristina Djinovic-Carugo, Mathias Gautel, Hugh Watkins, Katja Gehmlich
Summary: Pathogenic variants in ACTN2 gene have been identified as rare causes of Hypertrophic Cardiomyopathy. However, the underlying disease mechanisms are not well understood. This study found that a missense variant in alpha-actinin renders the protein less stable, leading to molecular and morphological abnormalities in mouse hearts.
Article
Cardiac & Cardiovascular Systems
Shi Shen, Lorenzo R. Sewanan, Stuart G. Campbell
Summary: A novel in-vitro platform was created to study reverse remodeling of engineered heart tissue after mechanical unloading. The research found that stress-free tissue length increased after chronic stretch but gradually decreased back to its original value within 9 days, suggesting a role for actomyosin contraction in reverse remodeling. Additionally, active sarcomeric contraction and fibroblast activity were found to play essential roles in reverse remodeling of myocardium after mechanical unloading.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Thomas L. Lynch, Mohit Kumar, James W. McNamara, Diederik W. D. Kuster, Mayandi Sivaguru, Rohit R. Singh, Michael J. Previs, Kyoung Hwan Lee, Gina Kuffel, Michael J. Zilliox, Brian Leei Lin, Weikang Ma, Aaron M. Gibson, Burns C. Blaxall, Michelle L. Nieman, John N. Lorenz, Dana M. Leichter, Owen P. Leary, Paul M. L. Janssen, Pieter P. de Tombe, Richard J. Gilbert, Roger Craig, Thomas Irving, David M. Warshaw, Sakthivel Sadayappan
Summary: Phosphorylation and dephosphorylation of cardiac myosin binding protein-C play crucial roles in regulating cardiac contraction and actomyosin interactions. The amino terminus region of cMyBP-C is essential for maintaining normal cardiac structure and function, with its deletion resulting in dilated cardiomyopathy.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Anthony M. Pettinato, Feria A. Ladha, J. Travis Hinson
Summary: This article reviews the impact of the lack of adult human cardiomyocyte proliferative capacity on cardiac regeneration and summarizes the regulatory mechanisms connecting the human cardiomyocyte sarcomere to cell cycle regulation, aiming to enhance cardiac regeneration by reducing the inhibitory effects of the sarcomere.
CURRENT CARDIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
XiaoDong Jin, WenYe Liu, Jing Miao, ZhiPeng Tai, LingYa Li, PengPeng Guan, Jing-Xia Liu
Summary: The study shows that disrupted Cu2+ homeostasis can lead to developmental defects in zebrafish myogenesis, possibly through regulating gene promoter methylation and histone modification to affect signaling transduction pathways.
Review
Biochemistry & Molecular Biology
Ashley A. Martin, Brian R. Thompson, Dongwoo Hahn, Addeli Bez Batti Angulski, Nora Hosny, Houda Cohen, Joseph M. Metzger
Summary: This review emphasizes the signaling components and regulatory mechanisms that impact cardiac sarcomere function, with a focus on the roles of the thick and thin filaments. The emerging field of inter-myofilament signaling and its important mediators are also discussed. Additionally, recent methods for studying the sarcomere under intact, physiologically relevant conditions are reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biology
Seung-Hee Yoo
Summary: The circadian clock has a fundamental role in the physiology of the heart, particularly in regulating gene expression and protein degradation related to cardiac function. Recent studies have shown a circadian regulation of sarcomere integrity and function, suggesting it may be a key regulatory mechanism in cardiac remodeling. Therapeutic strategies targeting circadian control in the heart could greatly improve intervention outcomes against cardiovascular disease.
CHRONOBIOLOGY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Amy N. Adkins, Julius P. A. Dewald, Lindsay P. Garmirian, Christa M. Nelson, Wendy M. Murray
Summary: Muscle architecture is plastic and changes in input or use can alter its structure. Differences in serial sarcomere number and physiological cross-sectional area of the biceps brachii between stroke patients and healthy controls suggest muscle adaptations associated with stroke.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Wataru Miyake, Mayu Minemoto, Hiromasa Hayama, Masaya Yamamoto, Toru Okazaki, Kozue Takano, Kotaro Mori, Atsuko Okazaki, Reiko Arakawa, Hisao Hara, Fumihiko Takeuchi, Yukio Hiroi, Norihiro Kato
Summary: LVNC is a genetically and phenotypically heterogeneous heart muscle disorder, with two sporadic adult cases presenting acute heart failure and causal gene mutations. After treatment, morphological features and cardiac function gradually improved, indicating phenotypic plasticity or undulation of LVNC.
INTERNATIONAL HEART JOURNAL
(2021)
Article
Biology
Daniel Porto, Yohei Matsunaga, Barbara Franke, Rhys M. Williams, Hiroshi Qadota, Olga Mayans, Guy M. Benian, Hang Lu
Summary: The study demonstrates the stretch-unfolding of twitchin kinase in active muscle, with mechanical activity regulating the signaling pathway of this cytoskeletal kinase. The developed techniques could be used to obtain in vivo evidence for force-induced conformational changes or elastic behavior of other proteins.