Article
Biochemistry & Molecular Biology
Saraswathi Ponnam, Thomas Kampourakis
Summary: The study reveals that cMyBP-C regulates the function of cardiac myosin by interacting with different regions of the myosin molecule. The N-terminal domains of cMyBP-C interact with the head and tail domains of myosin through phosphorylation-independent and phosphorylation-dependent interactions, while the highest affinity interaction sites between cMyBP-C and myosin S1 are located in the central domains.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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)
Article
Cardiac & Cardiovascular Systems
Xiaoxu Zhou, Euy-Myoung Jeong, Hong Liu, Bahaa Kaseer, Man Liu, Suvash Shrestha, Hafiz Imran, Kylie Kavanagh, Ning Jiang, Lori-Ann Desimone, Feng Feng, Guangbin Shi, Go Eun Jeong, Anyu Zhou, Philip Stockwell, Samuel C. Dudley
Summary: This study found that circulating S-glutathionylated cMyBP-C was elevated in humans, monkeys, and mice with diastolic dysfunction (DD), suggesting that it may serve as a novel biomarker for the presence of DD.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cell Biology
Athiththan Yogeswaran, Christian Troidl, James W. McNamara, Jochen Wilhelm, Theresa Truschel, Laila Widmann, Muhammad Aslam, Christian W. Hamm, Sakthivel Sadayappan, Christoph Lipps
Summary: C0-C1f induces inflammatory responses in human fibroblasts and activates macrophages, which can be counteracted by TGF beta signaling. Specific targeting of the TLR4 signaling pathway may be an innovative strategy to modulate C0-C1f-mediated inflammation.
Article
Multidisciplinary Sciences
Taejeong Song, James W. McNamara, Weikang Ma, Maicon Landim-Vieira, Kyoung Hwan Lee, Lisa A. Martin, Judith A. Heiny, John N. Lorenz, Roger Craig, Jose Renato Pinto, Thomas Irving, Sakthivel Sadayappan
Summary: The study found that knockout mice lacking the fMyBP-C gene showed significant changes in muscle structure and function, such as decreased grip strength and muscle force, less ordered myosin heads, increased interfilament lattice spacing, and reduced calcium sensitivity. This indicates that fMyBP-C plays a critical role in muscle contraction speed and force, sarcomere integrity, and calcium sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Kelsey H. Collins, Chang Gui, Erica Ely, Kristin L. Lenz, Charles A. Harris, Farshid Guilak, Gretchen A. Meyer
Summary: The study demonstrates the essential role of adipose tissue in the development of normal muscle mass and strength. The adipokine leptin is found to be critical in rescuing the deficits in mass and contractile tension. This finding expands our understanding of adipokines in muscle homeostasis.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Biochemistry & Molecular Biology
Carmen Suay-Corredera, Jorge Alegre-Cebollada
Summary: Hypertrophic cardiomyopathy (HCM) is the most common inherited disorder of the heart, characterized by cardiac muscle hypertrophy and hypercontractility. This review summarizes the clinical and genetic aspects of HCM and provides updated information on therapeutic options targeting sarcomere mechanical activity. The authors also discuss the correlation between altered mechanical properties of cMyBP-C and HCM development.
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)
Article
Multidisciplinary Sciences
Cristina M. Risi, Ian Pepper, Betty Belknap, Maicon Landim-Vieira, Howard D. White, Kelly Dryden, Jose R. Pinto, P. Bryant Chase, Vitold E. Galkin
Summary: The study reveals the structural composition of cardiac thin filaments under systolic Ca2+ levels, showing that the two strands of the thin filament consist of troponin complexes with different binding states and short-range cooperativity. These findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, Research & Experimental
Lilei Zhang, Mukesh K. Jain
Summary: The circadian rhythm allows organisms to coordinate physiological functions in anticipation of environmental changes. The disruption of this rhythm leads to cardiometabolic disorders, affecting not only shift workers but also most individuals in modern society. Understanding circadian biology in cardiac metabolism is essential for developing novel chronotherapeutic strategies.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Pharmacology & Pharmacy
Yang Lee, Scott D. Zawieja, Mariappan Muthuchamy
Summary: The impact of obesity and metabolic syndrome on lymphatic function is an emerging field in research. Studies have shown consistent findings of lymphatic collecting vessel dysfunction in various metabolic disease models and organisms, and restoring lymphatic function can ameliorate obesity and insulin resistance. However, there is still much unknown about the mechanisms of lymphatic collecting vessel function in humans.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Carmen Suay-Corredera, Maria Rosaria Pricolo, Diana Velazquez-Carreras, Divya Pathak, Neha Nandwani, Carolina Pimenta-Lopes, David Sanchez-Ortiz, Inigo Urrutia-Irazabal, Silvia Vilches, Fernando Dominguez, Giulia Frisso, Lorenzo Monserrat, Pablo Garcia-Pavia, David de Sancho, James A. Spudich, Kathleen M. Ruppel, Elias Herrero-Galan, Jorge Alegre-Cebollada
Summary: Hypertrophic cardiomyopathy (HCM) is a disease caused by mutations in sarcomeric proteins, with many mutations not affecting protein structure or stability. Research shows that these mutations may disrupt the nanomechanics of cMyBP-C, affecting its regulatory role in actomyosin filaments.
Article
Multidisciplinary Sciences
Kirin D. Gada, Mengmeng Chang, Aishwarya Chandrashekar, Leigh D. Plant, Sami F. Noujaim, Diomedes E. Logothetis
Summary: G-protein-gated inwardly rectifying potassium (GIRK) channel activity is regulated by phosphatidylinositol-4,5-bisphosphate (PI 4,5P(2)), and PKC epsilon plays a role in the activation of GIRK channels in cardiac atrial cells and human stem cell-derived atrial cardiomyocytes. PKC epsilon enhances the interaction between GIRK4 and GIRK1/4 with PIP2, leading to increased channel activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Fabian Montecino, Natalia Gonzalez, Natasha Blanco, Manuel J. Ramirez, Adrian Gonzalez-Martin, Alejandra R. Alvarez, Hugo Olguin
Summary: The study reveals the role of c-Abl in regulating myogenic progression in satellite cells (SCs) by controlling Pax7 function and expression, affecting the activity and muscle regeneration of SCs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Physiology
Walter C. Thompson, Paul H. Goldspink
Summary: This review focuses on the crucial role of 14-3-3 proteins in regulating excitation-contraction coupling in muscle, highlighting the need for further investigation into their mechanistic actions in force generation.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Review
Oncology
Mohit Kumar, Chellappagounder Thangavel, Richard C. Becker, Sakthivel Sadayappan
Summary: Immunotherapy has significantly improved cancer treatment over the past two decades, but can also lead to immune-related adverse events, including cardiac toxicity. Reliable models are necessary for evaluating efficacy and safety, while innovative experimental systems can help identify biomarkers of immunotherapy-induced cardiotoxicity and lead to the discovery of new non-toxic immunotherapies.
Article
Physiology
Sheema Rahmanseresht, Kyoung H. Lee, Thomas S. O'Leary, James W. McNamara, Sakthivel Sadayappan, Jeffrey Robbins, David M. Warshaw, Roger Craig, Michael J. Previs
Summary: MyBP-C is a rod-like protein located within the sarcomere that interacts with actin and myosin. Super-resolution fluorescence microscopy shows that the N-terminal of MyBP-C is biased towards actin filaments in both active and relaxed muscle, potentially tuning cardiac contractility by capturing molecular binding partners.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Cell Biology
Sholeh Bazrafshan, Hani Kushlaf, Mashhood Kakroo, John Quinlan, Richard C. Becker, Sakthivel Sadayappan
Summary: This study reviewed electronic medical records of 651 patients with neuromuscular disorders and identified novel genetic variants associated with cardiac abnormalities in eight patients with muscular dystrophy. Further investigation is needed to better understand the relationship between cardiac disease features and genetic mutations in patients with neuromuscular disorders.
Article
Multidisciplinary Sciences
Taejeong Song, James W. McNamara, Weikang Ma, Maicon Landim-Vieira, Kyoung Hwan Lee, Lisa A. Martin, Judith A. Heiny, John N. Lorenz, Roger Craig, Jose Renato Pinto, Thomas Irving, Sakthivel Sadayappan
Summary: The study found that knockout mice lacking the fMyBP-C gene showed significant changes in muscle structure and function, such as decreased grip strength and muscle force, less ordered myosin heads, increased interfilament lattice spacing, and reduced calcium sensitivity. This indicates that fMyBP-C plays a critical role in muscle contraction speed and force, sarcomere integrity, and calcium sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Mohammed Arif, Perwez Alam, Rafeeq P. H. Ahmed, Raghav Pandey, Hafeez M. Faridi, Sakthivel Sadayappan
Summary: The study found that upregulated angiogenesis mediated by miR-210 is not sufficient to rescue the DCM phenotype in mice, despite significant increases in blood vessel density and upregulation of proangiogenic molecules observed in the hearts of TMx210 and 210-TG mice.
Article
Biochemistry & Molecular Biology
Rohit R. Singh, James W. McNamara, Sakthivel Sadayappan
Summary: This study investigates how mutations in S2 related to Hypertrophic Cardiomyopathy (HCM) disrupt the interaction with C0-C2, leading to the disease. Results show that mutant S2 proteins had reduced binding with C0C2 and exhibited higher affinity for PKA-treated proteins. Additionally, mutant S2 did not affect the rate of force redevelopment in skinned papillary muscle fibers, indicating alteration in actomyosin cross-bridge kinetics.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Athiththan Yogeswaran, Christian Troidl, James W. McNamara, Jochen Wilhelm, Theresa Truschel, Laila Widmann, Muhammad Aslam, Christian W. Hamm, Sakthivel Sadayappan, Christoph Lipps
Summary: C0-C1f induces inflammatory responses in human fibroblasts and activates macrophages, which can be counteracted by TGF beta signaling. Specific targeting of the TLR4 signaling pathway may be an innovative strategy to modulate C0-C1f-mediated inflammation.
Article
Health Care Sciences & Services
Kobra Haghighi, George Gardner, Elizabeth Vafiadaki, Mohit Kumar, Lisa C. Green, Jianyong Ma, Jeffrey S. Crocker, Sheryl Koch, Demetrios A. Arvanitis, Phillip Bidwell, Jack Rubinstein, Rutger van de Leur, Pieter A. Doevendans, Fadi G. Akar, Michael Tranter, Hong-Sheng Wang, Sakthivel Sadayappan, Deeptankar DeMazumder, Despina Sanoudou, Roger J. Hajjar, Francesca Stillitano, Evangelia G. Kranias
Summary: Study found that R14del-PLN mice exhibited atrioventricular conduction impairment and RV-specific calcium defects under stress conditions, similar to the electrocardiographic features seen in R14del-PLN patients. This suggests an urgent need to improve risk stratification in asymptomatic carriers to prevent fatal arrhythmias and delay cardiomyopathy onset.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Justin G. Boyer, Jiuzhou Huo, Sarah Han, Julian R. Havens, Vikram Prasad, Brian L. Lin, David A. Kass, Taejeong Song, Sakthivel Sadayappan, Ramzi J. Khairallah, Christopher W. Ward, Jeffery D. Molkentin
Summary: Satellite cells play a crucial role in the progression of muscular dystrophy, and their depletion can improve the pathology and muscle performance in dystrophic mouse models. Mechanistically, satellite cells initiate the expression of MyoD, which induces the re-expression of fetal genes in myofibers, leading to sarcolemmal destabilization. These findings suggest that satellite cell activation and the fetal gene program are maladaptive in chronic muscular dystrophy.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Jared M. McLendon, Xiaoming Zhang, Daniel S. Matasic, Mohit Kumar, Olha M. Koval, Isabella M. Grumbach, Sakthivel Sadayappan, Barry London, Ryan L. Boudreau
Summary: This study explores the dysregulation of Sorbs2 in adult-onset cardiomyopathies and heart failure. It demonstrates that Sorbs2 is crucial for maintaining structural integrity in cardiomyocytes and its loss leads to cardiac structural changes and contractile dysfunction. The study also identifies genetic variants associated with decreased Sorbs2 expression and human cardiac phenotypes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Biographical-Item
Cardiac & Cardiovascular Systems
Sakthivel Sadayappan, Evangelia G. Kranias
CIRCULATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Mohit Kumar, Kobra Haghighi, Sheryl Koch, Jack Rubinstein, Francesca Stillitano, Roger J. Hajjar, Evangelia G. Kranias, Sakthivel Sadayappan
Summary: Phospholamban gene mutations, particularly the deletion of Arginine 14 (R14del), can cause inherited cardiomyopathies characterized by arrhythmias and early death. In mutant mice with R14del-PLN, there is decreased contractile force and increased myofilament sensitivity to calcium in the right ventricle. However, treatment with the myosin activator omecamtiv mecarbil can reverse these effects and improve contractile parameters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Shane Nelson, Samantha Beck-Previs, Sakthivel Sadayappan, Carl Tong, David M. Warshaw
Summary: Striated muscle is regulated by the super-relaxed state (SRX) of myosin, and the turnover of ATP molecules in cardiac sarcomeres provides insights into the spatial arrangement and regulation of SRX myosin by myosin-binding protein C. The SRX state plays a central role in the metabolic and functional regulation of striated muscle.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Engineering, Biomedical
Sunder Neelakantan, Mohit Kumar, Emilio A. Mendiola, Haley Phelan, Vahid Serpooshan, Sakthivel Sadayappan, Reza Avazmohammadi
Summary: This study investigates the contractile behavior of the myocardium at multiple length scales in small animals. The results indicate that the contraction of the myocardium is dependent on transmural depth and relaxes faster in the direction with larger peak stresses.
ACTA BIOMATERIALIA
(2023)
Article
Physiology
Weikang Ma, Kyoung Hwan Lee, Christine E. Delligatti, M. Therese Davis, Yahan Zheng, Henry Gong, Jonathan A. Kirk, Roger Craig, Thomas Irving
Summary: Our study validates the use of liquid nitrogen-frozen and cryostored porcine myocardium as a test bed for biophysical studies of cardiac muscle, which can lead to consistent results with reduced animal usage. These studies are important for understanding the physiological and pathological aspects of heart muscle. Liquid nitrogen preservation is a practical approach for structural and functional studies of myocardium.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)