Review
Biology
Carol Ann Remme
Summary: The influx of sodium ions through voltage-gated sodium channels is crucial for proper electrical conduction in the heart. Dysfunction of sodium channels can lead to life-threatening arrhythmias in acquired conditions and inherited disorders. Recent research has revealed the complex nature of sodium channel distribution and function, as well as its impact on cardiac structural integrity. Moreover, sodium channels and their role in various extracardiac tissues are being increasingly recognized. This review provides an overview of these novel insights and their contribution to our understanding of sodium channelopathies and dysfunction.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Physiology
Andras Varro, Jakub Tomek, Norbert Nagy, Laszlo Virag, Elisa Passini, Blanca Rodriguez, Istvan Baczko
Summary: Cardiac arrhythmias often stem from changes in the electro-physiological properties of cardiac cells and their ionic mechanisms. Understanding the pathophysiology of human cellular electrophysiology can aid in developing novel antiarrhythmic strategies.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Clinical Neurology
Ming S. Soh, Richard D. Bagnall, Christopher Semsarian, Ingrid E. Scheffer, Samuel F. Berkovic, Christopher A. Reid
Summary: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in epilepsy. This study found that SCN5A arrhythmogenic variants may confer increased risk of sudden death in individuals with epilepsy.
Article
Gastroenterology & Hepatology
Connor A. Emdin, Mary Haas, Veeral Ajmera, Tracey G. Simon, Julian Homburger, Cynthia Neben, Lan Jiang, Wei-Qi Wei, Qiping Feng, Alicia Zhou, Joshua Denny, Kathleen Corey, Rohit Loomba, Sekar Kathiresan, Amit Khera
Summary: This study identified 12 independent genetic variants, including 7 newly identified ones, that confer risk for cirrhosis. A polygenic score based on these variants can identify a subset of the population at substantially increased risk, particularly those susceptible to the hepatotoxic effects of excess alcohol consumption or obesity.
Article
Urology & Nephrology
Cassianne Robinson-Cohen, Jefferson L. Triozzi, Bryce Rowan, Jing He, Hua C. Chen, Neil S. Zheng, Wei-Qi Wei, Otis D. Wilson, Jacklyn N. Hellwege, Philip S. Tsao, J. Michael Gaziano, Alexander Bick, Michael E. Matheny, Cecilia P. Chung, Loren Lipworth, Edward D. Siew, T. Alp Ikizler, Ran Tao, Adriana M. Hung
Summary: By conducting a meta-analysis of genome-wide association studies, three genetic loci associated with longitudinal eGFR change have been identified, shedding light on the molecular mechanisms of eGFR decline and potentially contributing to the development of new therapeutic approaches for progressive CKD.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Urology & Nephrology
Cassianne Robinson-Cohen, Jefferson L. Triozzi, Bryce Rowan, Jing He, Hua C. Chen, Neil S. Zheng, Wei-Qi Wei, Otis D. Wilson, Jacklyn N. Hellwege, Philip S. Tsao, J. Michael Gaziano, Alexander Bick, Michael E. Matheny, Cecilia P. Chung, Loren Lipworth, Edward D. Siew, T. Alp Ikizler, Ran Tao, Adriana M. Hung
Summary: The study identified three significant loci associated with longitudinal decline in eGFR, providing insights into the molecular mechanisms of eGFR decline and potential therapeutic approaches for progressive CKD.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Physiology
Vamsi Krishna Murthy Ginjupalli, Michael Cupelli, Jean-Baptiste Reisqs, Yvonne Sleiman, Nabil El-Sherif, Genevieve Gourdon, Jack Puymirat, Mohamed Chahine, Mohamed Boutjdir
Summary: Myotonic dystrophy type 1 (DM1) is a genetic disorder that causes conduction abnormalities and arrhythmias in the heart. This study found that in a mouse model of DM1, there were reduced densities of sodium current, L-type calcium current, and transient outward potassium current, as well as changes in gating properties of L-type calcium channels, which may contribute to the observed ECG abnormalities. These findings suggest potential targeted therapeutics for DM1.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Genetics & Heredity
Oliver Bundgaard Vad, Yannan Yan, Federico Denti, Gustav Ahlberg, Lena Refsgaard, Sofia Hammami Bomholtz, Joana Larupa Santos, Simon Rasmussen, Stig Haunso, Jesper Hastrup Svendsen, Ingrid Elizabeth Christophersen, Nicole Schmitt, Morten Salling Olesen, Bo Hjorth Bentzen
Summary: AF is a common sustained cardiac arrhythmia with complex pathogenesis, and rare genetic variants in the CACNA1A gene have been identified in patients with familial AF, suggesting a potential novel link between ion channel dysfunction and increased risk of AF.
FRONTIERS IN GENETICS
(2022)
Article
Clinical Neurology
Manuela M. X. Tan, Michael A. Lawton, Edwin Jabbari, Regina H. Reynolds, Hirotaka Iwaki, Cornelis Blauwendraat, Sofia Kanavou, Miriam Pollard, Leon Hubbard, Naveed Malek, Katherine A. Grosset, Sarah L. Marrinan, Nin Bajaj, Roger A. Barker, David J. Burn, Catherine Bresner, Thomas Foltynie, Nicholas W. Wood, Caroline H. Williams-Gray, John Hardy, Michael A. Nalls, Andrew B. Singleton, Nigel M. Williams, Yoav Ben-Shlomo, Michele T. M. Hu, Donald G. Grosset, Maryam Shoai, Huw R. Morris
Summary: The study found that genetic variants associated with Parkinson's disease risk are not linked to disease progression. The APOE epsilon 4 tagging variant was significantly associated with cognitive progression, while ATP8B2 gene showed a nominal association with motor progression. The new method shows promise in improving the measurement of symptom progression in PD.
MOVEMENT DISORDERS
(2021)
Article
Multidisciplinary Sciences
Mina-A Jhun, Michael Mendelson, Rory Wilson, Rahul Gondalia, Roby Joehanes, Elias Salfati, Xiaoping Zhao, Kim Valeska Emilie Braun, Anh Nguyet Do, Asa K. Hedman, Tao Zhang, Elena Carnero-Montoro, Jincheng Shen, Traci M. Bartz, Jennifer A. Brody, May E. Montasser, Jeff R. O'Connell, Chen Yao, Rui Xia, Eric Boerwinkle, Megan Grove, Weihua Guan, Pfeiffer Liliane, Paula Singmann, Martina Mueller-Nurasyid, Thomas Meitinger, Christian Gieger, Annette Peters, Wei Zhao, Erin B. Ware, Jennifer A. Smith, Klodian Dhana, Joyce van Meurs, Andre Uitterlinden, Mohammad Arfan Ikram, Mohsen Ghanbari, Deugi Zhi, Stefan Gustafsson, Lars Lind, Shengxu Li, Dianjianyi Sun, Tim D. Spector, Yii-der Ida Chen, Coleen Damcott, Alan R. Shuldiner, Devin M. Absher, Steve Horvath, Philip S. Tsao, Sharon Kardia, Bruce M. Psaty, Nona Sotoodehnia, Jordana T. Bell, Erik Ingelsson, Wei Chen, Abbas Dehghan, Donna K. Arnett, Melanie Waldenberger, Lifang Hou, Eric A. Whitsel, Andrea Baccarelli, Daniel Levy, Myriam Fornage, Marguerite R. Irvin, Themistocles L. Assimes
Summary: The study reveals strong and consistent associations between DNA methylation and blood lipid levels across multiple racial/ethnic groups, with specific and common CpG-lipid trait associations identified through a large-scale multi-ethnic epigenome-wide association study.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Carina Mauersberger, Heribert Schunkert, Hendrik B. Sager
Summary: While the importance of inflammation in atherosclerosis is recognized, the exact molecular processes remain unclear. Modern genetics, specifically genome-wide association studies, have revealed many loci related to inflammatory processes in coronary artery disease, but translating these findings into specific molecular mechanisms is still challenging.
Article
Urology & Nephrology
Xu-Jie Zhou, Tao Su, Jingyuan Xie, Qiong-Hong Xie, Li-Zhong Wang, Yong Hu, Gang Chen, Yan Jia, Jun-Wen Huang, Gui Li, Yang Liu, Xiao-Juan Yu, Swapan K. Nath, Lam C. Tsoi, Matthew T. Patrick, Celine C. Berthier, Gang Liu, Su-Xia Wang, Huji Xu, Nan Chen, Chuan-Ming Hao, Hong Zhang, Li Yang
Summary: This study identified two candidate genome regions associated with susceptibility to acute tubulointerstitial nephritis (ATIN), suggesting a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Obstetrics & Gynecology
Hamdi Mbarek, Scott D. Gordon, David L. Duffy, Nikki Hubers, Sally Mortlock, Jeffrey J. Beck, Jouke-Jan Hottenga, Rene Pool, Conor Dolan, Ky'Era Actkins, Zachary F. Gerring, Jenny Van Dongen, Erik A. Ehli, William G. Iacono, Matt Mcgue, Daniel Chasman, C. Scott Gallagher, Samantha L. P. Schilit, Cynthia C. Morton, Guillaume Pare, Gonneke Willemsen, David C. Whiteman, Catherine M. Olsen, Catherine Derom, Robert Vlietinck, Daniel Gudbjartsson, Lisa Cannon-Albright, Eva Krapohl, Robert Plomin, Patrik K. E. Magnusson, Nancy L. Pedersen, Pirro Hysi, Massimo Mangino, Timothy D. Spector, Teemu Palviainen, Yuri Milaneschi, Brenda W. Penninnx, Adrian Campos, Ken K. Ong, John R. B. Perry, Cornelis B. Lambalk, Jaakko Kaprio, Isleifur Olafsson, Karine Duroure, Celine Revenu, Miguel E. Renteria, Loic Yengo, Lea Davis, Eske M. Derks, Sarah E. Medland, Hreinn Stefansson, Kari Stefansson, Filippo Del Bene, Bruno Reversade, Grant W. Montgomery, Dorret Boomsma, Nicholas G. Martin
Summary: This study identified four new loci associated with female propensity for giving birth to spontaneous dizygotic twins. The novel loci, GNRH1 and FSHR, have established roles in female reproduction, while ZFPM1 and IPO8 were not previously linked to female fertility. The study also found significant genetic correlations with multiple aspects of female reproduction and body size, suggesting important roles in human evolution.
HUMAN REPRODUCTION
(2023)
Article
Hematology
Paola Leon-Mimila, Hugo Villamil-Ramirez, Luis R. Macias-Kauffer, Leonor Jacobo-Albavera, Blanca E. Lopez-Contreras, Rosalinda Posadas-Sanchez, Carlos Posadas-Romero, Sandra Romero-Hidalgo, Sofia Moran-Ramos, Mayra Dominguez-Perez, Marisol Olivares-Arevalo, Priscilla Lopez-Montoya, Roberto Nieto-Guerra, Victor Acuna-Alonzo, Gaston Macin-Perez, Rodrigo Barquera-Lozano, Blanca E. Del-Rio-Navarro, Israel Gonzalez-Gonzalez, Francisco Campos-Perez, Francisco Gomez-Perez, Victor J. Valdes, Alicia Sampieri, Juan G. Reyes-Garcia, Miriam Del C. Carrasco-Portugal, Francisco J. Flores-Murrieta, Carlos A. Aguilar-Salinas, Gilberto Vargas-Alarcon, Diana Shih, Peter J. Meikle, Anna C. Calkin, Brian G. Drew, Luis Vaca, Aldons J. Lusis, Adriana Huertas-Vazquez, Teresa Villarreal-Molina, Samuel Canizales-Quinteros
Summary: The study identified a genetic variant in the SIDT2 gene associated with HDL-C levels and cardiovascular risk in Mexicans, with implications for cholesterol and lipoprotein metabolism. The SIDT2/Val636Ile variant was more common in Native American populations and linked to lower LDL-C and ApoB levels. Further investigation showed that the variant affects cholesterol transport function, highlighting SIDT2 as a new player in human lipid metabolism.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Tejas P. Singh, Matt A. Field, Matthew J. Bown, Gregory T. Jones, Jonathan Golledge
Summary: This study systematically reviewed previous AAA GWAS and identified 33 SNPs associated with AAA diagnosis at genome-wide significance. However, the association between SNPs and AAA growth was not adequately examined. Previous GWAS have various design limitations, such as inconsistent case and control ascertainment and limited phenotyping of the AAAs.
Article
Medicine, Legal
Ivan Gando, Nori Williams, Glenn Fishman, Barbara A. Sampson, Yingying Tan, William A. Coetzee
FORENSIC SCIENCE INTERNATIONAL
(2019)
Article
Endocrinology & Metabolism
Anne R. Cappola, Akshay S. Desai, Marco Medici, Lawton S. Cooper, Debra Egan, George Sopko, Glenn I. Fishman, Steven Goldman, David S. Cooper, Samia Mora, Peter J. Kudenchuk, Anthony N. Hollenberg, Cheryl L. McDonald, Paul W. Ladenson
Article
Cardiac & Cardiovascular Systems
Anne R. Cappola, Akshay S. Desai, Marco Medici, Lawton S. Cooper, Debra Egan, George Sopko, Glenn I. Fishman, Steven Goldman, David S. Cooper, Samia Mora, Peter J. Kudenchuk, Anthony N. Hollenberg, Cheryl L. McDonald, Paul W. Ladenson
Article
Medicine, Research & Experimental
Eric Himelman, Mauricio A. Lillo, Julie Nouet, J. Patrick Gonzalez, Qingshi Zhao, Lai-Hua Xie, Hong Li, Tong Liu, Xander Ht Wehrens, Paul D. Lampe, Glenn Fishman, Natalia Shirokova, Jorge E. Contreras, Diego Fraidenraich
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Medicine, General & Internal
Harmony R. Reynolds, Samrachana Adhikari, Claudia Pulgarin, Andrea B. Troxel, Eduardo Iturrate, Stephen B. Johnson, Anais Hausvater, Jonathan D. Newman, Jeffrey S. Berger, Sripal Bangalore, Stuart D. Katz, Glenn I. Fishman, Dennis Kunichoff, Yu Chen, Gbenga Ogedegbe, Judith S. Hochman
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Letter
Medicine, General & Internal
Sripal Bangalore, Atul Sharma, Alexander Slotwiner
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Review
Hematology
Bernard S. Kadosh, Michael S. Garshick, Juan Gaztanaga, Kathryn J. Moore, Jonathan D. Newman, Michael Pillinger, Ravichandran Ramasamy, Harmony R. Reynolds, Binita Shah, Judith Hochman, Glenn Fishman, Stuart D. Katz
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2020)
Editorial Material
Cardiac & Cardiovascular Systems
David S. Park, Glenn I. Fishman
CIRCULATION RESEARCH
(2020)
Article
Cardiac & Cardiovascular Systems
David S. Park, Akshay Shekhar, John Santucci, Gabriel Redel-Traub, Sergio Solinas, Shana Mintz, Xianming Lin, Ernest Whanwook Chang, Deven Narke, Yuhe Xia, Mitchell Goldfarb, Glenn I. Fishman
CIRCULATION RESEARCH
(2020)
Letter
Cardiac & Cardiovascular Systems
Nathaniel R. Smilowitz, Neil Jethani, Ji Chen, Yindalon Aphinyanaphongs, Ruina Zhang, Siddhant Dogra, Carlos L. Alviar, Norma Keller, Louai Razzouk, Adriana Quinones-Camacho, Albert S. Jung, Glenn I. Fishman, Judith S. Hochman, Jeffrey S. Berger
Letter
Cardiac & Cardiovascular Systems
Nathaniel R. Smilowitz, Vuthy Nguy, Yindalon Aphinyanaphongs, Jonathan D. Newman, Yuhe Xia, Harmony R. Reynolds, Judith S. Hochman, Glenn I. Fishman, Jeffrey S. Berger
Article
Acoustics
Akshay Shekhar, Orlando Aristizabal, Glenn I. Fishman, Colin K. L. Phoon, Jeffrey A. Ketterling
Summary: An ultrasound vector-flow workflow was used to visualize and quantify the complex hemodynamics within the mouse heart. Fhf2(WT/Y) mice showed repeatable cardiac function at all temperatures, while Fhf2(KO/Y) mice displayed dyssynchronous contractile motion that disrupted normal inflow vortex formation and impaired left ventricular filling as temperature rose. The hexplex processing approach demonstrated the ability to visualize and quantify the interplay between hemodynamic and mechanical function in a mouse model of human CVD.
IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
(2021)
Article
Developmental Biology
Camila Delgado, Lei Bu, Jie Zhang, Fang-Yu Liu, Joseph Sall, Feng-Xia Liang, Andrew J. Furley, Glenn Fishman
Summary: The study identified highly enriched IgSF-CAMs in the ventricular conduction system, such as CNTN2, NCAM-1, and ALCAM, which showed dynamic expression patterns during PC development. Deficiency in NCAM-1 resulted in defects in PC gene expression, VCS patterning, and cardiac conduction disease. The research also revealed that post-translational modification of NCAM-1 plays a role in sarcolemmal protein trafficking and extracellular space expansion between apposing PCs.
Article
Clinical Neurology
Jana Veliskova, Christopher Marra, Yue Liu, Akshay Shekhar, David S. Park, Vasilisa Iatckova, Ying Xie, Glenn I. Fishman, Libor Velisek, Mitchell Goldfarb
Summary: The Arg52His mutation in the FHF1 gene leads to severe seizures and sudden death in mice, with abnormal heart rhythm suggesting a functional axis between FHF1 and Na(v)1.6 underlying changes in brain sodium channel gating in epileptic encephalopathy.
Article
Endocrinology & Metabolism
Juan Gaztanaga, Ravichandran Ramasamy, Ann Marie Schmidt, Glenn Fishman, Shoshana Schendelman, Karthinathan Thangavelu, Riccardo Perfetti, Stuart D. Katz
Summary: The study demonstrated that treatment with AT-001 was safe and well tolerated in hospitalized COVID-19 patients with comorbid diabetes mellitus and heart disease. There was a trend towards reduced mortality and shortened length of hospital stay in the AT-001 group compared to two matched control groups.
DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS
(2021)
