Review
Cell Biology
Patrick Ernst, Philip A. A. Bidwell, Michaela Dora, David D. D. Thomas, Forum Kamdar
Summary: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are an important technological advancement in cardiovascular research, providing a renewable source of human cardiomyocytes for various applications. They offer unique insights into human physiology and pathophysiology, particularly in studying calcium regulation in the context of cardiovascular disease. However, the relative immaturity of hiPSC-CMs compared to adult cardiomyocytes remains a limitation, and efforts are being made to improve their maturity. This review provides a comprehensive overview of cardiomyocyte calcium cycling and hiPSC technology, focusing on our current understanding of calcium in hiPSC-CMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biology
Xin Shen, Jonas van den Brink, Anna Bergan-Dahl, Terje R. Kolstad, Einar S. Norden, Yufeng Hou, Martin Laasmaa, Yuriana Aguilar-Sanchez, Ann P. Quick, Emil K. S. Espe, Ivar Sjaastad, Xander H. T. Wehrens, Andrew G. Edwards, Christian Soeller, William E. Louch
Summary: This study investigates the promotion of RyR cluster dispersion by prolonged beta-adrenergic stimulation in heart failure, and examines the underlying mechanisms. The findings demonstrate the intimate connection between RyR localization and function through channel phosphorylation by CaMKII and PKA, which plays a protective role in healthy cardiomyocytes but contributes to impaired cardiac function during heart failure.
Article
Engineering, Chemical
Yuhei Ogura, Hiroaki Ito, Shukei Sugita, Masanori Nakamura, Yoshihiro Ujihara
Summary: Mammals and birds have faster heart rates, and birds achieve fast Ca2+ concentration changes by increasing the Ca2+ removal capacity in the central part of the cardiomyocytes.
Review
Developmental Biology
Anna Kirillova, Lu Han, Honghai Liu, Bernhard Kuhn
Summary: Terminally differentiated cardiomyocytes are usually polyploid, limiting cell proliferation and cardiac regeneration. Mechanisms generating bi- and multi-nucleated cardiomyocytes, as well as polyploid nuclei, have been studied.
Review
Biochemistry & Molecular Biology
Sofia Beghi, Malgorzata Furmanik, Armand Jaminon, Rogier Veltrop, Nikolas Rapp, Kanin Wichapong, Elham Bidar, Annamaria Buschini, Leon J. Schurgers
Summary: Cardiovascular disease remains a major cause of death worldwide, despite advancements in medication and preventive measures. Calcium plays a vital role in the cardiovascular system, regulating events from action potentials to muscle contraction. Calcium calmodulin pathways are involved in the regulation of cardiac functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Tomi Tuomainen, Nikolay Naumenko, Maija Mutikainen, Anastasia Shakirzyanova, Sarah Sczelecki, Jennifer L. Estall, Jorge L. Ruas, Pasi Tavi
Summary: Non-canonical isoforms of PGC-1 alpha are expressed in the heart and can induce specific cardiac phenotypes through cellular signaling pathways. These findings reveal the different biological roles of PGC-1 alpha isoforms, which should be taken into account in future therapeutic developments.
Review
Engineering, Biomedical
Jinglin Wang, Xiangyi Wu, Junqi Zhao, Haozhen Ren, Yuanjin Zhao
Summary: This review comprehensively summarizes biomimetic liver microphysiological systems (MPSs), including their cellular composition, biomedical applications, challenges, and future development prospects. It introduces the key components of liver MPSs and their biomedical applications in disease modeling, drug metabolism, and toxicity testing. It also discusses the challenges faced by MPSs and proposes future research directions.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Dermatology
Austin Ambur, Asma Zaidi, Charles Dunn, Rajiv Nathoo
Summary: Darier disease is a skin disorder caused by mutations in the ATP2A2 gene. Patients often have associated neuropsychiatric disorders such as intellectual disability, bipolar disorder, schizophrenia, and suicidality. However, there is limited research on the pathophysiological mechanisms underlying these conditions.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zenghua Qi, Tao Wang, Xiangmao Chen, Chun Kit Wong, Qianqian Ding, Heinrich Sauer, Zhi-Feng Chen, Cheng Long, Xiaoqiang Yao, Zongwei Cai, Suk Ying Tsang
Summary: This study revealed the presence of intracellular Angiotensin II (iAng II) and its regulation of the automaticity of early differentiating cardiomyocytes via the AT(2)R and ryanodine receptor pathways. This provides evidence for the role of iAng II in regulating ESC-CMs behavior and fate determination.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
David E. Ebeid, Farid G. Khalafalla, Kathleen M. Broughton, Megan M. Monsanto, Carolina Y. Esquer, Veronica Sacchi, Nirmala Hariharan, Kelli Korski, Maryam Moshref, Jacqueline Emathinger, Christopher T. Cottage, Pearl J. Quijada, Jonathan H. Nguyen, Roberto Alvarez, Mirko Volkers, Mathias H. Konstandin, Bingyan J. Wang, Fareheh Firouzi, Julian M. Navarrete, Natalie A. Gude, Marie-Jose Goumans, Mark A. Sussman
Summary: Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGF beta pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase.
CARDIOVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Catrin F. Williams, Catherine Hather, Jainaba Sallah Conteh, Jingjing Zhang, Raluca G. Popa, Anthony W. Owen, Cara L. Jonas, Heungjae Choi, Rhian M. Daniel, David Lloyd, Adrian Porch, Christopher H. George
Summary: The ubiquity of wireless electronic-device connectivity has led to microwaves becoming one of the fastest growing forms of electromagnetic exposure. Growing evidence refutes the claim that wireless technologies pose no risk to human health at current safety levels. The potential non-thermal effects of microwave exposure on electrically-excitable tissues, especially the heart, remain controversial.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Gastroenterology & Hepatology
Omry Koren, Liza Konnikova, Petter Brodin, Indira U. Mysorekar, Maria Carmen Collado
Summary: The gut microbiome plays a crucial role in host metabolism and immunity, and its dysbiosis can have detrimental effects on human health. This review focuses on the interactions between the gut microbiome and the immune system during pregnancy and their impact on offspring development. Current knowledge is limited, highlighting the need for further research in this area.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Alessio Lissoni, Paco Hulpiau, Tania Martins-Marques, Nan Wang, Geert Bultynck, Rainer Schulz, Katja Witschas, Henrique Girao, Maarten De Smet, Luc Leybaert
Summary: The research revealed that the activation of ryanodine receptors (RyRs) triggers unitary currents with a single-channel conductance of around 220 pS, which are significantly reduced by knocking down connexin 43 (Cx43). The study also showed that both RyR activation and intracellular Ca2+ elevation are necessary for the opening of Cx43 hemichannels.
CARDIOVASCULAR RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Chen-Chen Jiang, Li-Shan Lin, Sen Long, Xiao-Yan Ke, Kohji Fukunaga, Ying-Mei Lu, Feng Han
Summary: Autism spectrum disorder (ASD) is a common and complex neurodevelopmental disorder with a strong genetic basis. Despite the limited understanding of its etiology, risk factors, and disease progression, significant progress has been made in genetics, identifying hundreds of genes associated with a high risk for autism. The involvement of signal transduction molecular events in pathological processes has important implications for precise molecular targeting in autism. This review provides insights into the mechanisms and clinical implications of signal transduction in autism, as well as future challenges and perspectives.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Plant Sciences
Hisatake Ishida, Uwe John, Shauna A. Murray, Debashish Bhattacharya, Cheong Xin Chan
Summary: Dinoflagellates are diverse eukaryotic microbes found in aquatic environments, with various trophic strategies and the ability to produce bioactive secondary metabolites. They hold great potential for understanding evolutionary and genomic complexities discussed in this article, and the development of fit-to-purpose models that consider their diverse biology and ecology is necessary. The accessibility, tractability, resources, research support, and promise of dinoflagellates as model organisms are also highlighted.
JOURNAL OF PHYCOLOGY
(2023)
Article
Cell Biology
Andras Horvath, Torsten Christ, Jussi T. Koivumaki, Maksymilian Prondzynski, Antonia T. L. Zech, Michael Spohn, Umber Saleem, Ingra Mannhardt, Barbel Ulmer, Evaldas Girdauskas, Christian Meyer, Arne Hansen, Thomas Eschenhagen, Marc D. Lemoine
Article
Cell Biology
Disheet Shah, Chandra Prajapati, Kirsi Penttinen, Reeja Maria Cherian, Jussi T. Koivumaki, Anna Alexanova, Jari Hyttinen, Katriina Aalto-Setala
Review
Cardiac & Cardiovascular Systems
Michelangelo Paci, Kirsi Penttinen, Mari Pekkanen-Mattila, Jussi T. Koivumaki
Summary: The advent of human induced pluripotent stem cell-derived cardiomyocytes has provided a new avenue for studying cardiac arrhythmias, with potential applications in personalized medicine and regenerative medicine. This novel modeling system offers insights into arrhythmogenic triggers and substrates, while also opening doors for future possibilities in the field.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Michelangelo Paci, Jussi T. Koivumaki, Hua Rong Lu, David J. Gallacher, Elisa Passini, Blanca Rodriguez
Summary: This study evaluated the response of three in silico models of hSC-CM to simulated drug action and compared the simulation results with in vitro data for 15 drugs. The results showed qualitative consistency between the observed CTD90 changes in silico and in vitro data, but differences in drug responses across the hSC-CM models were also noted.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Frederik Flenner, Christiane Jungen, Nadine Kuepker, Antonia Ibel, Martin Kruse, Jussi T. Koivumaki, Anna Rinas, Antonia T. L. Zech, Alexandra Rhoden, Paul J. M. Wijnker, Marc D. Lemoine, Anna Steenpass, Evaldas Girdauskas, Thomas Eschenhagen, Christian Meyer, Jolanda van der Velden, Monica Patten-Hamel, Torsten Christ, Lucie Carrier
Summary: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of ventricular arrhythmias and sudden cardiac death, even in the absence of structural changes of the heart. Studies in HCM mouse models suggest that mutations in myofilament components affect Ca2+ homeostasis and may lead to arrhythmia development. This study investigates arrhythmia mechanisms in HCM mice and tests translatability of findings in human samples, highlighting the importance of research in humanlike models.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Physiology
Mohamadamin Forouzandehmehr, Jussi T. Koivumaki, Jari Hyttinen, Michelangelo Paci
Summary: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been increasingly utilized in cardiac research, cardiotoxicity tests, and personalized medicine. A novel electromechanical hiPSC-CM computational model was proposed, showing good agreement with in vitro data under matching conditions. The model has potential for expansion into pharmacological trials and genetic mutation studies in the future.
PHYSIOLOGICAL REPORTS
(2021)
Review
Physiology
Jussi T. Koivumaki, Johan Hoffman, Mary M. Maleckar, Gaute T. Einevoll, Joakim Sundnes
Summary: Mathematical models have greatly advanced cardiovascular physiology research, but barriers between experimental and computational approaches remain, calling for closer integration.
Article
Cell Biology
Djemail Ismaili, Katrin Gurr, Andras Horvath, Lei Yuan, Marc D. Lemoine, Carl Schulz, Jascha Sani, Johannes Petersen, Hermann Reichenspurner, Paulus Kirchhof, Thomas Jespersen, Thomas Eschenhagen, Arne Hansen, Jussi T. Koivumaeki, Torsten Christ
Summary: The physiological importance of NCX in hiPSC-CMs is determined by the strength of the current and the spatial arrangement of proteins involved in Ca2+ extrusion. This study found that hiPSC-CMs have larger NCX currents compared to human ventricular cardiomyocytes. Blocking NCX can shorten action potential duration and increase force in hiPSC-CMs.
Article
Physiology
Mohamadamin Forouzandehmehr, Michelangelo Paci, Jussi T. Koivumaki, Jari Hyttinen
Summary: This study uses a new metabolite-sensitive computational model to analyze the effects of HCM mutations and MAVA, BLEB, and OM on cell mechano-energetics. The results show that MAVA, BLEB, and OM have positive effects on HCM pathophysiology and can restore normal cellular function.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Carl Schulz, Marc D. Lemoine, Giulia Mearini, Jussi Koivumaeki, Jascha Sani, Edzard Schwedhelm, Paulus Kirchhof, Amer Ghalawinji, Monika Stoll, Arne Hansen, Thomas Eschenhagen, Torsten Christ
Summary: This study found that deletion of the PITX2 gene in human induced pluripotent stem cell-derived atrial cardiomyocytes results in some abnormalities similar to electrical remodeling in atrial fibrillation. These findings suggest that the PITX2 gene plays an important role in the occurrence of atrial fibrillation.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2023)
Review
Physiology
Djemail Ismaili, Carl Schulz, Andras Horvath, Jussi T. T. Koivumaki, Delphine Mika, Arne Hansen, Thomas Eschenhagen, Torsten Christ
Summary: Models based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have been proposed in various fields of physiology and pharmacology. The development of hiPSC-CM is expected to enhance the translational power of cardiovascular research, especially in exploring genetic effects on electrophysiological backgrounds similar to humans. However, there are biological and methodological challenges in using hiPSC-CM for experimental electrophysiology. This article discusses some of these challenges that need to be considered when utilizing hiPSC-CM as a physiological model.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Physiology
Hanna Vuorenpaa, Miina Bjoerninen, Hannu Valimaki, Antti Ahola, Mart Kroon, Laura Honkamaki, Jussi T. Koivumaki, Mari Pekkanen-Mattila
Summary: Microphysiological systems (MPS) have gained increasing attention from academia and biomedical industry for their enhanced ability to mimic human physiology. MPS provide an advanced in vitro platform for studying organ and tissue functions in a more accurate manner than traditional single cell cultures or animal models. To achieve this, collaboration from multiple scientific fields is necessary to build MPS with microenvironmental control, high biological complexity, and improved recapitulation of human physiology.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Medicine, Research & Experimental
Chandra Prajapati, Jussi Koivumaki, Mari Pekkanen-Mattila, Katriina Aalto-Setala
Summary: Sex differences exist in the structure and function of the human heart. These differences are observed in electrocardiogram patterns, prevalence and symptom severity of cardiovascular disease. Sex hormones play a significant role in regulating ventricular repolarization.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2022)
Proceedings Paper
Computer Science, Interdisciplinary Applications
Mohamadamin Forouzandehmehr, Chiara Bartolucci, Jari Hyttinen, Jussi T. Koivumaki, Michelangelo Paci
Summary: This study evaluates the effects of acute ischemia on a human adult ventricular cell model and performs a sensitivity analysis. Hyperkalemia significantly affects membrane potential, while acidosis and hypoxia have varying degrees of impact on action potential duration. The study's results are consistent with other simulation data.
2021 COMPUTING IN CARDIOLOGY (CINC)
(2021)
Proceedings Paper
Cardiac & Cardiovascular Systems
Mohamadamin Forouzandehmehr, Nicolo Cogno, Jussi T. Koivumaki, Jari Hyttinen, Michelangelo Paci
2020 COMPUTING IN CARDIOLOGY
(2020)
