Review
Endocrinology & Metabolism
Lina T. Al Kury, Stephanie Chacar, Eman Alefishat, Ali A. Khraibi, Moni Nader
Summary: Diabetes mellitus affects the structure and function of sinoatrial node cells, leading to heart rate variability and cardiomyopathy. The decreased expression of ion transporters and cell-cell communication ports, as well as the abnormal activation of regulatory factors such as RGS4, mitochondrial thioredoxin-2, and CaMKII, contribute to these changes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jari M. Tuomi, Loryn J. Bohne, Tristan W. Dorey, Hailey J. Jansen, Yingjie Liu, Douglas L. Jones, Robert A. Rose
Summary: The study showed that ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function. Ibrutinib increased atrial fibrillation susceptibility and impaired sinus node function, while acalabrutinib had no such effects.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Cardiac & Cardiovascular Systems
Tristan W. Dorey, Megan D. Mcrae, Darrell D. Belke, Robert A. Rose
Summary: This study found that hypertensive heart disease in mice results in impaired heart rate responses to sympathetic nervous system activation. This impairment is caused by up-regulation of PDE4D and reduced effects of cAMP on spontaneous action potential firing in sinoatrial node myocytes.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Peter Hanna, Michael J. Dacey, Jaclyn Brennan, Alison Moss, Shaina Robbins, Sirisha Achanta, Natalia P. Biscola, Mohammed A. Swid, Pradeep S. Rajendran, Shumpei Mori, Joseph E. Hadaya, Elizabeth H. Smith, Stanley G. Peirce, Jin Chen, Leif A. Havton, Zixi (Jack) Cheng, Rajanikanth Vadigepalli, James Schwaber, Robert L. Lux, Igor Efimov, John D. Tompkins, Donald B. Hoover, Jeffrey L. Ardell, Kalyanam Shivkumar
Summary: This study provides an in-depth examination of the innervation of the sinoatrial node by the right atrial ganglionated plexus in porcine and human hearts. It demonstrates the significant phenotypic diversity of neurons in the ganglionated plexus and their role in modulating cardiac function. The findings suggest that intrinsic cardiac neurons play a crucial role in controlling specific regions of the heart and could pave the way for targeted therapies in the future.
CIRCULATION RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Wei Fan, Xuemei Sun, Chao Yang, Juyi Wan, Hongli Luo, Bin Liao
Summary: The pacemaking activity of the heart is primarily determined by spontaneous action potentials (APs) within sinoatrial node (SAN) cells, which rely on membrane clocks and calcium clocks. Nonhomologous arrhythmias result from changes in myocardial function and structure. MicroRNAs (miRNAs) are important regulators of gene expression in cardiomyocytes and play a role in regulating cardiac conduction stability and arrhythmia-induced remodeling. Although the mechanisms of miRNA regulation of ion channels in the heart are not yet clear, these mechanisms may support new therapeutic approaches. This study discusses AP generation and spread in the SAN, as well as the regulation of miRNAs and individual ion channels, with the aim of providing a research basis for miRNA modulation as a new therapeutic target for arrhythmias.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Konstantin Hennis, Martin Biel, Christian Wahl-Schott, Stefanie Fenske
Summary: HCN channels are essential for heart rhythm initiation and regulation, synchronizing pacemaker cells for stable heart function. Entrainment processes in the sinoatrial node play a crucial role in coordinating heart activity and regulating heart rate.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Xi Zheng, Fengjiao Wang, Xiaoxiao Hu, Hua Li, Zhen Guan, Yanding Zhang, Xuefeng Hu
Summary: Specific ablation of Pdgfr alpha in the sinoatrial node (SAN) of mice did not result in any malformation in SAN morphology. Adult mutant mice had normal cardiac function and unaltered Nkx2.5 expression in the SAN, indicating that Pdgfr alpha is dispensable for SAN development after its fate commitment in mice.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biology
Marco Rebecchi, Francesca Fanisio, Fabio Rizzi, Alessandro Politano, Ermenegildo De Ruvo, Cinzia Crescenzi, Germana Panattoni, Marianna Squeglia, Annamaria Martino, Stefano Sasso, Paolo Golia, Giulia Pugliese, Sofia Del Gigante, Domenico Giamundo, Pietro Desimone, Domenico Grieco, Lucia De Luca, Ignazio Giordano, Francesco Barilla, Marco Alfonso Perrone, Leonardo Calo, Ferdinando Iellamo
Summary: Arrhythmogenic substrate, modulating factors, and triggering factors are key players in the pathophysiology of atrial fibrillation (AF). The autonomic nervous system (ANS) not only regulates cardiac rhythm but also has a significant role in the initiation and maintenance of AF. This review provides a detailed description of the autonomic mechanisms involved in AF, focusing on the Autonomic Coumel Triangle hypothesis. It discusses the biomolecular pathways of ANS, the interaction between ANS and cardiomyocytes, and highlights the heterogeneity of the clinical spectrum of ANS and AF.
Review
Biochemistry & Molecular Biology
Anju Singh, Ritushree Kukreti, Luciano Saso, Shrikant Kukreti
Summary: Oxidative stress is a metabolic dysfunction caused by the imbalance between reactive oxygen species production and the body's antioxidant defense system. It is closely related to the development of various noncommunicable diseases. Diabetes mellitus, especially type 2 diabetes, is significantly influenced by oxidative stress, which plays a crucial role in insulin signaling pathways.
Review
Cardiac & Cardiovascular Systems
Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang
Summary: In this review, recent studies on the signaling regulation of sinoatrial node dysfunction (SND) are summarized. Abnormal intercellular and intracellular signaling, heart failure, and diabetes are found to be associated with SND. Understanding the pathogenesis of SND is crucial for the development of effective therapeutic strategies.
CURRENT CARDIOLOGY REPORTS
(2023)
Review
Endocrinology & Metabolism
Alice Duque, Mauro Felippe Felix Mediano, Andrea De Lorenzo, Luiz Fernando Rodrigues Jr
Summary: Cardiovascular autonomic neuropathy (CAN) is a debilitating microvascular complication that primarily affects long-standing type 2 diabetes patients but can also manifest early in the disease progression. The pathophysiology of CAN is complex, involving various risk factors and clinical complications, and early identification and treatment of CAN may help reduce mortality rates for affected individuals.
WORLD JOURNAL OF DIABETES
(2021)
Review
Biochemistry & Molecular Biology
Ioanna Kokkinopoulou, Andriana Diakoumi, Paraskevi Moutsatsou
Summary: Research shows that stress and depression increase the risk of Type 2 Diabetes by impairing the negative feedback of Glucocorticoid in patients, leading to HPA axis hyperactivity and hypercortisolism. Glucocorticoid Receptor has a key role in regulating glucose homeostasis in peripheral tissues, while impaired signaling in Peripheral Blood Mononuclear Cells of T2D patients is linked to metabolic disturbances. Further investigation into selective modulation of GR signaling in T2D therapy is warranted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Ahmad F. Alghanem, Javier Abello, Joshua M. Maurer, Ashutosh Kumar, Chau My Ta, Susheel K. Gunasekar, Urooj Fatima, Chen Kang, Litao Xie, Oluwaseun Adeola, Megan Riker, Macaulay Elliot-Hudson, Rachel A. Minerath, Chad E. Grueter, Robert F. Mullins, Amber N. Stratman, Rajan Sah
Summary: The LRRC8A-dependent volume-regulated anion channel (VRAC) is crucial for regulating vascular function and is particularly important in the context of type 2 diabetes (T2D). LRRC8A modulates endothelial cell function in the vascular system by regulating signaling pathways such as AKT-eNOS.
Review
Pharmacology & Pharmacy
Pietro Mesirca, Vadim V. Fedorov, Thomas J. Hund, Angelo G. Torrente, Isabelle Bidaud, Peter J. Mohler, Matteo E. Mangoni
Summary: Sinoatrial node dysfunction (SND) is a pathological condition caused by the heart's inability to generate a normal sinoatrial node action potential, which may be age-related or genetic. The incidence of SND is expected to increase in the general population, necessitating the need for implanting electronic pacemakers.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Review
Medicine, General & Internal
F. Frost, M. J. Walshaw, D. Nazareth
Summary: Cystic fibrosis (CF) is a common life-threatening inherited condition in the Caucasian population, with pulmonary disease being the main contributor to morbidity. While life expectancy has improved, new challenges have arisen, with an increasing prevalence of CF-related diabetes being a significant issue.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Haaris A. Shiwani, Muhammad Bilal, Muhammad U. Shahzad, Alson Rodrigues, Jehad A. Suliman, Muhammad Soban, Shahzeb Mirza, Nicoleta Lotca, Mohammed R. Ruslan, Danyal Memon, Muhammad A. Arshad, Kiran Fatima, Asma Kamran, Emmanuel E. Egom, Abdul Aziz
Summary: Community-acquired and hospital-acquired COVID-19 exhibit similar mortality rates despite significant differences in baseline characteristics of the patient populations. Distinguishing between community- and hospital-acquired COVID-19 in future studies may provide a more accurate interpretation of results.
RESPIRATORY MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Tristan W. Dorey, Martin Mackasey, Hailey J. Jansen, Megan D. McRae, Loryn J. Bohne, Yingjie Liu, Darrell D. Belke, Logan Atkinson, Robert A. Rose
Summary: NPR-B receptor plays an essential physiological role in maintaining normal heart rate and sinoatrial node function by modulating ion channel function in sinoatrial node myocytes via a cGMP/PDE3/cAMP signaling mechanism.
CARDIOVASCULAR RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
K. Lockhart Jamieson, Robert A. Rose
Article
Geriatrics & Gerontology
Hailey J. Jansen, Motahareh Moghtadaei, Sara A. Rafferty, Robert A. Rose
Summary: This study reveals the association between sinoatrial node (SAN) dysfunction, frailty, and the loss of natriuretic peptide receptor C (NPR-C) in aging. Loss of NPR-C results in accelerated aging and rapid decline in health status, marked by impaired heart rate (HR) and SAN function. Frailty assessment is effective in distinguishing aging-dependent changes in SAN function.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Christian Jons, Andreu Porta-Sanchez, Patrick F. H. Lai, Marianne Wauchop, Stephane Masse, Mohammed Ali Azam, John Asta, Robert A. Rose, Kumaraswamy Nanthakumar
Summary: This study investigated the mechanism and potential means to mitigate the positive chronotropy induced by Liraglutide. It was found that the direct effect of Liraglutide on the sino-atrial node, independent of adrenergic cascade, contributes to the increased heart rate. If blockers are suggested to be more effective than beta-blockers in mitigating LG-induced positive chronotropy.
Article
Cardiac & Cardiovascular Systems
Jari M. Tuomi, Loryn J. Bohne, Tristan W. Dorey, Hailey J. Jansen, Yingjie Liu, Douglas L. Jones, Robert A. Rose
Summary: The study showed that ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function. Ibrutinib increased atrial fibrillation susceptibility and impaired sinus node function, while acalabrutinib had no such effects.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Medicine, General & Internal
P. J. Devereaux, M. Marcucci, T. W. Painter, D. Conen, V Lomivorotov, D. Sessler, M. T. Chan, F. K. Borges, M. J. Martinez-Zapata, C-Y Wang, D. Xavier, S. N. Ofori, M. K. Wang, S. Efremov, G. Landoni, Y. Kleinlugtenbelt, W. Szczeklik, D. Schmartz, A. X. Garg, T. G. Short, M. Wittmann, C. S. Meyhoff, M. Amir, D. Torres, A. Patel, E. Duceppe, K. Ruetzler, J. L. Parlow, V Tandon, E. Fleischmann, C. A. Polanczyk, A. Lamy, S. Astrakov, M. Rao, W. K. K. Wu, K. Bhatt, M. de Nadal, V. V. Likhvantsev, P. Paniagua, H. J. Aguado, R. P. Whitlock, M. H. McGillion, M. Prystajecky, J. Vincent, J. Eikelboom, I Copland, K. Balasubramanian, A. Turan, S. Bangdiwala, D. Stillo, P. L. Gross, T. Cafaro, P. Alfonsi, P. S. Roshanov, E. P. Belley-Cote, J. Spence, T. Richards, T. VanHelder, W. McIntyre, G. Guyatt, S. Yusuf, K. Leslie
Summary: Among patients undergoing noncardiac surgery, tranexamic acid can significantly reduce the occurrence of composite bleeding outcome, but the noninferiority of tranexamic acid for composite cardiovascular outcome was not established.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Robert A. Rose
Review
Cardiac & Cardiovascular Systems
Crystal M. Ripplinger, Alexey V. Glukhov, Matthew W. Kay, Bastiaan J. Boukens, Nipavan Chiamvimonvat, Brian P. Delisle, Larissa Fabritz, Thomas J. Hund, Bjorn C. Knollmann, Na Li, Katherine T. Murray, Steven Poelzing, T. Alexander Quinn, Carol Ann Remme, Stacey L. Rentschler, Robert A. Rose, Nikki G. Posnack
Summary: Cardiac arrhythmias are a significant global health issue, and animal models play a critical role in studying cardiovascular diseases. This article provides an overview of the strengths and limitations of common techniques used to assess cardiac electrophysiology and arrhythmia mechanisms, with a focus on small animal models.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Physiology
Motahareh Moghtadaei, Tristan W. Dorey, Robert A. Rose
Summary: Nonlinear analyses of heart rate variability can quantify the unpredictability, fractal properties, and complexity of heart rate, providing valuable information about cardiovascular health. The Multi-Scale Multi-Fractal Detrended Fluctuation Analysis algorithm is applicable to short time series and robust to noise and nonstationarity, enabling the assessment of HRV at different scales and fractal dynamics. The fractal properties of HRV depend on both the autonomic nervous system activity and intrinsic sinoatrial node function, and evaluating multi-fractality at different time scales is an effective approach for HRV assessment.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Physiology
Hailey. J. J. Jansen, Megan. D. D. McRae, Martin Mackasey, Robert. A. A. Rose
Summary: The study revealed that Ang II mediated atrial electrical and structural remodeling develop earlier and more extensively in the left atrium compared to the right atrium, leading to enhanced AF susceptibility.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Loryn J. Bohne, Hailey J. Jansen, Tristan W. Dorey, Irene M. Daniel, K. Lockhart Jamieson, Darrell D. Belke, Megan D. Mcrae, Robert A. Rose
Summary: This study demonstrates that GLP-1 and its analogues can reduce the incidence of atrial fibrillation and prevent atrial remodeling in patients with type 2 diabetes.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Shubham Banga, Manish Mishra, Stefan D. Heinze-Milne, Hailey J. Jansen, Robert A. Rose, Susan E. Howlett
Summary: Clinical studies suggest a link between low testosterone levels and cardiac arrhythmias in older men. This study found that chronic exposure to low testosterone in aging male mice led to prolonged repolarization, abnormal electrical activity, and increased expression of NaV1.8 sodium channels. Inhibiting the late sodium current or Na(V)1.8 channels could potentially be a new treatment for arrhythmias in older men with testosterone deficiency.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Tristan W. Dorey, Megan D. Mcrae, Darrell D. Belke, Robert A. Rose
Summary: This study found that hypertensive heart disease in mice results in impaired heart rate responses to sympathetic nervous system activation. This impairment is caused by up-regulation of PDE4D and reduced effects of cAMP on spontaneous action potential firing in sinoatrial node myocytes.
CARDIOVASCULAR RESEARCH
(2023)
Review
Genetics & Heredity
Emmanuel Eroume-A Egom, Roger Moyou-Somo, Jean Louis Essame Oyono, Rene Kamgang
Summary: Pulmonary Arterial Hypertension (PAH) is a progressive and devastating disease with increasing genetic and pathophysiological information, but limited success in identifying susceptibility genes and genetic variants due to clinical variability. While BMPR2 and related genes have been extensively studied, advanced gene sequencing technology has led to the discovery of additional gene candidates, potentially providing new opportunities for therapeutic intervention in the future.
APPLICATION OF CLINICAL GENETICS
(2021)
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)