Article
Cardiac & Cardiovascular Systems
Maria Ercu, Michael B. Muecke, Tamara Pallien, Lajos Marko, Anastasiia Sholokh, Carolin Schaechterle, Atakan Aydin, Alexa Kidd, Stephan Walter, Yasmin Esmati, Brandon J. McMurray, Daniella F. Lato, Daniele Yumi Sunaga-Franze, Philip H. Dierks, Barbara Isabel Montesinos Flores, Ryan Walker-Gray, Maolian Gong, Claudia Merticariu, Kerstin Zuehlke, Michael Russwurm, Tiannan Liu, Theda U. P. Batolomaeus, Sabine Pautz, Stefanie Schelenz, Martin Taube, Hanna Napieczynska, Arnd Heuser, Jenny Eichhorst, Martin Lehmann, Duncan C. Miller, Sebastian Diecke, Fatimunnisa Qadri, Elena Popova, Reika Langanki, Matthew A. Movsesian, Friedrich W. Herberg, Sofia K. Forslund, Dominik N. Mueller, Tatiana Borodina, Philipp G. Maass, Sylvia Baehring, Norbert Huebner, Michael Bader, Enno Klussmann
Summary: PDE3A mutations have been found to protect the heart from hypertension-induced cardiac damage by causing adaptive changes and enhancing contractility. These findings could facilitate the development of new treatments to prevent hypertension-induced cardiac damage.
Review
Pharmacology & Pharmacy
Si Chen, Chen Yan
Summary: This review focuses on recent research advances on different PDE isoforms in the heart, discussing their expression patterns and biological functions. Current limitations and future directions in research are also addressed, along with the development of PDE inhibitors.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Review
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
Summary: Myocardial fibrosis, characterized by the expansion of cardiac interstitium through deposition of extracellular matrix proteins, is a common pathophysiologic feature in various myocardial conditions. Activated fibroblasts and myofibroblasts play a central role in cardiac fibrosis, producing matrix proteins and triggering fibrogenic signalling cascades in response to stress. Immune cells, vascular cells, and cardiomyocytes can also contribute to fibrosis, while fibrotic changes may disrupt cardiac function and play a role in arrhythmogenesis.
CARDIOVASCULAR RESEARCH
(2021)
Article
Medicine, Research & Experimental
Rita Hanna, Wared Nour-Eldine, Youakim Saliba, Carole Dagher-Hamalian, Pia Hachem, Pamela Abou-Khalil, Delphine Mika, Audrey Varin, Magali Samia El Hayek, Laetitia Pereira, Nassim Fares, Gregoire Vandecasteele, Aniella Abi-Gerges
Summary: This study found that T1D-induced DCM is associated with cardiac remodeling, steatosis, and fibrosis. Diabetes hearts showed an upregulation of β(1)-AR receptor transcripts at 4 weeks, along with an increase in cAMP levels and improvements in ejection fraction and fraction shortening. However, the expression of β(2)-AR receptors remained unchanged throughout the disease progression.
Article
Medicine, Research & Experimental
Tianbao Ye, Zhiwen Yan, Cheng Chen, Di Wang, Aiting Wang, Taixi Li, Boshen Yang, Xianting Ding, Chengxing Shen
Summary: This study aimed to investigate the cardioprotective role of lactoferrin (Ltf) in myocardial infarction (MI) and its underlying mechanisms. Proteomic analysis revealed that Ltf was significantly upregulated in MI hearts but decreased in circulation, and its expression was positively correlated with cardiac function. Ltf administration attenuated cardiac fibrosis and remodeling, improved cardiac function, and reduced the incidence of heart failure post-MI.
Review
Cell Biology
Jiwen Fan, Meng Ren, Yuquan He
Summary: Cardiac fibrosis is caused by the differentiation of cardiac fibroblasts and excessive accumulation of extracellular matrix, resulting in myocardial stiffness and reduced compliance of the ventricular wall. The conversion of cardiac fibroblasts to myofibroblasts is a crucial step in the pathogenesis of cardiac fibrosis. Recent studies have revealed the significant role of exosomes in diagnosing and treating cardiac fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Michael P. Czubryt, Taben M. Hale
Summary: Cardiac fibrosis is a characteristic of end-stage heart disease, but there are no approved therapies directly targeting the extracellular matrix. Research on cardiac fibroblasts is hindered by the lack of a clear marker.
CELLULAR SIGNALLING
(2021)
Article
Cardiac & Cardiovascular Systems
Maria Raquel Moita, Marta M. Silva, Claudia Diniz, Margarida Serra, Rene M. Hoet, Ana Barbas, Daniel Simao
Summary: This study investigates the role of cardiac fibroblasts in cardiac fibrosis and identifies potential targets for anti-fibrotic therapies. The researchers also demonstrate the suitability of induced pluripotent stem cells as a cell source for preclinical research.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Cardiac & Cardiovascular Systems
Alexandra M. Garvin, Laxmansa C. Katwa
Summary: Primary cardiac fibroblast tissue culture is a necessary tool for studying the signaling mechanisms in heart diseases. Traditional culture methods may induce cell activation and complicate result interpretation. Recent studies focus on the interaction between CF and its environment. This review discusses the factors that impact CF activation in tissue culture.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Cell Biology
Ryan Bonate, Gabriela Kurek, Michael Hrabak, Santanna Patterson, Fernando Padovan-Neto, Anthony R. West, Heinz Steiner
Summary: Dopamine and other neurotransmitters can induce neuroplasticity in the striatum via gene regulation. The expression of phosphodiesterase PDE10A, which controls cyclic nucleotide signaling, is closely related to drug-induced gene regulation and serves as a potential target for modifying drug-induced gene regulation and related neuroplasticity.
Article
Biochemistry & Molecular Biology
Arooma Maryam, Rana Rehan Khalid, Abdul Rauf Siddiqi, Abdulilah Ece
Summary: In this study, a one-drug-multiple-target strategy was used to identify inhibitors with dual specificity through electronic pharmacophore models of PDE5A and PDE3A. The identified lead compounds showed promising inhibitory interactions with conserved catalytic features of the enzymes, suggesting potential for discovery of dual and multipotent drug-like compounds. Further optimization and validation are needed to confirm their therapeutic potential.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Review
Biotechnology & Applied Microbiology
Han Liu, Pengbei Fan, Fanli Jin, Guoyou Huang, Xiaogang Guo, Feng Xu
Summary: This review summarizes the four main biomechanical traits in cardiac fibrosis and categorizes them into static and dynamic types. It provides a comprehensive overview of the impact of different biomechanical traits on cardiac fibrosis, their transduction mechanisms, and in-vitro engineered models targeting these traits, aiding in the identification and prediction of mechano-based therapeutic targets to improve cardiac fibrosis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Cell Biology
Laxmansa C. Katwa, Chelsea Mendoza, Madison Clements
Summary: Cardiovascular disease is the leading cause of death worldwide, and patients with cardiovascular diseases are more susceptible to severe complications of COVID-19. The role of cardiac myofibroblasts in both COVID-19-induced cardiac injury and healing process is crucial.
Article
Cardiac & Cardiovascular Systems
Yafang Zha, Yanyan Li, Zhuowang Ge, Jian Wang, Yuheng Jiao, Jiayan Zhang, Song Zhang
Summary: This study reveals the pro-fibrosis effect of ADAMTS8 in cardiac fibrosis caused by myocardial infarction or pressure overload. ADAMTS8 can damage mitochondrial function, activate the PI3K-Akt pathway and MAPK pathways, and up-regulate YAP expression, leading to increased cardiac fibrosis. This finding suggests that ADAMTS8 may serve as a potential therapeutic target for the treatment of cardiac fibrosis and heart failure.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Quan Liu, Hua-Yang Li, Shun-Jun Wang, Sui-Qing Huang, Yuan Yue, Adilai Maihemuti, Yi Zhang, Lin Huang, Li Luo, Kang-Ni Feng, Zhong-Kai Wu
Summary: The ROCK2-specific inhibitor, belumosudil, effectively alleviates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC through inhibiting cardiac fibroblast activation. The mechanism underlying cardiac fibrosis involves the interaction of ROCK2 with the TGF-β1/Smad2 pathway.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Wei Feng Ma, Chani J. Hodonsky, Adam W. Turner, Doris Wong, Yipei Song, Jose Verdezoto Mosquera, Alexandra Ligay, Lotte Slenders, Christina Gancayco, Huize Pan, Nelson B. Barrientos, David Mai, Gabriel F. Alencar, Katherine Owsiany, Gary K. Owens, Muredach P. Reilly, Mingyao Li, Gerard Pasterkamp, Michal Mokry, Sander W. van der Laan, Bohdan B. Khomtchouk, Clint L. Miller
Summary: This study developed a workflow for single-cell RNA sequencing (scRNA-seq) analysis in atherosclerosis research and applied it to investigate a previously published human coronary single-cell dataset. The study revealed different derivations of fibroblast-like cells from smooth muscle cells in the atherosclerotic environment, and identified key changes in gene expression along their de-differentiation path. Additionally, the study highlighted potential mechanisms for several drugs in the atherosclerotic cellular environment. The development of the interactive web application PlaqView also allows non-expert scientists to explore and analyze relevant datasets.
Article
Cardiac & Cardiovascular Systems
Ying Wang, Hua Gao, Fudi Wang, Zhongde Ye, Michal Mokry, Adam W. Turner, Jianqin Ye, Simon Koplev, Lingfeng Luo, Tom Alsaigh, Shaunak S. Adkar, Maria Elishaev, Xiangyu Gao, Lars Maegdefessel, Johan L. M. Bjorkegren, Gerard Pasterkamp, Clint L. Miller, Elsie G. Ross, Nicholas J. Leeper
Summary: This study reveals that vascular smooth muscle cells (SMCs) undergo dedifferentiation and activation of pro-inflammatory pathways during the development of atherosclerosis. ATF3, a transcription factor, is identified as an upstream regulator of this transition. ATF3 represses the transition of SMCs towards a subset of cells that promote vascular inflammation by activating the complement cascade. The expression of ATF3 is negatively correlated with complement component C3, and genetic variations that reduce ATF3 expression are associated with an increased risk for atherosclerosis.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Redouane Aherrahrou, Dillon Lue, R. Noah Perry, Yonathan Tamrat Aberra, Mohammad Daud Khan, Joon Yuhl Soh, Tiit Ord, Prosanta Singha, Qianyi Yang, Huda Gilani, Ernest Diez Benavente, Doris Wong, Jameson Hinkle, Lijiang Ma, Gloria M. Sheynkman, Hester M. den Ruijter, Clint L. Miller, Johan L. M. Bjoerkegren, Minna U. Kaikkonen, Mete Civelek
Summary: Coronary artery disease (CAD) is the leading cause of death globally. This study identified over 175 loci associated with CAD and found that they regulate gene expression in vascular smooth muscle cells (SMCs). The results also showed unique gene expression patterns in SMCs and sex-specific gene regulation. These findings provide insights into the molecular mechanisms underlying genetic susceptibility to CAD.
CIRCULATION RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Sina Safabakhsh, Wei Feng Ma, Clint L. L. Miller, Zachary Laksman
Summary: Single-cell RNA sequencing has the potential to improve diagnostics and treatment of cardiovascular diseases, with current focus on structural or atherosclerotic heart diseases and potential future applications in cardiac electrophysiology and cardio-oncology.
CURRENT OPINION IN CARDIOLOGY
(2023)
Article
Medicine, Research & Experimental
Atsushi Sakamoto, Rika Kawakami, Masayuki Mori, Liang Guo, Ka Hyun Paek, Jose Verdezoto Mosquera, Anne Cornelissen, Saikat Kumar B. Ghosh, Kenji Kawai, Takao Konishi, Raquel Fernandez, Daniela T. Fuller, Weili Xu, Aimee E. Vozenilek, Yu Sato, Hiroyuki Jinnouchi, Sho Torii, Adam W. Turner, Hirokuni Akahori, Salome Kuntz, Craig C. Weinkauf, Parker J. Lee, Robert Kutys, Kathryn Harris, Alfred Lawrence Killey, Christina M. Mayhew, Matthew Ellis, Leah M. Weinstein, Neel V. Gadhoke, Roma Dhingra, Jeremy Ullman, Armella Dikongue, Maria E. Romero, Frank D. Kolodgie, Clint I. Miller, Renu Virmani, Aloke V. Finn
Summary: Vascular calcification (VC) and atherosclerosis coexist, but it is unclear why rupture-prone high-risk plaques do not typically calcify extensively. In this study, the researchers found that CD163+ macrophages, which are involved in atherosclerosis, have an inverse correlation with VC in human arteries. They also discovered that these macrophages inhibit VC through NF-KB-induced hyaluronan synthase (HAS), an enzyme that plays a role in the formation of the extracellular matrix. These findings provide insights into the mechanism by which CD163+ macrophages promote high-risk plaque development by inhibiting VC.
Review
Biochemistry & Molecular Biology
Milda Folkmanaite, Manuela Zaccolo
Summary: Cyclic adenosine monophosphate (cAMP) is a crucial intracellular messenger involved in cardiac function regulation. It forms nanodomains to match extracellular stimuli with appropriate cellular responses. Dysregulation of cAMP compartmentalization is associated with cardiovascular diseases.
BIOSCIENCE REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Wei Zhang, Jinjing Zhao, Lin Deng, Nestor Ishimwe, Jessica Pauli, Wen Wu, Shengshuai Shan, Wolfgang Kempf, Margaret D. Ballantyne, David Kim, Qing Lyu, Matthew Bennett, Julie Rodor, Adam W. Turner, Yao Wei Lu, Ping Gao, Mihyun Choi, Ganesh Warthi, Ha Won Kim, Margarida M. Barroso, William B. Bryant, Clint L. Miller, Neal L. Weintraub, Lars Maegdefessel, Joseph M. Miano, Andrew H. Baker, Xiaochun Long
Summary: The study discovered that INKILN is involved in the regulation of vascular smooth muscle cell (VSMC) inflammation and plays a role in the development of atherosclerosis and abdominal aortic aneurysm. INKILN activates the expression of inflammatory genes through interaction with MKL1 in VSMCs. This study provides a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions.
Article
Cardiac & Cardiovascular Systems
Doris Wong, Gaelle Auguste, Christian L. Lino Cardenas, Adam W. Turner, Yixuan Chen, Yipei Song, Lijiang Ma, R. Noah Perry, Redouane Aherrahrou, Maniselvan Kuppusamy, Chaojie Yang, Jose Verdezoto Mosquera, Collin J. Dube, Mohammad Daud Khan, Meredith Palmore, Jaspreet Kalra, Maryam Kavousi, Patricia A. Peyser, Ljubica Matic, Ulf Hedin, Ani Manichaikul, Swapnil K. Sonkusare, Mete Civelek, Jason C. Kovacic, Johan L. M. Bjorkegren, Rajeev Malhotra, Clint L. Miller
Summary: Genome-wide association studies have identified numerous loci associated with vascular diseases, but their mechanistic insights are lacking. This study implicates UFL1-FHL5 as a candidate causal gene for coronary artery disease/myocardial infarction and reveals its role in regulating smooth muscle cell contraction. Further analysis shows that FHL5 mediates vascular disease risk through transcriptional regulation of downstream vascular remodeling genes.
CIRCULATION RESEARCH
(2023)
Review
Biology
Jakub Tomek, Manuela Zaccolo
Summary: In the past 30 years, the understanding of cyclic adenosine 3',5'-monophosphate (cAMP) signaling has changed from a linear pathway to a complex network, where spatial regulation of cAMP plays a critical role. This new model provides novel insights into cardiac myocyte physiology and provides a framework for identifying disease mechanisms, particularly in the regulation of cardiac rhythm.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yipei Song, Francesco Cisternino, Joost M. M. Mekke, Gert J. J. de Borst, Dominique P. V. de Kleijn, Gerard Pasterkamp, Aryan Vink, Craig A. A. Glastonbury, Sander W. W. van der Laan, Clint L. L. Miller
Summary: In this study, a unique approach called 'EntropyMasker' based on image entropy was developed for the task of foreground and background segmentation in histology whole-slide images. The method was evaluated on 97 high-resolution images and showed the highest sensitivity and Jaccard similarity index compared to four widely used segmentation methods.
SCIENTIFIC REPORTS
(2023)
Article
Rheumatology
Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till F. M. Andlauer, Michelle S. Yau, April E. Hartley, Ben Michael Brumpton, Humaira Rasheed, John P. Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M. Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A. Peyser, Maryam Kavousi, Paul S. de Vries, Clint L. Miller, Maxime Bos, Sander W. van Der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V. Holmes, George Davey Smith, Jonathan H. Tobias
Summary: This study suggests that lowering sclerostin may increase the risk of hypertension, type 2 diabetes mellitus, myocardial infarction, and the extent of coronary artery calcification. Therefore, strategies should be implemented to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its risk factors.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Mengxue Zhang, Jing Li, Qingwei Wang, Go Urabe, Runze Tang, Yitao Huang, Jose Verdezoto Mosquera, K. Craig Kent, Bowen Wang, Clint L. Miller, Lian-Wang Guo
Summary: This study uncovers a previously unknown role for EED in Ccnd1 activation, likely via its cooperativity with BRD4 that enhances each other's reader function; i.e., activating pro-proliferative Ccnd1 while repressing anti-proliferative P57.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Cell Biology
Alice Varley, Andreas Koschinski, Mark R. Johnson, Manuela Zaccolo
Summary: Preterm birth is a major cause of childhood mortality and morbidity. Understanding the role of cAMP signaling in controlling myometrial contractility is crucial for reducing the adverse outcomes associated with dysfunctional labor. This study used genetically encoded cAMP reporters to investigate cAMP signaling in human myometrial smooth muscle cells. The findings showed significant differences in the dynamics of cAMP response in different cellular compartments, and also highlighted the importance of cell model choice and culture conditions when studying cAMP signaling in myometrial cells.
Review
Biochemistry & Molecular Biology
Duangnapa Kovanich, Teck Yew Low, Manuela Zaccolo
Summary: cAMP is a second messenger that plays a crucial role in regulating cellular functions. The compartmentalization of cAMP signaling is essential for its specificity, and the formation of dynamic signaling domains is responsible for precise spatiotemporal regulation. Proteomics can be used to identify the components of these domains and define the dynamic landscape of cellular cAMP signaling. Understanding compartmentalized cAMP signaling in physiological and pathological conditions can provide insights into disease mechanisms and guide the development of precision medicine interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Sport Sciences
Scott D. Tagliaferri, Daniel L. Belavy, Steven J. Bowe, Matthew J. Clarkson, David Connell, Emma A. Craige, Romina Gollan, Luana C. Main, Clint T. Miller, Ulrike H. Mitchell, Niamh L. Mundell, Christopher Neason, Claire L. Samanna, David Scott, Jamie L. Tait, Grace E. Vincent, Patrick J. Owen
Summary: This study aims to evaluate the effectiveness of a progressive interval running programme on intervertebral disc (IVD) health and clinical outcomes in adults with chronic low back pain. The findings of this study have the potential to reduce the burden of disease and improve IVD health in a susceptible population.
BMJ OPEN SPORT & EXERCISE MEDICINE
(2023)