Article
Biology
Rene Solano Fonseca, Patrick Metang, Nathan Egge, Yingjian Liu, Kielen R. Zuurbier, Karthigayini Sivaprakasam, Shawn Shirazi, Ashleigh Chuah, Sonja L. B. Arneaud, Genevieve Konopka, Dong Qian, Peter M. Douglas
Summary: Concussion, a type of traumatic brain injury, can increase the risk of developing Alzheimer's and Parkinson's disease. Studies suggest that different types of brain cells, including neurons and astrocytes, may be damaged during a concussion, with astrocytes potentially playing a protective role in preserving dopaminergic neurons. The balance of energy production and metabolism in brain cells, particularly in response to trauma, may be crucial in preventing cell death and neurodegeneration.
Article
Pharmacology & Pharmacy
Liqiang Sun, Wenlong Zhang
Summary: The study demonstrates that preconditioning MSCs with ghrelin can enhance cardioprotective effects, especially in elderly subjects, following IR injury. Preconditioned MSCs increase autophagy flux by downregulating Beclin-1 and P62 protein overexpression, and increasing LC3-II expression and the LC3-II/LC3-I ratio. Moreover, combining NMN with ghrelin-preconditioned MSCs synergistically enhances protective effects on infarct size and mitochondrial function.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Cora N. Betsinger, Connor S. R. Jankowski, William A. Hofstadter, Joel D. Federspiel, Clayton J. Otter, Pierre M. Jean Beltran, Ileana M. Cristea
Summary: The study reveals how the prevalent pathogen HCMV increases mitochondrial metabolism and cellular respiration through the viral protein pUL13, promoting virus replication. Interaction of pUL13 with the MICOS complex alters mitochondrial structure and affects oxidative phosphorylation process in cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Alex Gallinat, Gemma Vilahur, Teresa Padro, Lina Badimon
Summary: Infarct size is a major risk predictor for heart failure after acute myocardial infarction (AMI). The discovery of conditioning phenomena has revealed the existence of endogenous protective mechanisms that can limit infarct size after revascularization. However, most strategies aiming to reduce infarct size have failed in clinical studies, highlighting the need for cardioprotection. This study used a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium in a swine model of AMI. The results identified cardiac metabolism as a driver of cardioprotection and highlighted the role of post-conditioning in promoting metabolic reprogramming of the myocardium and a protective response mediated by VDAC2 and DJ-1 in the mitochondria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Michael Harris, Junhui Sun, Karen Keeran, Angel Aponte, Komudi Singh, Danielle Springer, Marjan Gucek, Mehdi Pirooznia, Matthew E. Cockman, Elizabeth Murphy, Leslie M. Kennedy
Summary: This study demonstrates that deletion of Ogfod1 alters the myocardial proteome and metabolome, providing protection against ischemia-reperfusion injury.
CARDIOVASCULAR RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Ning Sheng, Zhihui Zhang, Hao Zheng, Congyu Ma, Menglin Li, Zhe Wang, Lulu Wang, Jiandong Jiang, Jinlan Zhang
Summary: This study discovered a molecule called scutellarin (SG) that can treat neurodegenerative diseases by regulating energy metabolism and repairing mitochondrial damage. The molecule was found to protect mitochondria through the PDK-PDC axis and mitochondrial glucose oxidation.
Article
Biochemistry & Molecular Biology
Malgorzata Beresewicz-Haller, Olga Krupska, Pawel Bochomulski, Danuta Dudzik, Anita Checinska, Wojciech Hilgier, Coral Barbas, Krzysztof Zablocki, Barbara Zablocka
Summary: The study found that mitochondrial GLS1 activity against ischemic episodes is regulated by PKC beta II. Through the modulation of GLS1 activity and remodeling of mitochondria after exposure to ischemia-reperfusion, the hippocampal CA2-4 and DG regions show strong resistance, while the susceptible CA1 region does not experience the same changes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Viktoria Pevna, Georges Wagnieres, Daniel Jancura, Veronika Huntosova
Summary: Photobiomodulation (PBM) therapy enhances photodynamic therapy (PDT) efficacy by changing the distribution and concentration of protein kinase Cd (PKCd) in cancer cells and inducing phosphorylation in specific organelles. Despite the neutralization by autophagy, PDT can effectively exploit this process to generate apoptosis in cancer treatment, improving treatment efficacy and opening up new prospects.
Article
Cardiac & Cardiovascular Systems
Sean Brennan, Simona Esposito, Muhammad I. M. Abdelaziz, Christopher A. A. Martin, Samir Makwana, Mark W. W. Sims, Iain B. B. Squire, Parveen Sharma, Amy E. E. Chadwick, Richard D. Rainbow
Summary: Hyperglycemia at the time of myocardial infarction has a negative impact on prognosis, regardless of prior diabetes diagnosis. Glucose is suggested to be the damaging factor. In ex vivo models, it was demonstrated that acutely elevated glucose has harmful effects that are PKC alpha/beta-dependent. Cardioprotection can be obtained by inhibiting PKC alpha/beta. Short pretreatments with high glucose revealed time-dependent glucose cardiotoxicity, and inhibition of PKC alpha/beta was studied as a potential mechanism to reverse the toxicity. In isolated non-diabetic rat cardiomyocytes, exposure to elevated glucose for more than 7.5 minutes led to cardiotoxicity, while exposure to metabolic inhibition following 5-minute high glucose showed time-dependent protection lasting around 15 minutes. This protection was further enhanced with PKC alpha/beta inhibition. Cardioprotection was measured by delayed contractile failure, K-ATP channel activation, improved contractile and Ca2+ transient recovery, and increased cell survival. Pre-ischemic treatment with high glucose in a whole-heart coronary ligation protocol also revealed the presence of protection with PKC alpha/beta inhibition. Selective PKC alpha/beta inhibition enhances cardioprotection, suggesting that glycaemic control with PKC inhibition may be a potential therapeutic strategy for myocardial infarction and elective cardiac surgery.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Physiology
Yuhu Lv, Lin Cheng, Fenglin Peng
Summary: Mitochondria-associated endoplasmic reticulum membranes (MAMs) play important roles in intracellular signaling and the regulation of intracellular Ca2+/lipid homeostasis, mitochondrial dynamics, autophagy/mitophagy, apoptosis, and inflammation. Exercise or EP may exert cardioprotective effects by modulating proteins on MAMs and subsequently affecting MAMs.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Christian Morsczeck, Michela De Pellegrin, Anja Reck, Torsten E. Reichert
Summary: Research on osteogenic differentiation in dental follicle cells (DFCs) has shown that the BMP2/DLX3 signaling pathway only supports the early phase of differentiation, inhibition of PKCs promotes DFCs mineralization, and osteogenic differentiation is sensitive to changes in signaling pathways such as AKT and PKC. Metabolic processes also play a crucial role in the osteogenic differentiation of DFCs.
Article
Clinical Neurology
Xiaopeng Chen, Yiyun Liu, Juncai Pu, Siwen Gui, Dongfang Wang, Xiaogang Zhong, Weiyi Chen, Wei Tao, Yue Chen, Xiang Chen, Peng Xie
Summary: This study identified differential expression of proteins in the intestines of macaques with depression-like behaviors. The downregulation of multiple proteins and alterations in metabolism and gut microbiota were observed. Key proteins involved in mitochondrial function and energy metabolism were inhibited, potentially leading to disruptions in energy metabolism.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Matus Valach, Jose Angel Gonzalez Alcazar, Matt Sarrasin, B. Franz Lang, Michael W. Gray, Gertraud Burger
Summary: The mitochondria of jakobids have mt-rRNA structures similar to bacteria, but their mitochondrial ribosomal protein composition is complex, comparable to that of animals or fungi. The high conservation of jakobid sequences helps clarify the identity of certain mtRPs as divergent homologs of conserved M-mtRPs. This suggests that the acquisition of numerous M-mtRPs in the last eukaryotic common ancestor allowed mt-rRNAs to evolve along a broad range of trajectories across lineages.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Cell Biology
Tara R. Richman, Judith A. Ermer, Stefan J. Siira, Irina Kuznetsova, Christopher A. Brosnan, Giulia Rossetti, Jessica Baker, Kara L. Perks, Henrietta Cserne Szappanos, Helena M. Viola, Nicola Gray, Mark Larance, Livia C. Hool, Steven Zuryn, Oliver Rackham, Aleksandra Filipovska
Summary: This study demonstrates that changes in mitochondrial protein synthesis rate and fidelity have tissue-specific outcomes under environmental stress like a high-fat diet. Mutant mice with error-prone or hyper-accurate mitochondrial ribosomes showed divergent effects in heart and liver, reflecting complex transcriptional and signaling responses.
Article
Cardiac & Cardiovascular Systems
Luigi Ferrucci, Julian Candia, Ceereena Ubaida-Mohien, Alexey Lyashkov, Nirad Banskota, Christiaan Leeuwenburgh, Stephanie Wohlgemuth, Jack M. Guralnik, Mary Kaileh, Dongxue Zhang, Robert Sufit, Supriyo De, Myriam Gorospe, Rachel Munk, Charlotte A. Peterson, Mary M. McDermott
Summary: Transcriptomic and proteomic analyses revealed activation of hypoxia-compensatory mechanisms, inflammation, fibrosis, apoptosis, angiogenesis, unfolded protein response, and nerve and muscle repair in peripheral artery disease (PAD) muscle. Aberrant proportions of mitochondrial respiratory proteins and reduced activity of rate-limiting glycolytic enzymes were also observed. These mechanisms may serve as potential targets for disease modification.
CIRCULATION RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Sean M. Davidson, Chantal M. Boulanger, Elena Aikawa, Lina Badimon, Lucio Barile, Christoph J. Binder, Alain Brisson, Edit Buzas, Costanza Emanueli, Felix Jansen, Miroslava Katsur, Romaric Lacroix, Sai Kiang Lim, Nigel Mackman, Manuel Mayr, Philippe Menasche, Rienk Nieuwland, Susmita Sahoo, Kaloyan Takov, Thomas Thum, Pieter Vader, Marca H. M. Wauben, Kenneth Witwer, Joost P. G. Sluijter
Summary: This article provides an overview of the techniques and technologies available for the separation and characterization of EVs from different sources. It discusses methods for determining the protein, RNA, and lipid content of EVs. The guidance provided in this document is important for investigating the role of EVs in cardiovascular diseases and highlights key methodological issues to consider.
CARDIOVASCULAR RESEARCH
(2023)
Editorial Material
Endocrinology & Metabolism
Nicole Bechmann, Andreas Barthel, Andreas Schedl, Stephan Herzig, Zsuzsanna Varga, Catherine Gebhard, Manuel Mayr, Constanze Hantel, Felix Beuschlein, Christian Wolfrum, Nikolaos Perakakis, Lucilla Poston, Cynthia L. Andoniadou, Richard Siow, Raul R. Gainetdinov, Arad Dotan, Yehuda Shoenfeld, Geltrude Mingrone, Stefan R. Bornstein
Summary: Current evidence shows that COVID-19 severity and mortality are higher in men compared to women, while women may be at a higher risk of reinfection and long-term COVID-19 development. Differences between sexes have also been observed in other infectious diseases and vaccine responses. This could be explained by sex-specific expression patterns of proteins involved in virus binding and entry, as well as divergent reactions of the immune and endocrine systems to acute stress. Understanding the role of sex hormones, comorbidities, and sex chromosome complement in COVID-19 could have implications for disease treatment, public health measures, and follow-up of patients predisposed to long COVID. Considering sex differences in future pandemic surveillance and COVID-19 patient treatment may lead to better disease stratification and improved outcomes.
LANCET DIABETES & ENDOCRINOLOGY
(2022)
Review
Oncology
Paul Benjamin Loughrey, Federico Roncaroli, Estelle Healy, Philip Weir, Madhu Basetti, Ruth T. Casey, Steven J. Hunter, Marta Korbonits
Summary: Pituitary neuroendocrine tumours (PitNETs) associated with paragangliomas or phaeochromocytomas are rare, but are linked to SDHx and MAX variants. Prolactinomas are the most common type of PitNETs, followed by somatotrophinomas, clinically non-functioning tumours, and corticotrophinomas in SDHx variant patients.
ENDOCRINE-RELATED CANCER
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Carlos G. Santos-Gallego, Manuel Mayr, Juan Badimon
Article
Hematology
Paul C. Armstrong, Harriet E. Allan, Nicholas S. Kirkby, Clemens Gutmann, Abhishek Joshi, Marilena Crescente, Jane A. Mitchell, Manuel Mayr, Timothy D. Warner
Summary: This study developed a method to label platelet age and found that young platelets exhibit different functional and molecular characteristics compared to older platelets, with increased responsiveness and contribution to thrombus formation. The decrease in thrombotic function with age is accompanied by changes in surface protein expression.
Article
Cell Biology
Meredith Whitehead, Syabira Yusoff, Sadia Ahmad, Lukas Schmidt, Manuel Mayr, Jillian Madine, David Middleton, Catherine M. Shanahan
Summary: Vascular amyloidosis, caused by the aggregation of peptide monomers into insoluble amyloid, is a common age-related pathology. This study found that extracellular vesicles (EVs) and HSPG2 in the extracellular matrix (ECM) play key roles in medin accumulation, contributing to the development of age-associated aortic medial amyloid (AMA).
Editorial Material
Cardiac & Cardiovascular Systems
Clemens Gutmann, Thomas A. Zelniker, Manuel Mayr
EUROPEAN HEART JOURNAL
(2022)
Review
Biochemical Research Methods
Rasheed Sule, Gabriela Rivera, Aldrin Gomes
Summary: Western blotting is a powerful technique for detecting or semiquantifying individual proteins from complex mixtures of cell or tissue extracts. This article provides a comprehensive overview of the history, theory, protocol, and applications of western blotting. It also discusses lesser known but significant problems in the field and troubleshooting techniques. This work serves as a primer and guide for new western blotting researchers and those seeking a better understanding of the technique or improved results.
Editorial Material
Cardiac & Cardiovascular Systems
Lukas E. Schmidt, Walter S. Speidl, Sotirios Tsimikas, Manuel Mayr
EUROPEAN HEART JOURNAL
(2023)
Review
Cardiac & Cardiovascular Systems
Nick S. Nurmohamed, Jordan M. Kraaijenhof, Manuel Mayr, Stephen J. Nicholls, Wolfgang Koenig, Alberico L. Catapano, Erik S. G. Stroes
Summary: Given the limited accuracy of clinically used risk scores, novel risk algorithms based on proteomics and lipidomics data could provide more reliable ASCVD risk prediction. Retrospective studies have consistently shown the additive prognostic value of these panels over traditional risk scores, and prospective studies are needed to determine their clinical utility.
EUROPEAN HEART JOURNAL
(2023)
Article
Cell Biology
Hoyee Tsui, Sebastiaan Johannes van Kampen, Su Ji Han, Viviana Meraviglia, Willem B. van Ham, Simona Casini, Petra van der Kraak, Aryan Vink, Xiaoke Yin, Manuel Mayr, Alexandre Bossu, Gerard A. Marchal, Jantine Monshouwer-Kloots, Joep Eding, Danielle Versteeg, Hesther de Ruiter, Karel Bezstarosti, Judith Groeneweg, Sjoerd J. Klaasen, Linda W. Van Laake, Jeroen A. A. Demmers, Geert J. P. L. Kops, Christine L. Mummery, Toon A. B. Van Veen, Carol Ann Remme, Milena Bellin, Eva van Rooij
Summary: Arrhythmogenic cardiomyopathy (ACM) is a progressive cardiac disease caused by inherited mutations, such as plakophilin-2 (PKP2), which lead to decreased expression of desmosomal and adherens junction (AJ) proteins. In vitro and in vivo experiments demonstrated impaired contractility, cardiac dysfunction, and fibrosis associated with PKP2 mutations. Proteomics analysis revealed the involvement of the ubiquitin-proteasome system (UPS) in ACM pathogenesis, and inhibition of UPS improved cardiomyocyte function. The study highlights the potential therapeutic strategy of targeting protein degradation and improving desmosomal protein stability for ACM treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Konstantinos Theofilatos, Stefan Stojkovic, Maria Hasman, Sander W. van der Laan, Ferheen Baig, Javier Barallobre-Barreiro, Lukas Emanuel Schmidt, Siqi Yin, Xiaoke Yin, Sean Burnap, Bhawana Singh, Jude Popham, Olesya Harkot, Stephanie Kampf, Maja Carina Nackenhorst, Andreas Strassl, Christian Loewe, Svitlana Demyanets, Christoph Neumayer, Martin Bilban, Christian Hengstenberg, Kurt Huber, Gerard Pasterkamp, Johann Wojta, Manuel Mayr
Summary: Using proteomics, this study identified molecular types of atherosclerotic lesions and their associations with histology, imaging, and cardiovascular outcomes. Proteomic signatures of plaque inflammation and calcification were identified and validated. Sex differences in atherosclerosis were also revealed. Protein signatures were used to predict future cardiovascular mortality, outperforming imaging and histology.
CIRCULATION RESEARCH
(2023)
Article
Hematology
Yasushi Ueki, Jonas D. Haner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bar, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R. Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C. M. Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C. Koskinas, Manuel Mayr, Lorenz Raber
Summary: Alirocumab has no significant effect on platelet reactivity and platelet-derived noncoding RNAs in AMI patients receiving dual antiplatelet therapy with a potent P2Y12 inhibitor.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Multidisciplinary Sciences
Sara G. Romeo, Ilaria Secco, Edoardo Schneider, Christina M. Reumiller, Celio X. C. Santos, Anna Zoccarato, Vishal Musale, Aman Pooni, Xiaoke Yin, Konstantinos Theofilatos, Silvia Cellone Trevelin, Lingfang Zeng, Giovanni E. Mann, Varun Pathak, Kevin Harkin, Alan W. Stitt, Reinhold J. Medina, Andriana Margariti, Manuel Mayr, Ajay M. Shah, Mauro Giacca, Anna Zampetaki
Summary: The microvasculature is critical for the delivery of oxygen and metabolites throughout tissues. In this study, human blood vessel organoids (BVOs) were used to show that CTGF is a critical paracrine regulator of microvascular integrity that can restore pericyte coverage and vessel structure.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mirjana Malnar Crnigoj, Ursa Cercek, Xiaoke Yin, Manh Tin Ho, Barbka Repic Lampret, Manuela Neumann, Andreas Hermann, Guy Rouleau, Beat Suter, Manuel Mayr, Boris Rogelj
Summary: In this study, the authors found that the expansion of GGGGCC repeat in the C9orf72 gene leads to amyotrophic lateral sclerosis and frontotemporal dementia. They identified CCCCGG antisense repeat RNA as the main binder and inhibitor of phenylalanine-tRNA synthetase, resulting in decreased levels of tRNAphe and phenylalanine-rich proteins.
NATURE COMMUNICATIONS
(2023)
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)