Review
Cell Biology
Anika Cappenberg, Marina Kardell, Alexander Zarbock
Summary: Selectins play important roles in the initial contact and rolling of neutrophils along the endothelium, and the recruitment of neutrophils and activation of integrins are closely related to selectin-mediated signaling pathways.
Article
Mechanics
Wei Kang, Long Li, Jizeng Wang
Summary: During inflammation, the rolling adhesion of leukocytes in blood vessels mediated by selectin and integrin molecules is influenced by shear flow. Experimental and simulation results reveal that the dynamic competition between selectins and integrins, as well as the elongation of selectin bonds, play important roles in regulating the rolling speed and adhesion level of leukocytes.
JOURNAL OF APPLIED MECHANICS-TRANSACTIONS OF THE ASME
(2022)
Article
Biochemistry & Molecular Biology
Andrea Galassi, Paola Ciceri, Valeria Bono, Lorenza Magagnoli, Matteo Sala, Luisa Artioli, Roberta Rovito, Mohamad Hadla, Vaibhav Yellenki, Antonella D'Arminio Monforte, Camilla Tincati, Mario Cozzolino, Giulia Marchetti
Summary: A cytokine storm plays a crucial role in the pathogenesis of severe COVID-19 infection, and certain biomarkers have been linked to mortality. Chronic kidney disease (CKD) is identified as a risk factor for severe COVID-19. This study investigated the association between specific biomarkers and mortality in COVID-19 patients, and examined the differences in patients with estimated glomerular filtration rate (eGFR) higher or lower than 45 mL/min. The results showed that patients with lower eGFR had higher levels of GDF-15, CD-25, and RAGE, and these biomarkers were significantly elevated in non-survivors and patients requiring ventilation. GDF-15 quartiles were independently associated with mortality risk, with higher quartiles indicating a higher risk. The association between GDF-15 quartiles and mortality risk was stronger in patients with lower eGFR. These findings suggest the potential of exploring the inhibitory effect of the GDF-15 signaling pathway in CKD.
Article
Cardiac & Cardiovascular Systems
Eri Toda Kato, David A. Morrow, Jianping Guo, David D. Berg, Michael A. Blazing, Erin A. Bohula, Marc P. Bonaca, Christopher P. Cannon, James A. de Lemos, Robert P. Giugliano, Petr Jarolim, Tibor Kempf, L. Kristin Newby, Michelle L. O'Donoghue, Marc A. Pfeffer, Nader Rifai, Stephen D. Wiviott, Kai C. Wollert, Eugene Braunwald, Marc S. Sabatine
Summary: Levels of growth differentiation factor 15 (GDF-15) have been associated with various cardiovascular events. This study analyzed data from eight trials and found that higher GDF-15 concentration was independently associated with increased rates of cardiovascular death/hospitalization for heart failure and major adverse cardiovascular events. However, the prognostic association of GDF-15 with future myocardial infarction and stroke remained significant only in patients stabilized after recent acute coronary syndrome or with stable atherosclerotic cardiovascular disease, not in acute coronary syndrome patients.
EUROPEAN HEART JOURNAL
(2023)
Article
Critical Care Medicine
Shinya Onishi, Takeshi Ebihara, Yuki Togami, Tsunehiro Matsubara, Hisatake Matsumoto, Akinori Osuka, Hiroshi Ogura, Jun Oda
Summary: The study found that in the acute phase of severe burns, GDF-15 levels were associated with mortality and SOFA scores, making it a potential marker for assessing severity and prognosis.
Review
Biochemistry & Molecular Biology
Adrian C. Eddy, Aaron J. Trask
Summary: GDF-15 is often elevated in cardiovascular disease and diabetes, making it a potential biomarker for these conditions, while also playing a protective role. This review focuses on the potential functions of GDF-15 in regulating metabolism, insulin sensitivity, and the cardiovascular system through signaling pathways.
CYTOKINE & GROWTH FACTOR REVIEWS
(2021)
Article
Medicine, General & Internal
Leticia Alserawan, Patricia Penacoba, Sandra Elizabet Orozco Echevarria, Diego Castillo, Esther Ortiz, Laura Martinez-Martinez, Esther Moga Naranjo, Pere Domingo, Ivan Castellvi, Candido Juarez, Anais Mariscal
Summary: GDF-15 is upregulated in inflammatory and oxidative stress conditions, and its levels are higher in severe COVID-19 patients, correlating with markers of inflammation and poor respiratory function. GDF-15 shows potential as a biomarker for stratifying COVID-19 cases based on severity.
Review
Cell Biology
Zahra Hasanpour Segherlou, Masoud Nouri-Vaskeh, Sama Noroozi Guilandehi, Amir Baghbanzadeh, Ramin Zand, Behzad Baradaran, Mohammad Zarei
Summary: GDF-15 plays a complex role in cancer, with both tumor-suppressive and oncogenic effects, and its impact on tumor development is linked to the type and stage of cancer.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Wouter H. G. Hubens, Marielle T. Kievit, Tos T. J. M. Berendschot, Irenaeus F. M. de Coo, Hubert J. M. Smeets, Carroll A. B. Webers, Theo G. M. F. Gorgels
Summary: Plasma GDF-15 was evaluated as a biomarker for mitochondrial dysfunction in OAG patients, but no significant differences were found after correcting for confounders. Age, gender, smoking, and systemic hypertension were identified as significant confounders affecting GDF-15 levels. Subgroup analysis showed no correlation between disease severity and plasma GDF-15, but NTG patients taking dietary supplements had lower GDF-15 levels.
Article
Multidisciplinary Sciences
Ming Yang, Tamana Darwish, Pierre Larraufie, Debra Rimmington, Irene Cimino, Deborah A. Goldspink, Benjamin Jenkins, Albert Koulman, Cheryl A. Brighton, Marcella Ma, Brian Y. H. Lam, Anthony P. Coll, Stephen O'Rahilly, Frank Reimann, Fiona M. Gribble
Summary: Recent studies have found that the gastrointestinal tract is an important site of action for metformin, affecting glucose uptake, glycolysis, and GDF-15 secretion likely due to observed mitochondrial dysfunction. These findings help explain the effects of metformin on intestinal glucose utilization and food balance.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Seok Woo Hong, Jeong-Hyun Kang
Summary: This study aims to investigate the potential role of GDF-15 in bone metabolism and muscle function in females with osteoporosis. The results showed that serum levels of GDF-15 were higher in participants with osteoporosis compared to healthy/osteopenic participants. The mRNA levels of GDF-15, IL-1β, and TNF-α in muscle were significantly higher in the osteoporotic group. GDF-15 may have associations with bone metabolism and muscle homeostasis through paracrinological and endocrinological mechanisms.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Medicine, Research & Experimental
Qing-Ao Xiao, Qian He, Jun Zeng, Xuan Xia
Summary: Growth and differentiation factor 15 (GDF-15), a member of the TGF-beta superfamily, has been found to be significantly correlated with glucolipid metabolic disorders and cardiovascular diseases. The recently discovered receptor GFRAL has been shown to regulate energy homeostasis and have positive effects on appetite suppression, metabolic enhancement, and vascular remodeling. Therefore, GDF-15 holds potential as a therapeutic target for glucolipid metabolic disorders and vascular diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Immunology
Darakhshan Sohail Ahmed, Stephane Isnard, Carolina Berini, John Lin, Jean-Pierre Routy, Lena Royston
Summary: Growth differentiation factor 15 (GDF-15) is a cytokine that plays a crucial role in regulating metabolism. It is produced in response to mitochondrial stress, tissue damage, or hypoxia, and is considered one of the strongest predictors of disease severity in inflammatory conditions, cancers, and infections. Although the exact mechanisms are still unclear, GDF-15 is believed to have tissue-protective effects through sympathetic and metabolic adaptation in the context of mitochondrial damage. This review discusses the emergence of GDF-15 as a distinct marker of viral infection severity, particularly in the context of COVID-19. It critically evaluates the role of GDF-15 as an inflammation-induced mediator of disease tolerance, involving metabolic and immune reprogramming. The review also explores potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Overall, GDF-15 appears to be involved in disease tolerance to viral infections, including SARS-CoV-2, and may serve as a target for novel therapeutic interventions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Shuai Zheng, Min Shen, Yu Qian, Shushu Li, Yang Chen, Hemin Jiang, Hui Lv, Doudou Chen, Ruiling Zhao, Xuqin Zheng, Min Sun, Tao Yang, Yun Shi, Qi Fu
Summary: This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio as biomarkers for detecting metabolic syndrome. The results suggest that the G/A ratio and adiponectin are potential biomarkers for detecting metabolic syndrome in women and men, respectively.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Justin B. Echouffo-Tcheugui, Natalie Daya, Chiadi E. Ndumele, Kunihiro Matsushita, Ron C. Hoogeveen, Christie M. Ballantyne, Josef Coresh, Amil M. Shah, Elizabeth Selvin
Summary: In a community-based sample of US adults, elevated GDF-15 levels were more common in individuals with diabetes compared to those without diabetes. GDF-15 was independently associated with heart failure (HF) in both groups, with a stronger association among individuals with diabetes. Individuals with diabetes and elevated GDF-15 had the highest risk of incident HF. GDF-15 provided additional prognostic information for HF risk, especially among individuals with diabetes.
Correction
Cardiac & Cardiovascular Systems
Yong Wang, Felix Polten, Felix Jackle, Mortimer Korf-Klingebiel, Tibor Kempf, Johann Bauersachs, Sandra Freitag-Wolf, Ralf Lichtinghagen, Andreas Pich, Kai C. Wollert
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Jonas Neuser, Tibor Kempf, Johann Bauersachs, Julian D. Widder
Summary: The study demonstrates that the ALLEGRA valve provides excellent hemodynamic results and a good safety profile with a low complication rate in patients treated for aortic valve stenosis or degenerated valve prosthesis.
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
(2022)
Letter
Cardiac & Cardiovascular Systems
Tobias Koenig, Tibor Kempf, Heinz-Peter Schultheiss, Markus Cornberg, Johann Bauersachs, Andreas Schaefer
CLINICAL RESEARCH IN CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Stephan von Haehling, Christoph Birner, Elke Dworatzek, Stefan Frantz, Kristian Hellenkamp, Carsten W. Israel, Tibor Kempf, Hermann H. Klein, Christoph Knosalla, Ulrich Laufs, Philip Raake, Rolf Wachter, Gerd Hasenfuss
Summary: Patients with heart failure face a higher risk of cardiovascular events during travel and should adhere to specific recommendations to lower this risk. Factors to consider when choosing a travel destination include distance, season, air pollution, jet lag, and altitude, as they can increase the risk of symptom development. Pre-travel risk assessment and advice on preventing illness and volume depletion should be provided to patients. Special considerations are needed for patients with cardiac implantable electronic devices or recent cardiac surgery.
NATURE REVIEWS CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Valentin G. Hirsch, Sven Schallhorn, Carolin Zwadlo, Johanna Diekmann, Florian Langer, Danny David Jonigk, Tibor Kempf, Heinz-Peter Schultheiss, Johann Bauersachs
Summary: This case report describes a young man who was admitted to the Department of Cardiology and Angiology at Hannover Medical School with symptoms of shortness of breath and elevated troponin. After being diagnosed with giant cell myocarditis and having received the first dose of BioNTech's mRNA vaccine, the patient was treated with immunosuppressive therapy. The article discusses this rare etiology of myocarditis following mRNA vaccination and the treatment strategy employed in this particular case according to current recommendations.
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Article
Cardiac & Cardiovascular Systems
Faisal Sharif, Stephen Rosenkranz, Jozef Bartunek, Tibor Kempf, Birgit Assmus, Niall G. Mahon, Wilfried Mullens
Summary: This study evaluated the safety and efficacy of a novel wireless pulmonary artery pressure monitoring system in patients with heart failure. The results showed that the system had excellent safety and equivalence with standard right heart catheterization for mean pulmonary artery pressures, allowing for comprehensive management of heart failure patients.
Article
Cardiac & Cardiovascular Systems
Tibor Kempf, Udo Bavendiek
Summary: The current guidelines recommend early and simultaneous use of multiple drug classes for the pharmacotherapy of heart failure, including beta-blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, ACE inhibitors or angiotensin receptor neprilysin inhibitors. The choice of drugs and dosage may vary based on individual patient characteristics and comorbidities.
AKTUELLE KARDIOLOGIE
(2022)
Article
Cardiac & Cardiovascular Systems
Eri Toda Kato, David A. Morrow, Jianping Guo, David D. Berg, Michael A. Blazing, Erin A. Bohula, Marc P. Bonaca, Christopher P. Cannon, James A. de Lemos, Robert P. Giugliano, Petr Jarolim, Tibor Kempf, L. Kristin Newby, Michelle L. O'Donoghue, Marc A. Pfeffer, Nader Rifai, Stephen D. Wiviott, Kai C. Wollert, Eugene Braunwald, Marc S. Sabatine
Summary: Levels of growth differentiation factor 15 (GDF-15) have been associated with various cardiovascular events. This study analyzed data from eight trials and found that higher GDF-15 concentration was independently associated with increased rates of cardiovascular death/hospitalization for heart failure and major adverse cardiovascular events. However, the prognostic association of GDF-15 with future myocardial infarction and stroke remained significant only in patients stabilized after recent acute coronary syndrome or with stable atherosclerotic cardiovascular disease, not in acute coronary syndrome patients.
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Gorav Batra, Johan Lindback, Richard C. Becker, Robert A. Harrington, Claes Held, Stefan K. James, Tibor Kempf, Renato D. Lopes, Kenneth W. Mahaffey, Philippe Gabriel Steg, Robert F. Storey, Eva Swahn, Kai C. Wollert, Agneta Siegbahn, Lars Wallentin
Summary: This study developed a biomarker-based prediction model for predicting the 1-year risk of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). The model showed good calibration and discrimination in both the development cohort and the validation cohort.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Alice Rovai, BoMee Chung, Qingluan Hu, Sebastian Hook, Qinggong Yuan, Tibor Kempf, Florian Schmidt, Dirk Grimm, Steven R. Talbot, Lars Steinbrueck, Jasper Goetting, Jens Bohne, Simon A. Krooss, Michael Ott
Summary: This study demonstrates that a single administration of AAV8 vectors expressing an Adenine Base Editor can efficiently correct genes in hepatocytes, leading to improvement in iron-specific parameters in the liver and blood of mouse models with Hemochromatosis. This provides proof-of-concept for targeted gene correction therapy for one of the most common hereditary diseases.
NATURE COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Bomee Chung, Yong Wang, Marleen Thiel, Fatemeh Rostami, Anika Rogoll, Valentin G. Hirsch, Zulaikha Malik, Anne Buehrke, Christian Baer, Michael Klintschar, Jan D. Schmitto, Carla Vogt, Christopher Werlein, Danny Jonigk, Johann Bauersachs, Kai C. Wollert, Tibor Kempf
Summary: This study aims to investigate the functional importance of cardiac iron status after myocardial infarction (MI) and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling. The results showed that cardiac iron status was dynamically regulated after MI, and iron supplementation could maintain cardiac iron content and attenuate adverse remodeling. These findings suggest that cardiac iron deficiency is a novel disease mechanism and therapeutic target in post-infarction LV remodeling and HF.
CARDIOVASCULAR RESEARCH
(2023)
Article
Medicine, Research & Experimental
Keisuke Shirakura, Peter Baluk, Astrid F. Nottebaum, Ute Ipe, Kevin G. Peters, Donald M. McDonald, Dietmar Vestweber
Summary: Vascular endothelial protein tyrosine phosphatase (VE-PTP) affects endothelial barrier function by regulating Tie2 activation. High shear stress caused VE-PTP polarization and endocytosis, along with Tie2 activation, in regions with smooth flow. In regions with disturbed flow, VE-PTP remained associated with Tie2. Endothelial cells exposed to high shear stress had increased Tie2 activation and reduced macromolecular permeability. Deleting VE-PTP or inhibiting it with AKB-9785 had similar anti-atherogenic effects.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Josephine A. Mapunda, Javier Pareja, Mykhailo Vladymyrov, Elisa Bouillet, Pauline Helie, Petr Pleskac, Sara Barcos, Johanna Andrae, Dietmar Vestweber, Donald M. Mcdonald, Christer Betsholtz, Urban Deutsch, Steven T. Proulx, Britta Engelhardt
Summary: This study reveals the junctional localization of VE-cadherin in arachnoid and pia mater cells, which can be used as an informative landmark for in vivo imaging of the leptomeninges and their potential barrier properties.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Peter Baluk, Keisuke Shirakura, Dietmar Vestweber, Donald M. Mcdonald
Summary: Endothelial cells of mammalian blood vessels exhibit multiple levels of heterogeneity along the vascular tree and among different organs, and further heterogeneity is caused by blood flow turbulence and variations in shear stress. This study discovered new levels of functional mosaicism in the endothelial cells of the aorta and vena cava, where blood flow dynamics are known to be heterogeneous.
CELL AND TISSUE RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Helge Moellmann, Ralph Stephan von Bardeleben, Henryk Dreger, Joerg Hausleiter, Tibor Kempf, Edith Lubos, Philipp Lurz, Holger Nef, Georg Nickenig, Philip Raake, Christian Opitz, Volker Rudolph, Hendrik Schmidt, P. Christian Schulze, Stephan Baldus
Summary: Patients with high-grade tricuspid valve insufficiency require precise characterization and interdisciplinary discussion for appropriate treatment. Catheter-based intervention plays an important role, but further research and standardization are needed due to the complexity and challenges involved.