Editorial Material
Immunology
Pin Li, Napoleone Ferrara
Summary: This study reveals the crosstalk between VEGF receptors in different organs and emphasizes the importance of VEGF receptor expression and interplay in vascular heterogeneity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Obstetrics & Gynecology
Jessica R. Zolton, Lindsey A. Sjaarda, Sunni L. Mumford, Elizabeth A. DeVilbiss, Keewan Kim, Kerry S. Flannagan, Jeannie G. Radoc, Neil J. Perkins, Robert M. Silver, Jean Wactawski-Wende, Micah J. Hill, Alan H. DeCherney, Enrique F. Schisterman
Summary: Circulating VEGF and sFLT-1 did not vary significantly across the menstrual cycle in normal ovulating women, and may not be useful as peripheral biomarkers of endometrial changes during the menstrual cycle. Plasma may be the preferred medium for measuring circulating VEGF in reproductive-age women, regardless of menstrual cycle phase.
OBSTETRICS AND GYNECOLOGY
(2021)
Article
Biology
Yiting Zhang, Jianping Hu, Xiaoying Qu, Ke Hu
Summary: The circular RNA circRSU1 is upregulated in diabetic retinopathy patients and its interaction with miR-345-3p leads to increased TAZ levels, which contribute to the development of vascular dysfunction. Diabetic retinopathy is a major cause of visual impairment and blindness in adults with diabetes mellitus. Although circRNAs have been implicated in vascular progression, the exact role of circRNAs in diabetes-induced vascular complications remains largely unknown. The authors found that circRSU1 was significantly upregulated in diabetic retinopathy patients. Further experiments showed that knockdown of circRSU1 alleviated diabetes-induced retinal vascular dysfunction, including decreased levels of vascular endothelial growth factor, reduced inflammatory responses, and diminished oxidative stress. The study also revealed that circRSU1 interacts with miR-345-3p to upregulate TAZ expression, and downregulation of TAZ reversed the vascular dysfunction caused by increased circRSU1 expression under high glucose conditions. In conclusion, the overexpression of circRSU1 promotes vascular dysfunction through its interaction with miR-345-3p to increase TAZ levels in diabetic conditions. The findings suggest that circRSU1 may serve as a potential therapeutic target for treating vascular dysfunction in diabetes mellitus.
COMMUNICATIONS BIOLOGY
(2023)
Review
Peripheral Vascular Disease
Ferdinand A. C. le Noble, Jean-Jacques Mourad, Bernard I. Levy, Harry A. J. Struijker-Boudier
Summary: Drugs inhibiting VEGF have been widely used in cancer treatment, but they often cause cardiovascular side effects, with hypertension being the most frequently observed. This review explores the mechanism behind VEGF inhibitor-induced hypertension, focusing on microvascular rarefaction, which is supported by evidence from experimental and clinical studies.
Article
Biochemistry & Molecular Biology
Annika Schulz, Carolin Christina Drost, Bettina Hesse, Katrin Beul, Marcus Brand, Giovana Seno Di Marco
Summary: sFlt-1 has damaging effects on endothelial cell structure and function. Its levels are correlated with endothelial cell cortex stiffening, which is accompanied by cytoskeleton reorganization and changes in endothelial barrier function, mediated by p38 MAPK activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Daria Monogiou Belik, Riccardo Bernasconi, Lifen Xu, Giacomo Della Verde, Vera Lorenz, Vivienne Gruterich, Melania Balzarolo, Michika Mochizuki, Otmar Pfister, Gabriela M. Kuster
Summary: This study aimed to test whether Flt3-targeting TKI treatment aggravates cardiac injury after myocardial infarction (MI). The results showed that quizartinib did not alter cardiac dimensions or function in healthy mice, but significantly enhanced ventricular dilatation and apoptotic cell death in MI mice. In vitro studies further confirmed that quizartinib increased cell death and apoptosis, potentially through a p38-dependent mechanism.
Review
Peripheral Vascular Disease
Andrew C. Dudley, Arjan W. Griffioen
Summary: Angiogenesis, the formation of new blood vessels, plays a crucial role in growth and development. However, in pathological conditions, this process becomes dysregulated, presenting new challenges and opportunities for vascular-directed therapies. This review provides insights into blood vessel development and discusses novel therapeutic strategies to stabilize, reverse or halt disease progression by promoting or inhibiting angiogenesis. The review also explores additional aspects that operate alongside canonical angiogenesis mechanisms and speculates on targeting these processes with anti-angiogenic or vascular-directed therapies.
Article
Biochemistry & Molecular Biology
Annika Schulz, Carolin C. Drost, Bettina Hesse, Katrin Beul, Goeran R. Boeckel, Alexander Lukasz, Hermann Pavenstaedt, Marcus Brand, Giovana S. Di Marco
Summary: In this study, it was found that excess sFlt-1 led to conformational changes in the endothelial glycocalyx (eGC), resulting in increased monocyte adhesion and vascular dysfunction. The eGC became flat and stiff under excess sFlt-1, while its structural components remained unchanged. Functionally, this conformation increased endothelial adhesiveness to THP-1 monocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Typhaine Anquetil, Romain Solinhac, Aude Jaffre, Gaetan Chicanne, Julien Viaud, Jean Darcourt, Cyrille Orset, Eva Geuss, Christoph Kleinschnitz, Bart Vanhaesebroeck, Denis Vivien, Karim Hnia, Vincent Larrue, Bernard Payrastre, Marie-Pierre Gratacap
Summary: Protecting endothelial cells is critical in preventing the impact of vascular leakage and edema on pathological conditions. PI3KC2 beta could be a potential new therapeutic target for treating aggravating lesions following ischemic stroke.
Article
Pharmacology & Pharmacy
Zuoquan Zhu, Jiahang Song, Junjie Gu, Bing Xu, Xinchen Sun, Shu Zhang
Summary: FL enhances the radioresistance of esophageal squamous cell carcinoma cells through promoting clone formation, increasing EdU incorporation, enhancing DNA damage repair, and inhibiting apoptosis. The significantly increased expression of Flt-3 receptor in ESCC cells after radiation may play a key role in their radioresistance.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Piotr Kobialka, Helena Sabata, Odena Vilalta, Leonor Gouveia, Ana Angulo-Urarte, Laia Muixi, Jasmina Zanoncello, Oscar Munoz-Aznar, Nagore G. Olaciregui, Lucia Fanlo, Anna Esteve-Codina, Cinzia Lavarino, Biola M. Javierre, Veronica Celis, Carlota Rovira, Susana Lopez-Fernandez, Eulalia Baselga, Jaume Mora, Sandra D. Castillo, Mariona Graupera
Summary: This study demonstrates the importance of the PI3K/AKT pathway in low-flow vascular malformations and establishes a model to study and test molecular therapies for this disease. The results show that the AKT inhibitor miransertib can prevent and induce regression of PI3K-driven vascular malformations, suggesting its potential therapeutic role for these diseases.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Jungwhoi Lee, Kyuha Chong, Jungsul Lee, Chungyeul Kim, Jae-Hoon Kim, Kyungsun Choi, Chulhee Choi
Summary: This study identified the non-classical function of neuropilin-1 (NRP-1) expression in human glioblastoma (GB) and its association with vascular endothelial growth factor (VEGF)-A signaling. Different sensitivity to VEGF-A signaling resulted in distinct NRP-1 expression patterns, which were correlated with prognosis.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Review
Cell Biology
Mabruka Alfaidi, Matthew L. Scott, Anthony Wayne Orr
Summary: The Nck family of adaptor proteins, Nck1 and Nck2, play crucial roles in linking phosphotyrosine signaling to changes in cytoskeletal dynamics and gene expression, affecting cellular phenotype. While they have redundant roles in vascular development and angiogenesis, recent studies suggest that Nck1 and Nck2 may differentially regulate cell phenotype in the adult vasculature. Domain-specific interactions likely mediate these isoform-selective effects, and could potentially be targeted for therapeutic interventions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemical Research Methods
Jessica R. Crawshaw, Jennifer A. Flegg, Miguel O. Bernabeu, James M. Osborne
Summary: This review article examines the existing mathematical models of developmental vascular remodelling and discusses their contributions to the field of vascular development. It identifies four modelling paradigms and addresses future directions for each paradigm. The development of multiscale models, subcellular models, and experimental model validation are identified as major challenges for the field moving forward.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Review
Oncology
Emmy D. G. Fleuren, Myrella Vlenterie, Winette T. A. van der Graaf
Summary: Osteosarcoma (OS) and Ewing sarcoma (ES) are two common types of primary bone cancer that mainly affect young people. Despite aggressive treatment, survival rates have not significantly improved in the past four decades. Clinical efficacy has been observed with some mono-Receptor Tyrosine Kinase (RTK) inhibitors, but only in small subsets of patients. Newer generation multi-RTK inhibitors have shown efficacy in larger groups of OS or ES patients. However, registration for these indications has not been obtained, making it difficult to implement these drugs in routine patient care.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Paul Cheng, Robert C. Wirka, Lee Shoa Clarke, Quanyi Zhao, Ramendra Kundu, Trieu Nguyen, Surag Nair, Disha Sharma, Hyun-jung Kim, Huitong Shi, Themistocles Assimes, Juyong Brian Kim, Anshul Kundaje, Thomas Quertermous
Summary: This study identifies ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.
Article
Developmental Biology
Wenguang Yin, Andreas Liontos, Janine Koepke, Maroua Ghoul, Luciana Mazzocchi, Xinyuan Liu, Chunyan Lu, Haoyu Wu, Athanasios Fysikopoulos, Alexandros Sountoulidis, Werner Seeger, Clemens Ruppert, Andreas Gunther, Didier Y. R. Stainier, Christos Samakovlis
Summary: The tracheal epithelium is a crucial element in pulmonary diseases, and its understanding of cell proliferation and differentiation is limited. The Hedgehog (HH) signaling pathway plays a role in communication between epithelial and mesenchymal cells in the lung, affecting stromal cell proliferation, differentiation, and epithelial signaling. This study discovered an autocrine HH signaling function in airway epithelial cells, with its inhibition leading to defects in cell proliferation and differentiation. Additionally, HH function is mediated by transcriptional activation, as inhibition of HH signaling downregulates cell type-specific transcription factor genes in both mouse trachea and human airway epithelial cells. These findings provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Article
Cardiac & Cardiovascular Systems
Muhammad Fazal, Ridhima Kapoor, Paul Cheng, Albert J. Rogers, Sanjiv M. Narayan, Paul Wang, Ronald M. Witteles, Alexander C. Perino, Tina Baykaner, June-Wha Rhee
Summary: In patients on ibrutinib therapy, there is a high prevalence of atrial and ventricular arrhythmias, leading to treatment interruption and the need for antiarrhythmic drugs.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Environmental Sciences
Marco Tarasco, Paulo J. Gavaia, Anabela Bensimon-Brito, Fabrice P. Cordelieres, Tamara Santos, Gil Martins, Daniela T. de Castro, Nadia Silva, Elsa Cabrita, Maria J. Bebianno, Didier Y. R. Stainier, M. Leonor Cancela, Vincent Laize
Summary: The presence of microplastics in the aquatic ecosystem poses a major problem for the environment and human health. The capacity of organic pollutants to adsorb onto microplastic particles raises concerns, as it provides a new route for toxic compounds to enter the food web. This study provides new insights into the biological effects of pristine and/or contaminated microplastics on zebrafish.
Article
Cell Biology
Giulia L. M. Boezio, Shengnan Zhao, Josephine Gollin, Rashmi Priya, Shivani Mansingh, Stefan Guenther, Nana Fukuda, Felix Gunawan, Didier Y. R. Stainier
Summary: The epicardium, the outermost layer of the heart, plays an important role in regulating cardiac regeneration. This study investigated the interaction between the epicardium and myocardium during development by creating three models of epicardial impairment in zebrafish. The results showed that the epicardium is required for cardiomyocyte growth during early cardiac morphogenesis and identified FGF and VEGF signaling pathways as important regulators of ventricular growth.
DISEASE MODELS & MECHANISMS
(2023)
Review
Cardiac & Cardiovascular Systems
Muhammad Fazal, Chen Wei, Katherine Lee Chuy, Kifah Hussain, Sofia E. Gomez, Shayena Shah Ba, Grzegorz Pietrasik, Neha Yadav, Zaniar Ghazizadeh, Ridhima Kapoor, Ronald M. Witteles, Amanda Blackmon, Paul J. Wang, Roy M. John, Sanjiv M. Narayan, Paul Cheng, June-Wha Rhee, Tina Baykaner
Summary: This study described five detailed cases of ventricular arrhythmias (VAs) related to tyrosine kinase inhibitor (TKI) use in patients with varied cardiovascular risk factors. The study found that all patients had significant improvement in VA burden after cessation of TKI therapy, but two patients required long-term antiarrhythmic drug therapy and one patient had an implantable defibrillator cardioverter (ICD) placed. The authors emphasized the need to acknowledge the association between TKIs and cardiovascular complications and to deploy preventive and therapeutic measures.
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Thomas Juan, Agatha Ribeiro da Silva, Barbara Cardoso, SoEun Lim, Violette Charteau, Didier Y. R. Stainier
Summary: Cardiac valves play a vital role in ensuring unidirectional blood flow through the heart. Researchers have identified several mechanosensory genes as key regulators of valve development, expanding our understanding of this process.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lavinia Arseni, Rakesh Sharma, Norman Mack, Deepthi Nagalla, Sibylle Ohl, Thomas Hielscher, Mahak Singhal, Robert Pilz, Hellmut Augustin, Roger Sandhoff, Christel Herold-Mende, Bjoern Tews, Peter Lichter, Martina Seiffert
Summary: A better understanding of tumor-stroma crosstalk and the role of sphingosine-1-phosphate (S1P) in mediating this crosstalk is crucial for the development of therapeutic approaches for human glioma. This study shows that higher levels of S1P result in an anti-inflammatory environment and inhibition of S1P signaling improves the anti-tumor response and overall survival in glioblastoma. These findings highlight the potential of targeting S1P as a therapeutic strategy.
Article
Cardiac & Cardiovascular Systems
Huitong Shi, Trieu Nguyen, Quanyi Zhao, Paul Cheng, Disha Sharma, Hyun-Jung Kim, Juyong Brian Kim, Robert Wirka, Chad S. Weldy, Joao P. Monteiro, Thomas Quertermous
Summary: In this study, deep transcriptome sequencing of human coronary artery smooth muscle cells (SMCs) revealed 4579 known and 13655 de novo long noncoding RNAs (lncRNAs). These lncRNAs were found to be enriched near CAD-related transcription factors, genetic loci, and gene regulators of SMC identity. Two novel lncRNAs, ZIPPOR and TNS1-AS2, were identified to exert their function in SMC phenotypic transition through the CAD gene ZEB2.
CIRCULATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hyun-Jung Kim, Paul Cheng, Stanislao Travisano, Chad Weldy, Joao P. Monteiro, Ramendra Kundu, Trieu Nguyen, Disha Sharma, Huitong Shi, Yi Lin, Boxiang Liu, Saptarsi Haldar, Simon Jackson, Thomas Quertermous
Summary: Genes encoding risk for coronary disease are crucial for developing new therapies. A particular gene, PDGFD, has been identified as a culprit gene and it promotes disease risk. Mechanistic studies confirm that rs2019090 and PDGFD represent the functional genetic variant and gene responsible for coronary artery disease. PDGFD mediates CAD risk by promoting deleterious phenotypic changes in smooth muscle cells and an inflammatory response primarily focused in the adventitia.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Melina Hussmann, Dorte Schulte, Sarah Weischer, Claudia Carlantoni, Hiroyuki Nakajima, Naoki Mochizuki, Didier Y. R. Stainier, Thomas Zobel, Manuel Koch, Stefan Schulte-Merker, Victoria L. Bautch
Summary: This study reveals the critical roles of Svep1 and Tie1 in the development of specific subpopulations of the zebrafish facial lymphatic network. It also shows that this aspect of the network is formed independently of Vegfc signaling. The findings demonstrate the importance of Tie1 signaling in lymphangiogenesis and blood vessel development in zebrafish.
Article
Cardiac & Cardiovascular Systems
Albert J. Pedroza, Paul Cheng, Alex R. Dalal, Kathrin Baeumler, Aya Kino, Emily Tognozzi, Rohan Shad, Nobu Yokoyama, Ken Nakamura, Olivia Mitchel, William Hiesinger, Elena Gallo Macfarlane, Dominik Fleischmann, Y. Joseph Woo, Thomas Quertermous, Michael P. Fischbein
Summary: Patients with Loeys-Dietz syndrome who undergo prophylactic aortic arch replacement during valve-sparing aortic root replacement demonstrate excellent surgical outcomes without overt downstream flow or shear stress disturbances. Abnormal smooth muscle cell-mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Review
Physiology
Stephanie F. Preuss, Denise Grieshober, Hellmut G. Augustin
Summary: Proliferating cancer cells secrete factors that impact metabolism, interorgan communication, and tumor progression. These factors modulate endothelial cell activation, affecting tumor cell dissemination and the outgrowth of metastatic cells. Furthermore, endothelial cell signaling is involved in cancer-related metabolic symptoms, opening a new field of research. This review explores how these tumor-derived factors systemically affect endothelial cell signaling, activation, and impact distant organs as well as tumor progression.
Article
Genetics & Heredity
Jordan M. Welker, Vahan Serobyan, Elhamalsadat Zaker Esfahani, Didier Y. R. Stainier
Summary: Transcriptional adaptation (TA) is a mechanism that modulates gene expression in response to mutations in mRNA. Researchers found a 25-base pair element in the regulatory region of the adapting gene that showed similarity to a sequence in the mutant mRNA. This element can induce ectopic expression of a fluorescent reporter gene, indicating its importance in TA.
Article
Cardiac & Cardiovascular Systems
Chen Wei, Muhammad Fazal, Alexander Loh, Ridhima Kapoor, Sofia Elena Gomez, Shayena Shah, Albert J. J. Rogers, Sanjiv M. M. Narayan, Paul J. J. Wang, Ronald M. M. Witteles, Alexander C. C. Perino, Paul Cheng, June-Wha Rhee, Tina Baykaner
Summary: This study compared the arrhythmia burden in patients receiving ibrutinib, non-BTK TKIs, or non-TKI therapies. The results showed that patients receiving ibrutinib had a higher prevalence of atrial fibrillation and non-sustained ventricular tachycardia, and a higher rate of treatment interruption due to arrhythmias.
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
(2023)