Review
Biochemistry & Molecular Biology
Wa Du, Lu Ren, Milton H. Hamblin, Yanbo Fan
Summary: The process of angiogenesis, involving the formation of new blood vessels from existing ones, is critical in various physiological and pathological conditions. Endothelial cell metabolism, particularly glycolysis, has been shown to play a significant role in angiogenesis, with various regulators identified to modulate this process. Understanding the metabolic regulation in endothelial cells could lead to potential therapeutic strategies for angiogenesis-related diseases.
Article
Cell Biology
Carolina Venturoli, Ilaria Piga, Matteo Curtarello, Martina Verza, Giovanni Esposito, Santina Venuto, Filippo Navaglia, Angela Grassi, Stefano Indraccolo
Summary: The blockade of Pyruvate dehydrogenase kinase 1 (PDK1) triggers significant metabolic alterations in cancer cells, leading to reduced glycolysis and increased glucose oxidation. In a study investigating the effects of PDK1 silencing on tumor xenografts formed by highly glycolytic ovarian cancer cells, it was found that PDK1 silencing had a dramatic negative impact on tumor growth, associated with reduced angiogenesis and increased necrosis. Furthermore, PDK1-silenced tumors showed increased proliferation, apoptosis, and glucose catabolic pathways, suggesting a link between tumor metabolism and angiogenesis.
Review
Biochemistry & Molecular Biology
Chaithanya Chelakkot, Vipin Shankar Chelakkot, Youngkee Shin, Kyoung Song
Summary: Cancer cells undergo metabolic reprogramming to adopt a glycolysis-dominant metabolic profile, providing them with a survival advantage and contributing to a pro-cancerous tumor environment. This metabolic switch also leads to increased resistance to chemotherapy and radiation. Immune cells in the tumor microenvironment also exhibit a similar metabolic shift, leading to competition with cancer cells for nutrients. Targeting enhanced glycolysis in cancer cells has shown promise in improving treatment efficacy, but effective strategies are still lacking. This review highlights the importance of metabolic reprogramming in cancer cells and the potential of targeting it to enhance conventional cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Zi-Yi Zhou, Lin Wang, Yu-Sheng Wang, Guo-Rui Dou
Summary: The current treatment for ocular pathological angiogenesis focuses on anti-VEGF signals, but regulation of endothelial glycolysis has emerged as a potential treatment targeting vessel sprouting.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Qian Cheng, Xiao-Lei Shi, Qi-Lin Li, Lin Wang, Zheng Wang
Summary: Numerous studies have shown that nanomaterials can modulate lactate metabolism to enhance anti-tumor therapy.
Review
Medicine, Research & Experimental
Sai-li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
Summary: Although most thyroid cancer patients can be cured with existing treatments, options for patients with poorly differentiated or radioiodine-refractory thyroid cancer are limited. Thyroid cancer cells undergo metabolic reprogramming to meet their energy demands and support malignant behaviors. This review summarizes advances in understanding the reprogramming of glucose metabolism in thyroid cancer cells, aiming to identify new therapeutic approaches for specific types of thyroid cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Rafael Agustin Burgos, Pablo Alarcon, John Quiroga, Carolina Manosalva, Juan Hancke
Summary: Andrographolide, the main active ingredient isolated from Andrographis paniculata, possesses diverse biological effects including anti-inflammatory, antioxidant, and antineoplastic properties. Its targets include transcription factors NF-kappa B, AP-1, and HIF-1, as well as signaling pathways such as PI3K/Akt, MAPK, and JAK/STAT. The increase in Nrf2 signaling pathway supports its antioxidant and anti-inflammatory properties, while recent evidence suggests that andrographolide may modulate glucose metabolism, potentially explaining its diverse therapeutic effects.
Review
Chemistry, Multidisciplinary
Bicai Tang, Wenjuan Ma, Yunfeng Lin
Summary: Studies have shown the potential of nanomaterials in inhibiting pathological angiogenesis, providing new options for cancer treatment. Compared to traditional anti-angiogenic agents, nanomaterials have better targeting capabilities and therapeutic outcomes, reducing side effects.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Engineering, Biomedical
Xing-Lan Ding, Miao-Deng Liu, Qian Cheng, Wen-Hui Guo, Mei-Ting Niu, Qian-Xiao Huang, Xuan Zeng, Xian-Zheng Zhang
Summary: This study designed a tumor acidity-responsive nanoparticle that combines ATP generation inhibition and photothermal therapy to enhance tumor treatment. By inhibiting glycolysis and increasing oxidative stress, the nanoparticles degrade and cause mitochondrial dysfunction, leading to reduced ATP production and heat shock protein expression, ultimately improving the therapeutic effect of photothermal therapy.
Review
Cell Biology
Yun Liu, Nenggan Huang, Shijie Liao, Emel Rothzerg, Felix Yao, Yihe Li, David Wood, Jiake Xu
Summary: Osteosarcoma is the most common primary malignant bone tumor, with incidence peaking during adolescence. Despite improvements in prognosis with the introduction of neoadjuvant chemotherapy, outcomes have not significantly improved since then. Novel therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for patients with osteosarcoma.
CELL PROLIFERATION
(2021)
Review
Nutrition & Dietetics
Zhenhua Zeng, Qiaobing Huang, Liangfeng Mao, Jie Wu, Sheng An, Zhongqing Chen, Weijin Zhang
Summary: Anaerobic glycolysis is the primary metabolic pathway in sepsis, and the PDHC complex plays a crucial role in energy metabolism. Activation of PDHC can regulate lactate balance, inflammatory mediator release, and improve energy metabolism. Therapeutic drugs targeting PDHC activation for sepsis treatment include dichloroacetate, thiamine, and others.
FRONTIERS IN NUTRITION
(2021)
Review
Oncology
Qing Li, Xiao Gui, Haorui Zhang, Weiye Zhu, Rui Zhang, Wei Shen, Hongyuan Song
Summary: Glucose metabolism plays a crucial role in maintaining cell function and homeostasis, as well as regulating angiogenesis. Ocular vascular diseases are common and their prevalence is increasing. Understanding intercellular communication and the role of glucose metabolism in angiogenesis is important for treating ocular vascular diseases.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Biotechnology & Applied Microbiology
Tiffany S. Nelson, Chiab Simpson, Frank Dyka, Astra Dinculescu, W. Clay Smith
Summary: Glucose metabolism in the retina is carefully regulated, with glucose being delivered to photoreceptors from the choroidal circulation. This study investigates the use of a modified protein called ArrGG to increase lactate production and slow down retinal degeneration. Overexpression of ArrGG in mouse retinas resulted in an increase in lactate secretion, while in a mouse model of retinitis pigmentosa, the expression of ArrGG led to significant preservation of photoreceptor function and slowing of retinal degeneration. These findings suggest that enhancing glycolysis may offer a therapeutic approach to slow down retinal degeneration.
HUMAN GENE THERAPY
(2022)
Review
Oncology
Zhengyang Yang, Wei Deng, Xiao Zhang, Yongbo An, Yishan Liu, Hongwei Yao, Zhongtao Zhang
Summary: Digestive tumours are a common type of malignancy that have led to the highest number of tumour-related deaths. Abnormal angiogenesis, the formation of new blood vessels, plays a crucial role in the growth, progression, and metastasis of these tumours. Traditional anti-angiogenic therapies have limitations and resistance issues, but nanotechnology-based therapies using nanoparticles show promise in targeted drug delivery and increased drug bioavailability. This review outlines the mechanisms of angiogenesis, the effects of nanoparticles on angiogenesis, and their biomedical applications in digestive tumours.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Yi Zhang, Qiong Li, Zhao Huang, Bowen Li, Edouard C. Nice, Canhua Huang, Liuya Wei, Bingwen Zou
Summary: Reprogramming glucose metabolism is an important strategy for targeted cancer treatment. Although advanced and effective drugs have been developed, there are still challenges in translating them into clinical applications due to limitations such as short half-life, poor solubility, and multiple side effects. Combining glucose metabolism modulators with conventional anticancer drugs may be a future direction for cancer treatment.
Review
Cardiac & Cardiovascular Systems
Lisa M. Becker, Shiau-Haln Chen, Julie Rodor, Laura P. M. H. de Rooij, Andrew H. Baker, Peter Carmeliet
Summary: Endothelial cells play a crucial role in the human body but their heterogeneity poses challenges in therapy. Recent studies have revealed the diverse functions of endothelial cells and their roles in diseases, and proposed strategies to deal with this heterogeneity.
CARDIOVASCULAR RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Jie Li, Yan Zhou, Guy Eelen, Qing-tong Zhou, Wen-bo Feng, Viktorija Labroska, Fen-fen Ma, Hui-ping Lu, Mieke Dewerchin, Peter Carmeliet, Ming-wei Wang, De-hua Yang
Summary: The growth of solid tumors relies on tumor vascularization and endothelial cells. Targeting the glycolytic activity of endothelial cells can normalize tumor vessels, reduce metastasis, and improve chemotherapy outcomes.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Cardiac & Cardiovascular Systems
Laura P. M. H. de Rooij, Lisa M. Becker, Laure Anne Teuwen, Bram Boeckx, Sander Jansen, Simon Feys, Stijn Verleden, Laurens Liesenborghs, Anna K. Stalder, Sasha Libbrecht, Tina Van Buyten, Gino Philips, Abhishek Subramanian, Sebastien J. Dumas, Elda Meta, Mila Borri, Liliana Sokol, Amelie Dendooven, Anh Co K. Truong, Jan Gunst, Pierre Van Mol, Jasmin D. Haslbauer, Katerina Rohlenova, Thomas Menter, Robbert Boudewijns, Vincent Geldhof, Stefan Vinckier, Jacob Amersfoort, Wim Wuyts, Dirk Van Raemdonck, Werner Jacobs, Laurens J. Ceulemans, Birgit Weynand, Bernard Thienpont, Martin Lammens, Mark Kuehnel, Guy Eelen, Mieke Dewerchin, Luc Schoonjans, Danny Jonigk, Jo van Dorpe, Alexandar Tzankov, Els Wauters, Massimiliano Mazzone, Johan Neyts, Joost Wauters, Diether Lambrechts, Peter Carmeliet
Summary: This study provides new insights into the abundance, expression patterns, and interactomes of endothelial cell (EC) subtypes in COVID-19 and idiopathic pulmonary fibrosis (IPF). The findings suggest the importance of ECs in the pathophysiology of both conditions and may contribute to future investigations into the progression and treatment of COVID-19 and IPF.
CARDIOVASCULAR RESEARCH
(2023)
Article
Critical Care Medicine
Eilise M. Ryan, Pranvera Sadiku, Patricia Coelho, Emily R. Watts, Ailiang Zhang, Andrew J. M. Howden, Manuel A. Sanchez-Garcia, Martin Bewley, Joby Cole, Brian J. McHugh, Wesley Vermaelen, Bart Ghesquiere, Peter Carmeliet, Giovanny Rodriguez Blanco, Alex Von Kriegsheim, Yolanda Sanchez, William Rumsey, James F. Callahan, George Cooper, Nicholas Parkinson, Kenneth Baillie, Doreen A. Cantrell, John McCafferty, Gourab Choudhury, Dave Singh, David H. Dockrell, Moira K. B. Whyte, Sarah R. Walmsley
Summary: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and impaired macrophage function. This study found that COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs) exhibit metabolic deficiencies and impairments in redox balance. Activation of the NRF2 pathway can rescue these defects and improve macrophage function in COPD.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Oncology
Monica Fernandez-Cortes, Daniel Delgado-Bellido, Eloisa Bermudez-Jimenez, Jesus M. Paramio, Francisco O'Valle, Stefan Vinckier, Peter Carmeliet, Angel Garcia-Diaz, F. Javier Oliver
Summary: Vasculogenic mimicry (VM) refers to the ability of aggressive tumor cells to develop pseudovascular structures without endothelial cells. This study investigated the role of hypoxia and PARP inhibition in VM. Results showed that the PARP inhibitor olaparib improved pericyte coverage and reduced metastasis in uveal melanoma xenografts with VM. PARP inhibition and hypoxia induced changes in melanoma tube formation and gene expression related to vasculogenesis, enhancing the endothelial-like phenotype of VM+ melanoma cells. Overall, PARP inhibitors have the potential to modulate VM characteristics and reduce metastatic spread in melanoma.
JOURNAL OF PATHOLOGY
(2023)
Review
Neurosciences
Thomas Waelchli, Jeroen Bisschop, Peter Carmeliet, Gelareh Zadeh, Philippe P. Monnier, Katrien De Bock, Ivan Radovanovic
Summary: This review examines the mechanisms of angiogenesis in brain development, brain vascular malformations, and brain tumors. The CNS critically relies on the formation and proper function of its vasculature during different stages, and angiogenesis plays a key role in vascular-dependent brain diseases. However, the exact molecular pathways and mechanisms underlying angiogenesis in the CNS are not fully understood.
NATURE REVIEWS NEUROSCIENCE
(2023)
Correction
Neurosciences
Carmen Ruiz de Almodovar, Pierre J. Fabre, Ellen Knevels, Cathy Coulon, Inmaculada Segura, Patrick C. G. Haddick, Liesbeth Aerts, Nicolas Delattin, Geraldine Strasser, Won-Jong Oh, Christian Lange, Stefan Vinckier, Jody Haigh, Coralie Fouquet, Chengua Gu, Kari Alitalo, Valerie Castellani, Marc Tessier-Lavigne, Alain Chedotal, Frederic Charron, Peter Carmeliet
Article
Multidisciplinary Sciences
Stefania Crotta, Matteo Villa, Jack Major, Katja Finsterbusch, Miriam Llorian, Peter Carmeliet, Joerg Buescher, Andreas Wack
Summary: Airway epithelial repair requires a shift from glycolysis to fatty acid oxidation. Promoting fatty acid oxidation enhances epithelial differentiation, offering potential therapeutic options. Defects in mucociliary clearance or barrier integrity lead to recurrent infections and chronic inflammation in the airway epithelium.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Liliana Sokol, Anne Cuypers, Anh-Co K. Truong, Ann Bouche, Katleen Brepoels, Joris Souffreau, Katerina Rohlenova, Stefan Vinckier, Luc Schoonjans, Guy Eelen, Mieke Dewerchin, Laura P. M. H. de Rooij, Peter Carmeliet
Summary: Translation of academic results into clinical practice is a significant challenge. In this study, the authors addressed this challenge by prioritizing and validating potential target genes from single-cell RNA-sequencing data. They focused on tip endothelial cell markers and identified four candidates that showed tip EC characteristics. This study highlights the importance of targeted assessment and prioritization of candidate genes for successful translation into clinical practice.
COMMUNICATIONS BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Brenda Morant-Ferrando, Daniel Jimenez-Blasco, Paula Alonso-Batan, Jesus Agulla, Rebeca Lapresa, Dario Garcia-Rodriguez, Sara Yunta-Sanchez, Irene Lopez-Fabuel, Emilio Fernandez, Peter Carmeliet, Angeles Almeida, Marina Garcia-Macia, Juan P. P. Bolanos
Summary: Astrocytes, a type of glial cells in the brain, primarily rely on glycolysis for energy production, indicating glucose as their main metabolic precursor. However, recent studies have shown that astrocytes also have the ability to metabolize fatty acids, and this metabolic pathway may play a role in preserving mitochondrial function and cognitive performance.
Meeting Abstract
Endocrinology & Metabolism
Shauni Loopmans, Steve Stegen, Katerina Rohlenova, Ingrid Stockmans, Karen Moermans, Peter Carmeliet, Geert Carmeliet
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Chunsik Lee, Rongyuan Chen, Guangli Sun, Xialin Liu, Xianchai Lin, Chang He, Liying Xing, Lixian Liu, Lasse D. Jensen, Anil Kumar, Harald F. Langer, Xiangrong Ren, Jianing Zhang, Lijuan Huang, Xiangke Yin, JongKyong Kim, Juanhua Zhu, Guanqun Huang, Jiani Li, Weiwei Lu, Wei Chen, Juanxi Liu, Jiaxin Hu, Qihang Sun, Weisi Lu, Lekun Fang, Shasha Wang, Haiqing Kuang, Yihan Zhang, Geng Tian, Jia Mi, Bi-Ang Kang, Masashi Narazaki, Aaron Prodeus, Luc Schoonjans, David M. Ornitz, Jean Gariepy, Guy Eelen, Mieke Dewerchin, Yunlong Yang, Jing-Song Ou, Antonio Mora, Jin Yao, Chen Zhao, Yizhi Liu, Peter Carmeliet, Yihai Cao, Xuri Li
Summary: Although the angiogenic effect of VEGF-B is not well understood, inhibitors of VEGF-B are being used in the treatment of neovascular diseases. In this study, we reveal a previously unrecognized function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway. We found that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Oncology
Qun Zeng, Mira Mousa, Aisha Shigna Nadukkandy, Lies Franssens, Halima Alnaqbi, Fatima Yousif Alshamsi, Habiba Al Safar, Peter Carmeliet
Summary: In this review, the authors summarize recent single-cell omics studies that have revealed the heterogeneity of human tumor endothelial cells and go on to demonstrate that these cells have phenotypes beyond simply being angiogenic. This finding has potential implications for improving the success rate of current anti-angiogenic therapies.
NATURE REVIEWS CANCER
(2023)
Article
Multidisciplinary Sciences
Anh-Co K. Truong, Lisa M. Becker, Nora Dekoning, Ann Bouche, Koen Veys, Baharak Hosseinkhani, Mieke Dewerchin, Guy Eelen, Peter Carmeliet
Summary: This paper provides a step-by-step description of the corneal thermal cauterization assay in mice and discusses ethical considerations and aspects related to animal welfare guidelines. The assay is a simple, low-cost, reproducible, insightful, and labor-saving method to evaluate the role of inflammation in angiogenesis and lymphangiogenesis.
Meeting Abstract
Cardiac & Cardiovascular Systems
R. Tillie, J. De Bruijn, R. Dobie, J. Perales-Paton, K. Van Kuijk, M. Gijbels, L. Temmerman, Y. Ghosheh, G. Goossens, P. Carmeliet, K. Ley, N. Henderson, J. Saez-Rodriguez, K. Wouters, J. Sluimer