Review
Behavioral Sciences
Deborah Chiabrando, Veronica Fiorito, Sara Petrillo, Francesca Bertino, Emanuela Tolosano
Summary: This study examines the relationship between heme and the pathophysiology of pain, highlighting the important regulatory role of heme in nociception and its association with pain-related diseases. However, the molecular mechanisms linking heme to pain pathways remain unclear at present.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Cell Biology
Veronica Fiorito, Anna Lucia Allocco, Sara Petrillo, Elena Gazzano, Simone Torretta, Saverio Marchi, Francesca Destefanis, Consiglia Pacelli, Valentina Audrito, Paolo Provero, Enzo Medico, Deborah Chiabrando, Paolo Ettore Porporato, Carlotta Cancelliere, Alberto Bardelli, Livio Trusolino, Nazzareno Capitanio, Silvia Deaglio, Fiorella Altruda, Paolo Pinton, Simone Cardaci, Chiara Riganti, Emanuela Tolosano
Summary: There is a functional axis between heme synthesis and heme export, with heme efflux through the plasma membrane sustaining heme synthesis and modulating tricarboxylic acid cycle and oxidative phosphorylation. Inhibition of heme export reduces heme synthesis and promotes TCA cycle fueling and flux as well as oxidative phosphorylation. These findings suggest that the heme synthesis-export system modulates TCA cycle and oxidative metabolism, providing a mechanistic basis for their enhancement in cells with high-energy demand.
Editorial Material
Biochemistry & Molecular Biology
Veronica Fiorito, Emanuela Tolosano
Summary: Hemopexin, a plasma protein with high affinity for heme, has been overlooked in cancer despite its significant role in various heme-related disorders. This review aims to provide an update on the involvement of hemopexin in cancer and stimulate further research on this topic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Chiara Camillo, Nicola Facchinello, Giulia Villari, Giulia Mana, Noemi Gioelli, Chiara Sandri, Matteo Astone, Dora Tortarolo, Fabiana Clapero, Dafne Gays, Roxana E. Oberkersch, Marco Arese, Luca Tamagnone, Donatella Valdembri, Massimo M. Santoro, Guido Serini
Summary: Dynamic modulation of endothelial cell adhesion and barrier function by the adhesion G protein-coupled receptor Latrophilin 2 (LPHN2) and its ligand FLRT2 plays a crucial role in blood vessel development and functioning.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liaisan Arslanbaeva, Giovanni Tosi, Marco Ravazzolo, Manuela Simonato, Francesco A. Tucci, Salvatore Pece, Paola Cogo, Massimo M. Santoro
Summary: This study demonstrates that the expression of UBIAD1 is associated with poor overall survival in human melanoma patients, and UBIAD1 and CoQ10 levels are upregulated in melanoma cells. The study also shows that UBIAD1 and plasma membrane CoQ10 sustain melanoma cell survival and proliferation by preventing lipid peroxidation and cell death.
Article
Oncology
Anna Lucia Allocco, Francesca Bertino, Sara Petrillo, Deborah Chiabrando, Chiara Riganti, Alberto Bardelli, Fiorella Altruda, Veronica Fiorito, Emanuela Tolosano
Summary: This study demonstrates that interfering with heme metabolism can increase the sensitivity of tumor cells to overcome drug resistance and inhibit tumor growth. The existence of this concept further strengthens the idea of targeting heme metabolism to counteract tumor progression.
Review
Oncology
Jacopo Lidonnici, Massimo M. Santoro, Roxana E. Oberkersch
Summary: Angiogenesis plays an important role in tumor growth and metastasis, and understanding the metabolic characteristics and interactions of tumor endothelial cells (TECs) with tumor cells is crucial. The metabolic differences between normal and tumor vasculature provide a basis for developing targeted therapies with higher specificity and fewer side effects, improving patient outcomes.
Article
Peripheral Vascular Disease
Sara Petrillo, F. De Giorgio, F. Bertino, F. Garello, V Bitonto, D. L. Longo, S. Mercurio, G. Ammirata, A. L. Allocco, V Fiorito, D. Chiabrando, F. Altruda, E. Terreno, P. Provero, L. Munaron, T. Genova, A. Novoa, A. R. Carlos, S. Cardoso, M. Mallo, M. P. Soares, E. Tolosano
Summary: The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is highly expressed in angiogenic endothelial cells (ECs) and has a critical role in developmental and pathological angiogenesis. Deficiency of FLVCR1a leads to abnormal vascular networks in multiple models, including defective vessel formation in zebrafish embryos, reduced retinal vasculature expansion and EC proliferation in mice, and disorganized and dysfunctional tumor blood vessels. These findings suggest FLVCR1a as a potential therapeutic target for diseases characterized by aberrant neovascularization.
Article
Hematology
Enrica Federti, Francesca Vinchi, Iana Iatcenko, Alessandra Ghigo, Alessandro Matte, Serge Cedrick Mbiandjeu Toya, Angela Siciliano, Deborah Chiabrando, Emanuela Tolosano, Steven Zebulon Vance, Veronica Riccardi, Immacolata Andolfo, Manuela Iezzi, Alessia Lamolinara, Achille Iolascon, Lucia De Franceschi
Summary: Cardiomyopathy greatly affects the well-being and survival of patients with 13-thalassemia or transfusion-dependent myelodysplastic syndromes. Recent research has found a connection between Nrf2 activity and iron metabolism. In this study, Nrf2-/- mice developed age-dependent cardiomyopathy characterized by oxidation, degradation of SERCA2A, and iron accumulation. The absence of Nrf2 paradoxically protected against heart iron accumulation when exposed to an iron overload diet. The activation of the unfolded protein response system and cardiac fibrosis were observed in a model of 13-thalassemia independent of heart iron content. These findings provide insights into potential early treatment for cardiomyopathy in patients with 13-thalassemia.
Article
Cell Biology
Gabriele Saccu, Valeria Menchise, Chiara Gai, Marina Bertolin, Stefano Ferrari, Cristina Giordano, Marta Manco, Walter Dastru, Emanuela Tolosano, Benedetta Bussolati, Enzo Calautti, Giovanni Camussi, Fiorella Altruda, Sharmila Fagoonee
Summary: A study found that topical application of bone-marrow-derived mesenchymal stromal/stem cell-derived extracellular vesicles (BMSC-EVs) can accelerate corneal damage repair, suggesting a promising cell-free approach for treating burns in the avascularized region of the eye.
Article
Cardiac & Cardiovascular Systems
Matteo Astone, Roxana E. Oberkersch, Giovanni Tosi, Alberto Biscontin, Massimo M. Santoro
Summary: This study demonstrates that endothelial cells possess an endogenous circadian clock, and core clock genes exhibit robust circadian oscillations. Impairing the function of the circadian clock transcriptional activator BMAL1 leads to angiogenesis defects in both developmental and pathological contexts. BMAL1 regulates endothelial cell cycle progression by binding to the promoters of CCNA1 and CDK1 genes.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemical Research Methods
Cristina Arce Recatala, Mattia Albiero, Massimo Mattia Santoro
Summary: This article presents a protocol for evaluating post-natal angiogenesis in a mouse hind limb ischemia model, which is a useful tool for assessing metabolic and cellular responses. The protocol involves inducing a severe restriction of blood supply to mimic the real-life scenario observed in clinical settings, followed by laser Doppler imaging to compare the post-ischemic responses of different mouse strains in triggering compensatory arteriogenesis.
Article
Endocrinology & Metabolism
Nicola Facchinello, Matteo Astone, Matteo Audano, Roxana E. Oberkersch, Marianna Spizzotin, Enrica Calura, Madalena Marques, Mihaela Crisan, Nico Mitro, Massimo M. Santoro
Summary: Endothelial cell metabolism regulates blood vessel maturation by controlling vascular matrix composition and the recruitment of vascular mural cells.