Review
Peripheral Vascular Disease
Daniyal J. Jafree, David A. Long, Peter J. Scambler, Christiana Ruhrberg
Summary: Lymphatic vessels play critical roles in both health and disease, and research in this field is rapidly evolving. Recent studies have revealed new cellular mechanisms and diverse cell lineages involved in the formation of organ lymphatic vasculature.
Review
Biology
Koji Ando, Tomohiro Ishii, Shigetomo Fukuhara
Summary: Recruitment of mural cells to the vascular wall is essential for vasculature formation and function maintenance. Recent advances in zebrafish genetic tools have provided new possibilities for mural cell biology research, allowing for high-resolution study of mural cell development processes. Analysis of platelet-derived growth factor beta mutant zebrafish revealed well-conserved organotypic mural cell development in vertebrates with unique features of zebrafish.
Article
Medicine, Research & Experimental
Rene Haegerling, Malou Van Zanten, Rose Yinghan Behncke, Sascha Ulferts, Nils R. Hansmeier, Bruno Maerkl, Christian Witzel, Bernard Ho, Vaughan Keeley, Katie Riches, Sahar Mansour, Kristiana Gordon, Pia Ostergaard, Peter S. Mortimer
Summary: Superficial erythematous cutaneous vascular malformations may have a lymphatic origin rather than a blood vascular origin. Biopsy is necessary for accurate diagnosis. Port-wine birthmarks are cystic lesions that may indicate lymphatic malformation, while erythematous telangiectasias are expanded but nonmalformed lymphatic structures. The presence of erythrocytes accessing lymphatics through lympho-venous shunts explains the red color.
Review
Developmental Biology
Arndt F. Siekmann
Summary: This review discusses the functions of vascular mural cells in blood vessel formation and diameter regulation, as well as their interactions with endothelial cells. It also introduces the signaling pathways controlling mural cell development and highlights distinguishing features of mural cells located on different types of blood vessels. Therapeutic strategies involving mural cells to improve tissue ischemia and vascular efficiency in various diseases are explored.
Review
Pharmacology & Pharmacy
Alejandra Gonzalez-Loyola, Tatiana V. Petrova
Summary: The lymphatic vasculature plays a crucial role in maintaining body fluid balance, immune surveillance, and dietary fat absorption. Recent studies have shed light on the mechanisms of lymphatic vascular development and function.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Developmental Biology
Koji Ando, Yu-Huan Shih, Lwaki Ebarasi, Ann Grosse, Daneal Portman, Ayano Chiba, Kenny Mattonet, Claudia Gerri, Didier Y. R. Stainier, Naoki Mochizuki, Shigetomo Fukuhara, Christer Betsholtz, Nathan D. Lawson
Summary: The study demonstrates that Pdgfrb signaling plays a critical role in mural cells in zebrafish, and its absence can lead to issues such as cranial hemorrhage and vessel dilation. Similar to mice, pdgfrb mutant zebrafish also show defects in the structure of glomerulus, but normal development of hepatic stellate cells.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Di Peng, Koji Ando, Melina Hussmann, Marleen Gloger, Renae Skoczylas, Naoki Mochizuki, Christer Betsholtz, Shigetomo Fukuhara, Stefan Schulte-Merker, Nathan D. Lawson, Katarzyna Koltowska
Summary: In zebrafish, arterial mural cells have been identified as a crucial source of signals that guide the migration and survival of lymphatic endothelial cells (LECs), promoting the establishment of the lymphatic vascular network. The cooperative function of chemokine and growth factor signaling, particularly through the VEGFC-VEGFR3 pathway, plays a key role in LEC migration.
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.
Article
Biochemistry & Molecular Biology
Alexander Guenter, Vithiyanjali Sothilingam, Michael M. Orlich, Alfred Nordheim, Mathias W. Seeliger, Regine Muehlfriedel
Summary: This study further investigated the effects of MC SRF deficiency on the vasculature and function of the mature retina. Mutant retinal blood vessels exhibited various morphological and functional alterations, including vascular bulging, arteriovenous anastomoses formation, and retinal detachment. These changes resulted in irregular retinal blood pressure and flow distribution, leading to hypoxia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lin Grimm, Elizabeth Mason, Hujun Yu, Stefanie Dudczig, Virginia Panara, Tyrone Chen, Neil Bower, Scott Paterson, Maria Rondon Galeano, Sakurako Kobayashi, Anne Senabouth, Anne K. Lagendijk, Joseph Powell, Kelly A. Smith, Kazuhide S. Okuda, Katarzyna Koltowska, Benjamin M. Hogan
Summary: During lymphangiogenesis, the formation of lymphatic vasculature from blood vessels involves transdifferentiation of embryonic venous endothelial cells into lymphatic endothelial cells. This study provides a comprehensive single-cell atlas of lymphangiogenesis in zebrafish, identifying new markers and characteristics of lymphatic endothelial cell differentiation and uncovering the downstream targets and regulatory regions controlled by Prox1. The findings shed light on the role of Prox1 in lymphatic endothelial cell fate specification and differentiation.
Review
Biochemistry & Molecular Biology
Sudarshan Bhattacharjee, Yang Lee, Bo Zhu, Hao Wu, Yabing Chen, Hong Chen
Summary: Epsins 1 and 2, as adaptor proteins, play essential roles in regulating cell signaling pathways in angiogenesis and lymphangiogenesis by interacting with lipids and proteins. Understanding the molecular mechanisms of epsin-mediated regulation may have therapeutic implications for diseases like atherosclerosis and diabetes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Aurore Dumond, Christopher Montemagno, Valerie Vial, Renaud Grepin, Gilles Pages
Summary: The study developed specific mouse monoclonal antibodies targeting VEGFC for the treatment of mccRCC, showing potential in inhibiting the growth of metastatic clear cell renal cell carcinoma.
Article
Developmental Biology
Elvin Leonard, Ricardo J. Figueroa, Jeroen Bussmann, Nathan D. Lawson, Julio D. Amigo, Arndt F. Siekmann
Summary: The study reveals the important role of Pdgfrb signaling in mural cell recruitment and arterial development. Mural cells have different expression characteristics and origins in different locations. Moreover, newly formed mural cells during tissue regeneration do not derive from pre-existing cells.
Article
Biochemistry & Molecular Biology
Giovanna Azzarito, Michele Visentin, Brigitte Leeners, Raghvendra K. Dubey
Summary: Vascular and lymphatic vessels play a crucial role in breast cancer growth and metastasis. The study found that the secretome of estrogen receptor-positive breast cancer cells can stimulate vascular angiogenesis and inhibit lymphatic growth, which has significant pathological and physiological implications for breast cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Michael O'Hare, Joseph F. Arboleda-Velasquez
Summary: The Notch signaling pathway plays a crucial role in cell fate determination, particularly in vascular development. Aberrant Notch signaling can lead to severe vascular abnormalities. The interaction between endothelial cells and mural cells is essential for maintaining vascular network stability.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2022)
Article
Oncology
Tove Bekkhus, Teemu Martikainen, Anna Olofsson, Mathias Franzen Boger, Daniel Vasiliu Bacovia, Fredrik Warnberg, Maria H. Ulvmar
Summary: Invasive breast cancer leads to dramatic changes in tumor-draining lymph nodes, affecting the recruitment of T-lymphocytes and disrupting essential functions within the immune system. These changes may serve as potential biomarkers for predicting disease progression in human cancer.
Article
Biochemistry & Molecular Biology
Magda N. Hernandez Vasquez, Maria H. Ulvmar, Alejandra Gonzalez-Loyola, Ioannis Kritikos, Ying Sun, Liqun He, Cornelia Halin, Tatiana Petrova, Taija Makinen
Summary: This study identifies FOXP2 as a new flow-induced transcriptional regulator of collecting lymphatic vessel morphogenesis. Loss of FOXP2 results in enlarged collecting vessels and defective valves, highlighting the unique transcription factor codes in establishing vessel-type-specific endothelial cell identities.
Article
Immunology
Jorge Arasa, Victor Collado-Diaz, Ioannis Kritikos, Jessica Danielly Medina-Sanchez, Mona Carina Friess, Elena Caroline Sigmund, Philipp Schineis, Morgan Campbell Hunter, Carlotta Tacconi, Neil Paterson, Takashi Nagasawa, Friedemann Kiefer, Taija Makinen, Michael Detmar, Markus Moser, Tim Laemmermann, Cornelia Halin
Summary: DC migration to dLNs is a slow process involving DCs entering lymphatic capillaries, crawling into lymphatic collectors, and rapidly transported to dLNs. Inflammation induces BM degradation and upregulation of VCAM-1 in collectors, facilitating DC entry into collectors in a CCR7- and beta 1 integrin-dependent manner. Loss of beta 1-integrins in DCs or VCAM-1 in collectors has the greatest impact on DC migration to dLNs at early time points.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Developmental Biology
Henrik Ortsater, Magda N. Hernandez-Vasquez, Maria H. Ulvmar, Alexander Gow, Taija Makinen
Summary: The generation of a transgenic mouse expressing tamoxifen inducible CreER(T2) under the control of Cldn11 promoter allows for selective and temporally controlled targeting of lymphatic valve endothelial cells. The study shows that CLDN11 is specifically expressed in lymphatic valves and not required for their development, with efficient labeling of valve endothelial cells observed. This mouse model provides a valuable tool for functional studies of valves.
Article
Medicine, Research & Experimental
Di Chen, Elizabeth D. Hughes, Thomas L. Saunders, Jiangping Wu, Magda N. Hernandez Vasquez, Taija Makinen, Philip D. King
Summary: This study demonstrates that RASA1 and EPHB4 function in the same signaling pathway to protect against the development of CM-AVM, independent of physical interaction. These findings have important implications for possible treatment of this disease.
Article
Hematology
Simon Stritt, Paquita Nurden, Alan T. Nurden, Jean-Francois Schved, Jean-Claude Bordet, Maguelonne Roux, Marie-Christine Alessi, David-Alexandre Tregouet, Taija Makinen, Muriel Giansily-Blaizot
Summary: Vascular homeostasis is disrupted in various diseases, and the Apold1 gene plays a crucial role in regulating endothelial function. Silencing Apold1 in endothelial cells leads to changes in cell junction-cytoskeletal interface and endothelial permeability, along with the release of Weibel-Palade bodies (WPB) contents. The absence of Apold1 also impairs the autophagy flux and is associated with an inherited bleeding disorder. The findings highlight the importance of Apold1 in maintaining vascular homeostasis and suggest the need for testing endothelial cell function in patients with bleeding disorders.
Editorial Material
Pharmacology & Pharmacy
Ines Martinez-Corral, Natalie L. Trevaskis, Melissa Garcia-Caballero
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell & Tissue Engineering
Lars Muhl, Liqun He, Ying Sun, Maarja Andaloussi Mae, Riikka Pietila, Jianping Liu, Guillem Genove, Lei Zhang, Yuan Xie, Stefanos Leptidis, Giuseppe Mocci, Simon Stritt, Ahmed Osman, Andrey Anisimov, Karthik Amudhala Hemanthakumar, Markus Rasanen, Emil M. Hansson, Johan Bjorkegren, Michael Vanlandewijck, Klas Blomgren, Taija Makinen, Xiao-Rong Peng, Yizhou Hu, Patrik Ernfors, Thomas D. Arnold, Kari Alitalo, Urban Lendahl, Christer Betsholtz
Summary: ACE2 receptor is strongly expressed in pericytes in the CNS, heart, and pancreas, as well as in perineurial and adrenal fibroblasts, but not in endothelial cells. In the lung, ACE2 is expressed in bronchial epithelium and alveolar type II cells. The expression of ACE2 is organ-specific, with bronchial epithelium expressing it at birth, brain pericytes expressing it before birth, and heart pericytes expressing it after postnatal day 10.5. Understanding the vascular localization of ACE2 expression is crucial for interpreting data from mouse models of COVID-19 and may provide insights into the cause of vascular COVID-19 complications.
Article
Oncology
Tove Bekkhus, Christophe Avenel, Sabella Hanna, Mathias Franzen Boger, Anna Klemm, Daniel Vasiliu Bacovia, Fredrik Warnberg, Carolina Wahlby, Maria H. Ulvmar
Summary: Vascular remodeling is common in human cancer and has potential as future biomarkers for disease progression and tumor immunity status. A fully automated tool named HEV-finder can detect and classify high endothelial venule (HEV) dilation in tumor-draining lymph nodes, laying the groundwork for exploration of HEV dilation as a biomarker.
JOURNAL OF PATHOLOGY
(2022)
Article
Immunology
Milena Petkova, Marle Kraft, Simon Stritt, Ines Martinez-Corral, Henrik Ortsaeter, Michael Vanlandewijck, Bojana Jakic, Eulalia Baselga, Sandra D. Castillo, Mariona Graupera, Christer Betsholtz, Taija Maekinen
Summary: Researchers have identified a new subtype of lymphatic endothelial cells called iLECs, which are positive for Ptx3 and are involved in PI3K-driven lymphatic malformations. These cells recruit pro-lymphangiogenic macrophages and promote pathological lymphatic vessel growth. Understanding the specific disease pathogenesis of different vessel types could lead to the development of more efficient therapies.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Tove Bekkhus, Anna Olofsson, Ying Sun, Peetra U. Magnusson, Maria H. Ulvmar
Summary: LN lipomatosis is a common phenomenon associated with aging, characterized by the gradual replacement of LN parenchyma with adipose tissue. The mechanisms behind these changes and their effects on LN are still unknown. However, our study suggests that the initiation of lipomatosis is associated with transdifferentiation of LN fibroblasts into adipocytes.
JOURNAL OF PATHOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Silvia Arroz-Madeira, Tove Bekkhus, Maria H. Ulvmar, Tatiana V. Petrova
Summary: Secondary lymphoid organs, such as lymph nodes, have specialized niches that optimize the encounter of naive lymphocytes with antigens and antigen-presenting cells, leading to optimal adaptive immune responses. Lymphatic vessels of lymphoid organs are specialized to perform various tasks, including antigen presentation, immune cell trafficking, activation modulation, and survival factor provision. Recent studies have provided insights into the molecular basis of this specialization, opening avenues for understanding immune-vascular interactions and their applications.
CIRCULATION RESEARCH
(2023)
Article
Medicine, Research & Experimental
Emilia A. Korhonen, Aino Murtomaki, Sawan Kumar Jha, Andrey Anisimov, Anne Pink, Yan Zhang, Simon Stritt, Inam Liaqat, Lukas Stanczuk, Laura Alderfer, Zhiliang Sun, Emmi Kapiainen, Abhishek Singh, Ibrahim Sultan, Anni Lantta, Veli-Matti Leppanen, Lauri Eklund, Yulong He, Hellmut G. Augustin, Kari Vaahtomeri, Pipsa Saharinen, Taija Makinen, Kari Alitalo
Summary: This study reveals the involvement of Ang2 in VEGF-C-induced lymphangiogenesis through the PI3K/Akt signaling pathway in lymphatic endothelial cells. Blockade of Ang2 or deletion of Tie receptors in LECs inhibits lymphangiogenesis. The study highlights the important crosstalk between VEGF-C and Ang signaling pathways and suggests potential therapeutic approaches targeting Ang2/Tie/PI3K signaling for lymphangiogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Letter
Medicine, General & Internal
Christer Betsholtz, Konstantin Gaengel, Taija Makinen
NEW ENGLAND JOURNAL OF MEDICINE
(2022)