Article
Endocrinology & Metabolism
Nele Warmke, Fiona Platt, Alexander F. Bruns, Claire H. Ozber, Natalie J. Haywood, Yilizila Abudushalamu, Charles Slater, Victoria Palin, Piruthivi Sukumar, Stephen B. Wheatcroft, Nadira Y. Yuldasheva, Mark T. Kearney, Kathryn J. Griffin, Richard M. Cubbon
Summary: In this study, pericyte insulin signaling was found to promote angiopoietin-1 secretion and endothelial Tie2 signaling. Disruption of this pathway led to excessive vascular sprouting and venous plexus abnormalities, mimicking diabetic retinopathy characteristics. Future research should focus on evaluating the role of pericyte insulin signaling in this disease.
Article
Endocrinology & Metabolism
Nele Warmke, Fiona Platt, Alexander F. Bruns, Claire H. Ozber, Natalie J. Haywood, Yilizila Abudushalamu, Charles Slater, Victoria Palin, Piruthivi Sukumar, Stephen B. Wheatcroft, Nadira Y. Yuldasheva, Mark T. Kearney, Kathryn J. Griffin, Richard M. Cubbon
Summary: Pericytes play a crucial role in regulating vascular development and stability, with dysfunction potentially contributing to diabetic retinopathy. Knockout of insulin receptors in pericytes resulted in abnormal vascular development, indicating the importance of insulin signaling in promoting angiopoietin-1 secretion and endothelial Tie2 signaling.
Review
Chemistry, Multidisciplinary
Chao Ye, Fen Zheng, Nan Wu, Guo-qing Zhu, Xiu-zhen Li
Summary: Vascular remodeling plays a crucial role in the development of various vascular diseases and is closely associated with the release of extracellular vesicles (EVs). EVs impact vascular remodeling by affecting oxidative stress, inflammation, calcification, and lipid plaque formation. Therefore, EVs have the potential to be used as biomarkers for diagnosis and prognosis, as well as therapeutic targets for vascular remodeling and cardiovascular diseases.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Yaqian Huang, Zongmin Li, Lulu Zhang, Huan Tang, Heng Zhang, Chu Wang, Selena Ying Chen, Dingfang Bu, Zaifeng Zhang, Zhigang Zhu, Piaoliu Yuan, Kun Li, Xiaoqi Yu, Wei Kong, Chaoshu Tang, Youngeun Jung, Renan B. Ferreira, Kate S. Carroll, Junbao Du, Jing Yang, Hongfang Jin
Summary: Recent researches have found that sulfur dioxide(SO2) may mediate the transformation of hydrogen peroxide(H2O2) into peroxymonosulfite, leading to the sulfenylation of protein cysteine residues. This sulfenylation has a dynamic impact on vascular smooth muscle cells, particularly affecting the transcriptional modulator Smad3 and its function in vascular remodeling and hypertension.
Article
Hematology
Jing Du, Benjamin R. Thomson, Tuncer Onay, Susan E. Quaggin
Summary: Studies have shown that Tie1 plays a crucial role in the development and function of Schlemm's canal. Loss of Tie1 leads to hypomorphic Schlemm's canal and elevated intraocular pressure. Therefore, Tie1 may be a novel target for future glaucoma therapies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sariya Meephat, Patoomporn Prasatthong, Prapassorn Potue, Sarawoot Bunbupha, Poungrat Pakdeechote, Putcharawipa Maneesai
Summary: Diosmetin demonstrated a reduction in blood pressure and alleviation of vascular abnormalities in experimentally hypertensive rats by exerting antioxidant and anti-inflammatory effects, and modulating the expression of Nrf2/HO1 and p-JNK/NF-kappa B proteins.
Article
Cardiac & Cardiovascular Systems
Alberto Canfran-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andres-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernandez-Fuertes, Joseph W. Fowler, Diego Gomez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernandez-Hernando, Yajaira Suarez
Summary: The accumulation of 25-hydroxycholesterol (25-HC) in human coronary atherosclerotic lesions accelerates atherosclerosis progression and promotes plaque instability through autocrine and paracrine actions. Macrophage-derived 25-HC intensifies the inflammatory response of lipid-loaded macrophages and inhibits smooth muscle cell migration within the plaque. These effects are independent of 25-HC-mediated modulation of transcriptional activity.
Review
Biochemistry & Molecular Biology
Marta T. Gomes, Yang Bai, Simone R. Potje, Lu Zhang, Angelia D. Lockett, Roberto F. Machado
Summary: This review discusses the role of bioenergetic and inflammatory impairments in the development of pulmonary arterial hypertension (PAH).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Jugal Kishore Das, Fengguang Guo, Carrie Hunt, Shelby Steinmeyer, Julia A. Plocica, Koichi S. Kobayashi, Yufang Ding, Arul Jayaraman, Thomas A. Ficht, Robert C. Alaniz, Paul de Figueiredo, Jianxun Song
Summary: This study genetically engineered a bacterium to produce a tryptophan metabolite that controls the fate and function of T cells, resulting in enhanced T-reg cell function and reduced incidence of autoimmune arthritis and joint damage. Findings demonstrate the potential of metabolically engineered bacteria in improving immunotherapy efficacy and reducing inflammation.
Article
Cardiac & Cardiovascular Systems
Guanxin Zhang, Qing Qin, Chen Zhang, Xiaobo Sun, Kyosuke Kazama, Bing Yi, Fang Cheng, Zhi-Fu Guo, Jianxin Sun
Summary: The study finds that NDRG1 plays an essential role in cell differentiation, proliferation, and stress responses. The expression of NDRG1 significantly increases in cytokine-stimulated endothelial cells and atherosclerotic lesions. Inhibition of NDRG1 not only suppresses the expression of procoagulant molecules but also exerts antithrombotic effects in endothelial cells, highlighting its potential as a therapeutic target for vascular diseases.
CIRCULATION RESEARCH
(2023)
Review
Hematology
Prisca K. Lin, George E. Davis
Summary: Large and medium-sized vessels react differently from capillaries to stimuli inducing vascular disease, undergoing extracellular matrix (ECM) remodeling. While arteries persist and undergo modifications in response to injurious stimuli, capillaries may undergo regression responses.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Ninelia Minaskan Karabid, Tobias Wiedemann, Sebastian Gulde, Hermine Mohr, Renu Chandra Segaran, Julia Geppert, Maria Rohm, Giovanni Vitale, Germano Gaudenzi, Alessandra Dicitore, Donna Pauler Ankerst, Yiyao Chen, Rickmer Braren, Georg Kaissis, Franz Schilling, Mathias Schillmaier, Graeme Eisenhofer, Stephan Herzig, Federico Roncaroli, Juergen B. Honegger, Natalia S. Pellegata
Summary: Invasive nonfunctioning pituitary neuroendocrine tumors (PitNETs) are difficult to remove and current therapies often fail. This study investigated the ANGPT2/TIE2 axis in NF-PitNETs and found that PitNET cells express functional TIE2 receptors and secrete bioactive ANGPT2, which promotes tumor cell growth. Inhibition of this signaling pathway showed promise in inhibiting PitNET growth in various models. Therefore, the ANGPT2/TIE2 axis could be a potential therapeutic target for NF-PitNETs.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Emmi Kapiainen, Minna K. Kihlstrom, Riikka Pietila, Mika Kaakinen, Veli-Pekka Ronkainen, Hongmin Tu, Anne Heikkinen, Raman Devarajan, Ilkka Miinalainen, Anna Laitakari, Mohammadhassan Ansarizadeh, Qin Zhang, Gong-Hong Wei, Lloyd Ruddock, Taina Pihlajaniemi, Harri Elamaa, Lauri Eklund
Summary: The study investigates the role of different forms of ANGPT2 in cancer, revealing that ANGPT2(443) plays a crucial role in vascular remodeling, tumor growth, and metastasis.
Article
Multidisciplinary Sciences
Raquel Roldan-Montero, Juan M. Perez-Saez, Isabel Cerro-Pardo, Jorge Oller, Diego Martinez-Lopez, Estefania Nunez, Sebastian M. Maller, Carmen Gutierrez-Munoz, Nerea Mendez-Barbero, Joan C. Escola-Gil, Jean-Baptiste Michel, Maria Mittelbrunn, Jesus Vazquez, Luis M. Blanco-Colio, Gabriel A. Rabinovich, Jose L. Martin-Ventura
Summary: Galectin-1 (Gal-1) plays a significant role as a therapeutic target for atherosclerosis and abdominal aortic aneurysm (AAA). Lack of Gal-1 leads to severe atherosclerosis and VSMC phenotypic switch, while treatment with recombinant Gal-1 prevents these effects and alleviates the conditions of atherosclerosis and AAA.
Article
Pharmacology & Pharmacy
Liangqingqing Yin, Jie Bai, Wei-Jia Yu, Ying Liu, Hui-Hua Li, Qiu-Yue Lin
Summary: The adhesion of monocytes to the vascular endothelium is an important factor in inflammatory response and contributes to hypertension and vascular remodeling. The role of VCAM-1 in Ang II-induced hypertension and vascular dysfunction is not well understood. Blocking VCAM-1 with a neutralizing antibody can alleviate these effects and represents a novel therapeutic approach for hypertension.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Ngoc Anh Nguyen, Xiaobo Huang, Luz E. Cabrera, Pirkka T. Pekkarinen, Kirsten Nowlan, Tomas Strandin, Anu Kantele, Olli Vapalahti, Santtu Heinonen, Eliisa Kekalainen
Summary: This study evaluated and compared the performance of four commercial whole blood cryopreservation kits and found that PROT-1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets and the activated phenotypes of neutrophils. Cytodelics also allowed reliable detection of lymphopenia and granulocyte expansion in longitudinal clinical samples from acute COVID-19 patients.
Article
Biochemistry & Molecular Biology
Kathrin Barth, Verica Vasic, Brennan McDonald, Nora Heinig, Marc-Christoph Wagner, Ulrike Schumann, Cora Roehlecke, Frank Bicker, Lana Schumann, Konstantin Radyushkin, Jan Baumgart, Stefan Tenzer, Frauke Zipp, Matthias Meinhardt, Kari Alitalo, Irmgard Tegeder, Mirko H. H. Schmidt
Summary: Mature neurons, neural stem cells, and neural precursor cells secrete the neurovascular protein EGFL7 to shape the neurogenic niche of the hippocampus. Ablation of EGFL7 leads to increased neurogenesis and is correlated with elevated expression of VEGF-D. Infusion of VEGF-D increases neurogenesis, while its knockout decreases neurogenesis. Furthermore, EGFL7 knockout mice show improved spatial memory and memory consolidation in the hippocampus.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ivy K. N. Chiang, Matthew S. Graus, Nils Kirschnick, Tara Davidson, Winnie Luu, Richard Harwood, Keyi Jiang, Bitong Li, Yew Yan Wong, Mehdi Moustaqil, Emmanuelle Lesieur, Renae Skoczylas, Valerie Kouskoff, Jan Kazenwadel, Luis Arriola-Martinez, Emma Sierecki, Yann Gambin, Kari Alitalo, Friedmann Kiefer, Natasha L. Harvey, Mathias Francois
Summary: SOX7, a BEC-specific transcription factor, modulates the expression level of angiocrine signals in blood vascular endothelial cells (BECs) to pattern lymphatic vessels. It directly represses the transcription of Vegfc, a major lymphangiogenic growth factor, and interacts with HEY1 to regulate Notch pathway. Our finding reveals the importance of SOX7 in modulating downstream signaling events crucial for lymphatic patterning.
Article
Cardiac & Cardiovascular Systems
Anne-Maj Samuelsson, Theda Ulrike Patricia Bartolomaeus, Harithaa Anandakumar, Irene Thowsen, Elham Nikpey, Jianhua Han, Lajos Marko, Kenneth Finne, Olav Tenstad, Johannes Eckstein, Nikolaus Berndt, Titus Kuehne, Sarah Kedziora, Ibrahim Sultan, Trude Skogstrand, Tine Karlsen, Harri Nurmi, Sofia K. Forslund, Entela Bollano, Kari Alitalo, Dominik N. Muller, Helge Wiig
Summary: This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in heart failure, and finds that VEGF-B TG accelerates metabolic maladaptation, leading to structural cardiomyopathy and systolic heart failure.
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
Biochemistry & Molecular Biology
Katri Vaparanta, Anne Jokilammi, Ilkka Paatero, Johannes A. Merilahti, Juho Heliste, Karthik Amudhala Hemanthakumar, Riikka Kivela, Kari Alitalo, Pekka Taimen, Klaus Elenius
Summary: In this study, it is demonstrated that Neuregulin-1 (NRG-1) regulates myocardial growth through the STAT5b pathway. Disruption of the NRG-1/ERBB4 pathway or inhibition of Dynamin-2 reduces STAT5b activation and cardiomyocyte hypertrophy. Activation of Stat5 is also observed in NRG-1-induced myocardial growth in zebrafish embryos, and knockdown of stat5b leads to reduced myocardial growth and cardiac function. Furthermore, the NRG-1/ERBB4/STAT5b pathway is differentially regulated in patients with pathological cardiac hypertrophy.
Article
Infectious Diseases
Sohvi Kaariainen, Jukka Ollgren, Timothee Dub, Outi Laine, Marjatta Sinisalo, Jussi Hepojoki, Tomas Strandin, Eliisa Kekalainen, Jussi Sane, Outi Lyytikainen
Summary: This study found that there is an increased risk of lymphoid malignancies, specifically mature B cell neoplasms, during 3-<12 months and 1-<5 years after PUUV infection. This suggests an association between PUUV infection and lymphoid malignancies.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Shahid Rehan, Dale Tranter, Phillip P. P. Sharp, Gregory B. B. Craven, Eric Lowe, Janet L. L. Anderl, Tony Muchamuel, Vahid Abrishami, Suvi Kuivanen, Nicole A. A. Wenzell, Andy Jennings, Chakrapani Kalyanaraman, Tomas Strandin, Matti Javanainen, Olli Vapalahti, Matthew P. P. Jacobson, Dustin McMinn, Christopher J. J. Kirk, Juha T. Huiskonen, Jack Taunton, Ville O. O. Paavilainen
Summary: This study describes a cyclic depsipeptide called KZR-8445 that selectively disrupts the biogenesis of secretory and membrane proteins in a signal peptide-dependent manner by targeting the Sec61 translocon. KZR-8445 effectively inhibits the secretion of pro-inflammatory cytokines in immune cells and demonstrates therapeutic efficacy in a mouse model of rheumatoid arthritis. The binding of KZR-8445 stabilizes the lateral gate helices of Sec61, preventing the movement of select signal peptides into the lipid bilayer and providing a framework for the discovery of novel therapeutics that modulate Sec61-mediated protein biogenesis in a targeted manner.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Eva Mittler, Alexandra Serris, Emma S. Esterman, Catalina Florez, Laura C. Polanco, Cecilia M. O'Brien, Megan M. Slough, Janne Tynell, Remigius Groning, Yan Sun, Dafna M. Abelson, Anna Z. Wec, Denise Haslwanter, Markus Keller, Chunyan Ye, Russel R. Bakken, Rohit K. Jangra, John M. Dye, Clas Ahlm, C. Garrett Rappazzo, Rainer G. Ulrich, Larry Zeitlin, James C. Geoghegan, Steven B. Bradfute, Simone Sidoli, Mattias N. E. Forsell, Tomas Strandin, Felix A. Rey, Andrew S. Herber, Laura M. Walker, Kartik Chandran, Pablo Guardado-Calvo
Summary: We isolated a monoclonal broadly neutralizing antibody from a Puumala virus-experienced human donor and determined its structure when bound to the viral fusion complex. The antibody recognizes conserved sequences in the fusion loop of the Gc protein and the main chain of variable Gn sequences, thereby locking the Gn/Gc heterodimer in its prefusion conformation. We optimized the antibody variant to overcome its limited potency against the divergent Andes virus at endosomal acidic pH, making it a promising therapeutic candidate for pan-hantavirus treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Tobias L. Freitag, Riku Fagerlund, Nihay Laham Karam, Veli-Matti Leppanen, Hasan Ugurlu, Ravi Kant, Petri Makinen, Ahmed Tawfek, Sawan Kumar Jha, Tomas Strandin, Katarzyna Leskinen, Jussi Hepojoki, Tapio Kesti, Lauri Kareinen, Suvi Kuivanen, Emma Koivulehto, Aino Sormunen, Svetlana Laidinen, Ayman Khattab, Paivi Saavalainen, Seppo Meri, Anja Kipar, Tarja Sironen, Olli Vapalahti, Kari Alitalo, Seppo Yla-Herttuala, Kalle Saksela
Summary: Intranasal administration of adenoviral vector vaccines can induce mucosal immunity and protect mice from SARS-CoV-2 infection, supporting the potential of this approach for preventing transmission of the virus.
Article
Virology
Antti Vaheri, Teemu Smura, Hanna Vauhkonen, Jussi Hepojoki, Tarja Sironen, Tomas Strandin, Johanna Tietavainen, Tuula Outinen, Satu Maekelae, Ilkka Poersti, Jukka Mustonen
Summary: The clinical outcome of Puumala hantavirus (PUUV) infection varies widely, with some cases being asymptomatic and others leading to severe hemorrhagic fever with renal syndrome (HFRS) and even death. The severity of the infection may be influenced by genetic factors such as human leukocyte antigen (HLA) alleles and genes related to tumor necrosis factor (TNF) and complement system. Autoimmune phenomena, Epstein-Barr virus infection, and individual differences in ocular and central nervous system manifestations are also associated with PUUV infection.
Article
Immunology
Zhilin Li, Salli Antila, Harri Nurmi, Dmitri Chilov, Emilia A. Korhonen, Shentong Fang, Sinem Karaman, Britta Engelhardt, Kari Alitalo
Summary: The recent discovery of lymphatic vessels in the dura mater has potential implications for alternative therapeutics in CNS disorders. However, inhibiting the VEGF-C/VEGFR3 signaling pathway does not affect the development of CNS autoimmunity, suggesting that dural lymphatic vessels do not directly contribute to CNS autoimmunity.
SCIENCE IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Aino Sormunen, Emma Koivulehto, Kari Alitalo, Kalle Saksela, Nihay Laham-Karam, Seppo Ylae-Herttuala
Summary: Traditional Western blotting is commonly used in biological research but has issues with time and reproducibility. Automation, including semi-automated and fully automated systems, offers time-saving and sensitivity advantages. However, the cost of devices and reagents is a downside. Nevertheless, automation can be beneficial for increasing output and facilitating sensitive protein analyses.
METHODS AND PROTOCOLS
(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)