Background: Angiogenesis is a multi-step process which involves endothelial cell sprouting from existing blood vessels, followed by migration, proliferation, alignment and tube formation. Tetrathiomolybdate (TM) is a multi-hit antiangiogenic agent with actions against multiple angiogenic pathways. These inhibitory effects of TM are attributed to its potent copper level-reducing property. Copper is needed for activation of various angiogenic pathways at the transcriptional and protein levels.
Materials And Methods: The direct effects of TM on angiogenesis of endothelial cells were examined using an in vitro sprout-forming system.
Results: It was shown that depletion of copper by TM selectively repressed bFGF-induced, but not VEGF-induced sprout formation (an early angiogenic step).
Conclusion: This model permitted the separation of VEGF- and bFGF- induced early angiogenesis in vitro, and indicated the existence of mechanistic differences between bFGF- and VEGF- induced early angiogenic events.
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Trends Biotechnol
January 2025
Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands. Electronic address:
Human brain organoids (hBOs) are in vitro, 3D, self-organizing brain tissue structures increasingly used for modeling brain development and disease. Although they traditionally lack vasculature, recent bioengineering developments enable their vascularization, which partly recapitulates neurodevelopmental processes such as neural tube angiogenesis, formation of neurovascular unit (NVU)-like structures, and early barriergenesis. Although vascularized hBOs (vhBOs) are already used to model (defects in) neurovascular development, vascularization efficiency and other outcomes differ substantially between vascularization protocols and overall shortcomings should be considered.
View Article and Find Full Text PDFJ Stroke Cerebrovasc Dis
January 2025
Department of Gerontology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, China. Electronic address:
Objective: Hirudin has shown potential in promoting angiogenesis and providing neuroprotection in ischemic stroke; however, its therapeutic role in promoting cerebrovascular angiogenesis remains unclear. In this study, we aimed to investigate whether hirudin exerts neuroprotective effects by promoting angiogenesis through the regulation of the Wnt/β-catenin signaling pathway.
Methods: An in vitro model of glucose and oxygen deprivation/reperfusion (OGD/R) was established using rat brain microvascular endothelial cells (BMECs).
Cytokine
January 2025
Department of Cardiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address:
Aims: Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Despite the importance of Interleukin 29 (IL-29), a newly identified cytokine of type III interferon family, its role in angiogenesis remains unknown. We aimed to elucidate IL-29's impact on angiogenesis under both and physiological and pathological conditions.
View Article and Find Full Text PDFSci Adv
January 2025
Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT 06511, USA.
Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low shear stress (LSS), physiological shear stress (PSS), high shear stress (HSS), and oscillatory shear stress (OSS) that induce vessel inward remodeling, stabilization, outward remodeling, or disease susceptibility, respectively. Combined with a publicly available database on EC transcriptomic responses to drug treatments, this approach inferred a regulatory network controlling EC states and made several notable predictions.
View Article and Find Full Text PDFAngiogenesis
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Clinical Stem Cell Research Center, Peking University Third Hospital, Peking University, Beijing, 100191, China.
Angiogenesis describes the sprouting of blood vessels from existing vasculatures and it plays a pivotal role in disease progress such as diabetes, age-related macular degeneration and cancer. However, the most widely used anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathway still lacked of specificity and therapeutic efficacy. To establish a method suitable for high-throughput drug screening and faithfully recapitulate the feature of in vivo angiogenesis, we generated a PECAM1-mRuby3-secNluc; ACTA2-EGFP dual reporter human pluripotent stem cell (hPSC) line and utilizing the cell line to establish a visualized and quantifiable in vitro angiogenesis model with stem cell-derived vascular organoid.
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