Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.
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http://dx.doi.org/10.1016/j.talanta.2024.126415 | DOI Listing |
Commun Biol
January 2025
Freie Universität Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, 14195, Berlin, Germany.
Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal 191201, India.
: Pyroptosis, an inflammatory cell death, is involved in the progression of atherosclerosis. Pyroptosis in endothelial cells (ECs) and its underlying mechanisms in atherosclerosis are poorly understood. Here, we investigated the role of a caspase-4/5-NF-κB pathway in pyroptosis in palmitic acid (PA)-stimulated ECs and EVs as players in pyroptosis.
View Article and Find Full Text PDFHypertension
January 2025
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, China. (F.W., Z.L., W.L., H.L., H.F., S.L., C.Z., Y.Z., S.M., C.W., Z.Z., W.F., J.Z., Q.Y., M.D., W.K., A.L., J.L., X.L., X.W., N.L., Y.C., K.Y., J.W.).
Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.
Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.
Cell Death Dis
January 2025
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.
View Article and Find Full Text PDFNat Cardiovasc Res
January 2025
Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK.
During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state.
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