Blood vessels are lined by a single layer of endothelial cells that provide a barrier between circulating plasma and the underlying tissue. Permeability of endothelial cells is tightly regulated, and increased permeability is associated with a number of diseases including atherosclerosis. Endothelial cells are continuously exposed to mechanical forces exerted by flowing blood and are particularly sensitive to shear stress, which is a key determinant of endothelial function. Undisturbed flow promotes endothelial resilience and reduces permeability to macromolecules whereas disturbed flow promotes endothelial dysfunction and barrier disruption. This review will outline recent advances in our understanding of how disturbed and undisturbed flow regulate paracellular and transcellular permeability and will highlight potential cellular targets that could form the basis of therapies to limit the development of cardiovascular disease.
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http://dx.doi.org/10.1016/j.ceb.2023.102213 | DOI Listing |
PLoS One
January 2025
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Triple negative breast cancers often contain higher numbers of tumour-infiltrating lymphocytes compared with other breast cancer subtypes, with their number correlating with prolonged survival. Since little is known about tumour-infiltrating lymphocyte trafficking in triple negative breast cancers, we investigated the relationship between tumour-infiltrating lymphocytes and the vascular compartment to better understand the immune tumour microenvironment in this aggressive cancer type. We aimed to identify mechanisms and signaling pathways responsible for immune cell trafficking in triple negative breast cancers, specifically of basal type, that could potentially be manipulated to change such tumours from immune "cold" to "hot" thereby increasing the likelihood of successful immunotherapy in this challenging patient population.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
ETH Zurich, Department of Biosystems Science and Engineering, Klingelbergstrasse 48, Basel, CH-4056, Switzerland.
Neo-vascularization plays a key role in achieving long-term viability of engineered cells contained in medical implants used in precision medicine. Moreover, strategies to promote neo-vascularization around medical implants may also be useful to promote the healing of deep wounds. In this context, a biocompatible, electroconductive borophene-poly(ε-caprolactone) (PCL) 3D platform is developed, which is called VOLT, to support designer cells engineered with a direct-current (DC) voltage-controlled gene circuit that drives secretion of vascular endothelial growth factor A (VEGFA).
View Article and Find Full Text PDFSci Adv
January 2025
Knight Cancer Precision Biofabrication Hub, Knight Cancer Institute, OHSU, Portland, OR 97201, USA.
A hallmark of chronic and inflammatory diseases is the formation of a fibrotic and stiff extracellular matrix (ECM), typically associated with abnormal, leaky microvascular capillaries. Mechanisms explaining how the microvasculature responds to ECM alterations remain unknown. Here, we used a microphysiological model of capillaries on a chip mimicking the characteristics of healthy or fibrotic collagen to test the hypothesis that perivascular cells mediate the response of vascular capillaries to mechanical and structural changes in the human ECM.
View Article and Find Full Text PDFSci Adv
January 2025
Center for Synaptic Neuroscience and Technology (NSYN@UniGe), Istituto Italiano di Tecnologia, Largo Rosanna Benzi, 10, 16132 Genova, Italy.
The blood-brain barrier (BBB) maintains brain homeostasis but also prevents most drugs from entering the brain. No paracellular diffusion of solutes is allowed because of tight junctions that are made impermeable by the expression of claudin5 (CLDN5) by brain endothelial cells. The possibility of regulating the BBB permeability in a transient and reversible fashion is in strong demand for the pharmacological treatment of brain diseases.
View Article and Find Full Text PDFClin Neuropharmacol
January 2025
Department of Neurosurgery, Yubei District Hospital of TCM, Chongqing, China.
Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy.
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