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The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis. Atheroprone-disturbed flow increases whereas atheroprotective unidirectional shear stress inhibits YAP/TAZ activity. Unidirectional shear stress activates integrin and promotes integrin-Gα interaction, leading to RhoA inhibition and YAP phosphorylation and suppression. YAP/TAZ inhibition suppresses JNK signalling and downregulates pro-inflammatory genes expression, thereby reducing monocyte attachment and infiltration. In vivo endothelial-specific YAP overexpression exacerbates, while CRISPR/Cas9-mediated Yap knockdown in endothelium retards, plaque formation in ApoE mice. We also show several existing anti-atherosclerotic agents such as statins inhibit YAP/TAZ transactivation. On the other hand, simvastatin fails to suppress constitutively active YAP/TAZ-induced pro-inflammatory gene expression in endothelial cells, indicating that YAP/TAZ inhibition could contribute to the anti-inflammatory effect of simvastatin. Furthermore, activation of integrin by oral administration of MnCl reduces plaque formation. Taken together, our results indicate that integrin-Gα-RhoA-YAP pathway holds promise as a novel drug target against atherosclerosis.
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http://dx.doi.org/10.1038/nature20602 | DOI Listing |
Polymers (Basel)
December 2024
Advanced Composites Research Lab, Faculty of Science, Galala University, Galala City 43511, Egypt.
Steel pipeline systems carry about three-quarters of the world's oil and gas. Such pipelines need to be coated to prevent corrosion and erosion. An alternative to the current epoxy-based coating, a multi-layered composite coating is developed in this research.
View Article and Find Full Text PDFPolymers (Basel)
November 2024
Department of Engineering, University of Palermo, Viale Delle Scienze, 90128 Palermo, Italy.
Within the range of composite laminates for structural applications, sandwich laminates are a special category intended for applications characterized by high flexural stresses. As it is well known from the technical literature, structural sandwich laminates have a simple configuration consisting of two skins of very strong material, to which the flexural strength is delegated, between which an inner layer (core) of light material with sufficient shear strength is interposed. As an example, a sandwich configuration widely used in civil, naval, and mechanical engineering is that obtained with fiberglass skins and a core of various materials, such as polyurethane foam or another lightweight material, depending on the application.
View Article and Find Full Text PDFHeliyon
May 2024
Department of Solid Mechanics, Faculty of Mechanical Engineering, University of Kashan, Kashan, P.O. Box 87317-53153, Iran.
Adv Mater
December 2024
Soft Hybrid Materials Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
Stretchable devices, garnering increasing attention as next-generation form factors, have a crucial problem in that vertical contraction occurs during stretching, causing image distortion of stretchable displays and discomfort in skin-attached devices. Previous structural strategies to mitigate vertical contraction, such as auxetic reentrants and wrinkles, suffer from the drawback that their structure becomes visible during stretching. In this study, this issue is addressed by unidirectionally aligning nanoscopic cylinders within block copolymer elastomer films.
View Article and Find Full Text PDFPolymers (Basel)
October 2024
Department of Materials, Textiles and Chemical Engineering (MATCH), Ghent University, Technologiepark 907, B-9052 Zwijnaarde, Belgium.
This study investigates the effectiveness of polyether block amide (PEBA) thermoplastic elastomeric nanofibers in reducing low-velocity impact damage across three carbon fiber composite lay-up configurations: a cross-ply [0°/90°]2s (CP) and a quasi-isotropic [0°/45°/90°/-45°]s (QI) lay-up utilizing unidirectional plies, and a stacked woven [(0°,90°)]4s (W) lay-up using twill woven fabric plies. The flexural strength and interlaminar shear strength of the composites remained unaffected by the addition of nanofibers: around 750 MPa and 63 MPa for CP, 550 MPa and 58 MPa for QI, and 650 MPa and 50 MPa for W, respectively. The incorporation of nanofibers in the interlaminar regions resulted in a substantial reduction in projected damage area, ranging from 30% to 50% reduction over an impact energy range of 5-20 J.
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