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• W4386001695 abstract "Abstract The extracellular matrix (ECM) supports blood vessel architecture and functionality and undergoes active remodelling during vascular repair and atherogenesis. Vascular smooth muscle cells (VSMCs) are essential for vessel repair and, via their secretome, are able to invade from the vessel media into the intima to mediate ECM remodelling. Accumulation of fibronectin (FN) is a hallmark of early vascular repair and atherosclerosis and here we show that FN stimulates VSMCs to secrete small extracellular vesicles (sEVs) by activating the β1 integrin/FAK/Src pathway as well as Arp2/3-dependent branching of the actin cytoskeleton. Spatially, sEV were secreted via filopodia-like cellular protrusions at the leading edge of migrating cells. We found that sEVs are trapped by the ECM in vitro and colocalise with FN in symptomatic atherosclerotic plaques in vivo . Functionally, ECM-trapped sEVs induced the formation of focal adhesions (FA) with enhanced pulling forces at the cellular periphery. Proteomic and GO pathway analysis revealed that VSMC-derived sEVs display a cell adhesion signature and are specifically enriched with collagen VI. In vitro assays identified collagen VI as playing the key role in cell adhesion and invasion. Taken together our data suggests that the accumulation of FN is a key early event in vessel repair acting to promote secretion of collage VI enriched sEVs by VSMCs. These sEVs stimulate migration and invasion by triggering peripheral focal adhesion formation and actomyosin contraction to exert sufficient traction forces to enable VSMC movement within the complex vascular ECM network. Abstract Figure Figure Abstract Vascular smooth muscle cells sense fibronectin via β1 integrin and secrete small extracellular vesicles loaded with collagen VI via filopodia-like protrusions. These extracellular vesicles are entrapped in the extracellular matrix and induce formation of peripheral focal adhesions. Focal adhesions anchor extracellular matrix to the actin fibrils in the cell. Contraction of the actin fibrils generates the mechanical force for cell locomotion and invasion through the matrix. This figure was created with BioRender( https://biorender.com/ )." @default.
• W4386001695 created "2023-08-20" @default.
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• W4386001695 date "2023-08-18" @default.
• W4386001695 modified "2023-10-07" @default.
• W4386001695 title "Extracellular vesicles stimulate smooth muscle cell migration by presenting collagen VI" @default.
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