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Extracellular vesicles stimulate smooth muscle cell migration by presenting collagen VI.

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.

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SUBMITTER: Kapustin A

PROVIDER: S-EPMC10462164 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Matrix-associated extracellular vesicles modulate smooth muscle cell adhesion and directionality by presenting collagen VI.

Kapustin Alexander A Tsakali Sofia Serena SS Whitehead Meredith M Chennell George G Wu Meng-Ying MY Molenaar Chris C Kutikhin Anton A Chen Yimeng Y Ahmad Sadia S Bogdanov Leo L Sinitsky Maxim M Rubina Kseniya K Clayton Aled A Verweij Frederik J FJ Pegtel Dirk Michiel DM Zingaro Simona S Lobov Arseniy A Zainullina Bozhana B Owen Dylan D Parsons Maddy M Parsons Maddy M Cheney Richard E RE Warren Derek D Humphries Martin James MJ Iskratsch Thomas T Holt Mark M Shanahan Catherine M CM

bioRxiv : the preprint server for biology 20250710

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, can 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. Here we show that FN stimulates VSMCs to secrete small extracellular vesicle ...[more]

PMID: 37645762

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