Small extracellular vesicles from rat plasma promote migration and proliferation of vascular smooth muscle cells

Abstract

Small extracellular vesicles (sEV) contain various molecules and mediate cell-to-cell communication under both physiological and pathological conditions. We have recently reported that sEV isolated from plasma of normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) regulate systemic blood pressure. The initiation and development of hypertension partly rely on proliferation and migration of vascular smooth muscle cells (SMCs) followed by the structural remodeling of vascular wall. In the present study, we examined the effects of plasma sEV in WKY and SHR on the proliferative and migratory functions of primary rat aortic SMCs. There was no difference in the concentration and size distribution of plasma sEV between WKY and SHR, while the protein expression of CD81 in plasma sEV from SHR was lower than that from WKY. Both plasma sEV from WKY and SHR were internalized into SMCs and stimulated the migration and proliferation with a similar potency. In summary, we, for the first time, demonstrated that plasma sEV in WKY and SHR are physiologically active in terms of proliferative and migratory functions, however, these effects do not seem to be related to the pathogenesis of hypertension development.

Plasma small extracellular vesicles in hypertensive rats impair reactivity of isolated blood vessels

“…It remains to be clarified whether sEV are stable in circulation for 24 hr. We previously confirmed that sEV were uptaken into VSMC within 2 hr [16] and that they were remaining within the cells after 24 hr. Since we focused on the effects of small RNA including microRNA in sEV, which mediates the protein expression in the recipient cells, we examined the long-term effects of sEV.…”

“…sEV were isolated from plasma of WKY (WsEV) and SHR (SsEV) by the precipitation with polyethylene-glycol and ultracentrifugation as previously described [ 15 , 16 ]. WKY and SHR (8-week-old) were deeply anesthetized with urethane (Sigma-Aldrich, St. Louis, MO, USA) (1.5 g/kg, i.p.).…”

“…Particle distribution and concentration of the isolated sEV were measured by a tunable resistive pulse sensing (TRPS) method using a qNANO instrument with an NP150 nanopore at 46.5-47.5 mm stretch (IZON Science, Christchurch, New Zealand) according to the manufacturer's instruction as previously reported [15,16].…”

Autocrine role of senescent cardiac fibroblasts-derived extracellular vesicles

“…The protein expression in NRCFs-derived EV, NRCFs, and NRCMs was determined by Western blotting as previously described [23,25]. After 10 equal amounts of protein were separated by SDS-PAGE (7.5-14%, 80-120 V, 1.5 hr), they were transferred to a nitrocellulose membrane (Pall Corporation, Ann Arbor, MI, USA) (400 mA, 1.5 hr).…”

Reversal of Endothelial Extracellular Vesicle-Induced Smooth Muscle Phenotype Transition by Hypercholesterolemia Stimulation: Role of NLRP3 Inflammasome Activation

“…EVs include three distinct particles such as exosomes, microparticles or microvesicles, and apoptotic bodies ( Noble et al, 2020 ; Swatler et al, 2020 ). Recent studies reported that VSMC proliferation and migration are regulated by EVs derived from ECs ( Ryu et al, 2019 ) as well as from other sources including plasma ( Otani et al, 2020 ), fibroblasts ( Ren et al, 2020 ), macrophages ( Niu et al, 2016 ; Sharma et al, 2018 ), and adipose mesenchymal stem cells ( Liu et al, 2016 ). EVs are known to contain and carry various bioactive molecules, including proteins, lipids, and nucleic acids ( Berezin and Berezin, 2020 ; Xing et al, 2020 ).…”